|
1
|
Lienou LL, Goka MSC, Tagne Simo R, Dongho FFD, Ngono RAN, Rodrigues APR, Telefo PB. Effects of aqueous extract from Cyathula prostrata (Linn.) Blume (Amaranthaceae) on puberty onset and some reproductive parameters in immature female Wistar rats. Hormones (Athens) 2025:10.1007/s42000-025-00633-7. [PMID: 39934557 DOI: 10.1007/s42000-025-00633-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Accepted: 01/28/2025] [Indexed: 02/13/2025]
Abstract
PURPOSE Cyathula prostrata (C. prostrata) a medicinal plant from tropical Africa, is traditionally used in Western Cameroon to treat female infertility. This study investigated the hormone-like effects of the aqueous extract of C. prostrata (AECp) leaves and stems on the onset of puberty and various reproductive parameters in immature female Wistar rats. METHODS Five groups of immature female rats received daily oral doses of AECp for 20 consecutive days. Post-treatment body, ovarian, and uterine weights were recorded, along with uterine and ovarian protein levels, ovarian cholesterol levels, and blood hormone concentrations (FSH, LH, estradiol, and progesterone). RESULTS AECp increased the growth rate in all treated animals. It reduced the age at vaginal opening by 2 to 6 days compared to controls. Secondary and tertiary follicles increased by 32.7% and 37.7%, respectively, in AECp-treated rats (96 mg/kg and 64 mg/kg). AECp significantly reduced uterine and ovarian protein levels by 21.3% and 27.8% at 64 mg/kg dosage. Regardless of dose, AECp lowered ovarian cholesterol and serum FSH levels (p < 0.001). Serum progesterone, estradiol, and LH levels increased significantly at 64 mg/kg compared to controls. CONCLUSION This study demonstrates AECp's positive effects on the onset of puberty and ovarian folliculogenesis in immature female rats.
Collapse
Affiliation(s)
- Landry Lienou Lienou
- Department of Biochemistry, Faculty of Sciences, University of Douala, P.O. Box: 24157, Douala, Cameroon.
| | - Marie Stephanie Chekem Goka
- Research Unit in Medicinal Plants, Food Substances and Nutrition, Department of Biochemistry, Faculty of Science, University of Dschang, P.O. Box 67, Dschang, Cameroon
| | - Richard Tagne Simo
- Department of Biomedical Sciences, University of Ngaoundere, P.O. Box 454, Ngaoundere, Cameroon
| | | | - Rosalie Annie Ngane Ngono
- Department of Biochemistry, Faculty of Sciences, University of Douala, P.O. Box: 24157, Douala, Cameroon
| | | | - Phélix Bruno Telefo
- Research Unit in Medicinal Plants, Food Substances and Nutrition, Department of Biochemistry, Faculty of Science, University of Dschang, P.O. Box 67, Dschang, Cameroon
| |
Collapse
|
|
2
|
Sexual hormones and diabetes: The impact of estradiol in pancreatic β cell. INTERNATIONAL REVIEW OF CELL AND MOLECULAR BIOLOGY 2021. [PMID: 33832654 DOI: 10.1016/bs.ircmb.2021.02.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/13/2023]
Abstract
Diabetes is one of the most prevalent metabolic diseases and its incidence is increasing throughout the world. Data from World Health Organization (WHO) point-out that diabetes is a major cause of blindness, kidney failure, heart attacks, stroke and lower limb amputation and estimated 1.6 million deaths were directly caused by it in 2016. Population studies show that the incidence of this disease increases in women after menopause, when the production of estrogen is decreasing in them. Knowing the impact that estrogenic signaling has on insulin-secreting β cells is key to prevention and design of new therapeutic targets. This chapter explores the role of estrogen and their receptors in the regulation of insulin secretion and biosynthesis, proliferation, regeneration and survival in pancreatic β cells. In addition, delves into the genetic animal models developed and its application for the specific study of the different estrogen signaling pathways. Finally, discusses the impact of menopause and hormone replacement therapy on pancreatic β cell function.
Collapse
|
|
3
|
Effects of the aqueous extract of Dicliptera verticillata on fertility and different stages of gestation in female rats. ZYGOTE 2021; 29:307-313. [PMID: 33653432 DOI: 10.1017/s0967199420000921] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Dicliptera verticillata is a medicinal plant traditionally used in western Cameroon to cure female infertility. This experiment was designed to assess the effects of the aqueous extract of Dicliptera verticillata (AEDv) on fertility and gestation in female rats. Oral increasing doses of AEDv were administered to immature female rats over 20 d. After this time, some animals were mated with fertile males and some fertility parameters were assayed; the other animals were euthanized for preliminary toxicity parameters analysis. The effects of AEDv on the different stages of gestation were assayed on selected animals previously controlled for estrous cycle regularity and mated. AEDv led to an increase in serum, uterine and ovarian proteins as well as in ovarian and uterine weights (P < 0.05) in immature female rats. Hepatic proteins significantly decreased (P < 0.01) in high dose-treated animals (50 and 100 mg/kg) compared with controls. The number of implantation sites and the fertility rate were significantly lower (P < 0.05), while the antifertility activity increased significantly (P < 0.05) in treated rats compared with controls. When administered from the 1st to the 5th day of pregnancy, AEDv led to a decrease of more than 60% in the implantation rate in high dose-treated rats (50, 100, and 400 mg/kg). From the 6th to the 9th day, the implantation, gestation rates and the number of fetuses decreased significantly in all treated groups. From the 11th to the 20th day, a 50% resorption and decrease in gestation rate were reported in 50 mg/kg dose-treated animals. AEDv possesses weak contraceptive and abortifacient effects during pregnancy.
Collapse
|
|
4
|
Slighoua M, Mahdi I, Amrati FEZ, Di Cristo F, Amaghnouje A, Grafov A, Boucetta N, Bari A, Bousta D. Assessment of in vivo estrogenic and anti-inflammatory activities of the hydro-ethanolic extract and polyphenolic fraction of parsley (Petroselinum sativum Hoffm.). JOURNAL OF ETHNOPHARMACOLOGY 2021; 265:113290. [PMID: 32841696 DOI: 10.1016/j.jep.2020.113290] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Revised: 07/28/2020] [Accepted: 08/14/2020] [Indexed: 06/11/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Since the dawn of time, medicinal and aromatic plants (AMPs) represent a precious heritage for humanity, especially in developing countries, who exploit their virtues in traditional pharmacopoeia to cope with health problems such as diabetes, kidney stones, ulcer, and digestive disorders. Petroselinum sativum Hoffm. belongs to Apiaceae family. It is traditionally used to treat arterial hypertension, diabetes, cardiac disease, renal disease, and recently reported as a plant endowed with a female anti-infertility effect. AIM OF THE STUDY This study aims to evaluate the in vivo effect of hydro-ethanolic extract and polyphenols of Petroselinum sativum Hoffm. on cholesterol, protein and estrogen levels, and characterize the chemical composition of polyphenolic fraction. In addition, acute toxicity and anti-inflammatory activity of tested extract was also investigated. MATERIALS AND METHODS Chemical composition of polyphenolic fraction was determined using High-Performance Liquid Chromatography with Diode-Array Detection (HPLC-DAD). First, toxicological investigations including sub-acute toxicity were performed by measuring animals' weights daily for four weeks. Afterwards, histopathological examination of livers and kidneys, and serum assay of ASAT and ALAT were also checked. Next, the acute in vivo anti-inflammatory study of the hydro-ethanolic extract and polyphenols of Petroselinum sativum Hoffm. versus Indomethacin was conducted. Furthermore, we evaluated the estrogenic effect of its hydro-ethanolic extract and the polyphenolic fraction following biochemical assays for the determination of proteins, cholesterol and estrogen levels. RESULTS The results revealed the presence of some phenolic compounds mainly ferulic acid, gallic acid and quercetin. Petroselinum sativum Hoffm. extracts also showed no evidence of hepatotoxicity nor nephrotoxicity, with remarkable anti-inflammatory activity, as well as a significant estrogenic effect compared to negative control. CONCLUSION This study provides a scope of the potential use of Petroselinum sativum Hoffm. extracts in counteracting female infertility issues.
Collapse
Affiliation(s)
- Meryem Slighoua
- Laboratory of Neuroendocrinology and Nutritional and Climatic Environment, University of Sidi-Mohamed-Ben-Abdellah, FSDM, Fez, Morocco.
| | - Ismail Mahdi
- Medical Application Interface Center, Mohammed VI Polytechnic University, Ben-Guerir, Morocco; Laboratory of Microbial Biotechnologies, Agrosciences and Environment (BioMAgE), Faculty of Sciences Semlalia, Cadi Ayyad University, Marrakesh, Morocco
| | - Fatima Ez-Zahra Amrati
- Laboratory of Neuroendocrinology and Nutritional and Climatic Environment, University of Sidi-Mohamed-Ben-Abdellah, FSDM, Fez, Morocco
| | - Francesca Di Cristo
- Elleva Pharma S.R.L Via PietroCastellino, 111-CNR Research Area Naples 1, 80131, Naples, Italy
| | - Amal Amaghnouje
- Laboratory of Neuroendocrinology and Nutritional and Climatic Environment, University of Sidi-Mohamed-Ben-Abdellah, FSDM, Fez, Morocco
| | - Andrey Grafov
- Materials Chemistry Division of the Department of Chemistry at the University of Helsinki, Finland
| | - Nabil Boucetta
- Medical Laboratory Specialized in Medical Biology, Fez, Morocco
| | - Amina Bari
- Biotechnology Laboratory and Preservation of Natural Resources, University of Sidi-Mohamed-Ben-Abdellah, FSDM, Fez, Morocco
| | - Dalila Bousta
- Laboratory of Neuroendocrinology and Nutritional and Climatic Environment, University of Sidi-Mohamed-Ben-Abdellah, FSDM, Fez, Morocco
| |
Collapse
|
|
5
|
Lienou LL, Telefo PB, Rodrigues GQ, Donfack JN, Araújo RA, Bruno JB, Njimou JR, Mbemya TG, Santos RR, Souza JF, Figueiredo JR, Rodrigues APR. Effect of different extracts and fractions of Senecio biafrae (Oliv. &Hiern) J. Moore on in vivo and in vitro parameters of folliculogenesis in experimental animals. JOURNAL OF ETHNOPHARMACOLOGY 2020; 251:112571. [PMID: 31935494 DOI: 10.1016/j.jep.2020.112571] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Revised: 11/26/2019] [Accepted: 01/10/2020] [Indexed: 06/10/2023]
Abstract
BACKGROUND Senecio biafrae is a medicinal plant widely used in traditional medicine to cure female infertility. Some effects have been pharmacologically demonstrated on immature female rats but in vivo and in vitro investigations are still necessary for determining its mechanism of action. The aim of the present study was to evaluate the estrogenic and FSH-like effects of the plant extracts and fractions on some fertility parameters in immature female rats and on in vitro survival and growth of swine preantral follicles. METHODS 21-23 days old female Wistar rats orally received extracts and fractions of S. biafrae at 0, 8 and 64 mg/kg doses over 20 days. The LH, FSH, estradiol and progesterone serum levels were evaluated as well as the ovarian cholesterol, uterus and ovaries masses and proteins. The numbers of follicles at different developmental stages were recorded in ovarian cortexes after histology. Slices of swine ovarian cortexes were cultured along 1 or 7 days in alpha-minimum essential medium (α-MEM) and fixed for morphological analysis of preantral follicles. The fresh control, cultured control (CIV control) and different Senecio biafrae-treated ovarian fragments were analyzed for preantral follicles development. Treatments that showed the best follicle growth in culture were submitted to AgNOR test. The aqueous and MeOH/CH2Cl2 extracts as well as the ethyl acetate and hexane fractions of S. biafrae were submitted to the HPLC for analysis of polyphenolic secondary metabolites. RESULTS Ovarian and uterine proteins were significantly high (p < 0.01) in animals treated with the two dosages of ethyl acetate and n-butanol fractions. The same result was recorded with uterine proteins in animals treated with the hexane fraction. The FSH level significantly dropped with all ethanolic extract doses and with the 64 mg/kg dosage of the methanol/methylene chloride (MeOH/CH2Cl2) extract while LH was reduced (p < 0.01) in almost all the treated groups. Estradiol level was significantly increased (p < 0.001) in the three groups receiving the extracts, but reduced (p < 0.001) in the three groups receiving the fractions of the plant. The progesterone level increased with almost all the treated groups. Primary and secondary follicles augmented (p < 0.01) in MeOH/CH2Cl2 extract and n-butanol fraction while tertiary follicles increased with the same extract and the ethyl acetate fraction (p < 0.05). Treatments with aqueous and ethanolic extracts as well as ethyl acetate fraction led to a significant increase (p < 0.05) in the number of morphologically normal follicles after 7 days of culture as compared to the CIV control. The number of AgNOR dots per follicle was significantly low (p < 0.05) in all cultured groups as compared to the fresh control, except the ethyl acetate 2.8 ng/ml dosage. The same observation was done with AgNOR dots per cell in the 2.8 ng/ml dosage aqueous extract-treated fragments. The phenolic compounds mainly encountered in the plant, independently of the extract or fraction are apigenin, eugenol and rutin. CONCLUSION Extracts and fractions of S. biafrae have an important FSH-like effect which induces follicular survival and growth.
Collapse
Affiliation(s)
- L L Lienou
- University of Dschang, Faculty of Science, Department of Biochemistry, URBPMAN, Dschang, Cameroon; State University of Ceará, Faculty of Veterinary Sciences, LAMOFOPA, Fortaleza, CE, Brazil.
| | - P B Telefo
- University of Dschang, Faculty of Science, Department of Biochemistry, URBPMAN, Dschang, Cameroon.
| | - G Q Rodrigues
- State University of Ceará, Faculty of Veterinary Sciences, LAMOFOPA, Fortaleza, CE, Brazil.
| | - J N Donfack
- State University of Ceará, Faculty of Veterinary Sciences, LAMOFOPA, Fortaleza, CE, Brazil.
| | - R A Araújo
- State University of Ceará, Faculty of Veterinary Sciences, LAMOFOPA, Fortaleza, CE, Brazil.
| | - J B Bruno
- State University of Ceará, Faculty of Veterinary Sciences, LAMOFOPA, Fortaleza, CE, Brazil.
| | - J R Njimou
- University of Ngaoundere, School of Chemical Engineering and Mineral Industries, Ngaoundere, Cameroon.
| | - T G Mbemya
- State University of Ceará, Faculty of Veterinary Sciences, LAMOFOPA, Fortaleza, CE, Brazil.
| | - R R Santos
- Federal University of Pará, Castanhal, Brazil.
| | - J F Souza
- State University of Ceará, Faculty of Veterinary Sciences, LAMOFOPA, Fortaleza, CE, Brazil; Laboratory Brio Genetics and Biotechnology Ltd, Araguaína, TO, Brazil.
| | - J R Figueiredo
- State University of Ceará, Faculty of Veterinary Sciences, LAMOFOPA, Fortaleza, CE, Brazil.
| | - A P R Rodrigues
- State University of Ceará, Faculty of Veterinary Sciences, LAMOFOPA, Fortaleza, CE, Brazil.
| |
Collapse
|
|
6
|
Hudson SB, Kluever BM, Webb AC, French SS. Steroid hormones, energetic state, and immunocompetence vary across reproductive contexts in a parthenogenetic lizard. Gen Comp Endocrinol 2020; 288:113372. [PMID: 31866306 DOI: 10.1016/j.ygcen.2019.113372] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2019] [Revised: 12/17/2019] [Accepted: 12/17/2019] [Indexed: 01/22/2023]
Abstract
Reproduction is energetically expensive and investing in this life history trait is likely accompanied by significant changes in physiological activity. Investment strategy necessary for achieving reproductive success in reptiles can vary with reproductive form and pattern, potentiating different consequences for competing fitness-related traits such as those key to survival. The goal of this study was to assess if and how energetic state (i.e., energy metabolites) and self-maintenance (i.e., immunocompetence) are hormonally modulated across reproductive contexts in an oviparous, parthenogenetic lizard, the Colorado Checkered Whiptail Aspidoscelis neotesselata. Here blood plasma samples were collected from lizards within the US Army Fort Carson Military Installation near Colorado Springs, CO, USA, during seasons of reproductive activity (i.e., June) and inactivity (i.e., August). Measures of reproductive (i.e., estradiol) and energy-mobilizing (i.e., corticosterone) hormones, energy metabolites (i.e., glucose, triglycerides, and free glycerol), and innate immunity (i.e., bactericidal ability) were compared by season and reproductive stage. Levels of energy metabolites and bactericidal ability were compared to levels of E2 and CORT. Bactericidal ability was also compared to levels of energy metabolites. Corticosterone and glucose levels were lower during the reproductive season while triglyceride levels and bactericidal ability were higher, but both estradiol and free glycerol levels did not differ between seasons. Throughout vitellogenesis, corticosterone and glucose levels as well as bactericidal ability did not differ, but estradiol levels were higher during early and mid-stage and both triglyceride and free glycerol levels were lower during gravidity. Corticosterone levels were negatively associated with circulating triglycerides and bactericidal ability, but were not related to glucose nor free glycerol levels. Estradiol levels were positively associated with free glycerol levels and bactericidal ability, but were not related to glucose nor triglyceride levels. Finally, bactericidal ability was negatively associated with glucose, but positively associated with triglycerides. Differences in energetic state and immunocompetence are thus reflected by shifts in hormone secretion across reproductive investment. These findings provide partial support for the hypothesis that energetic state is differentially regulated by steroid hormones to afford reproduction, potentially at the cost of future survival.
Collapse
Affiliation(s)
- S B Hudson
- Department of Biology, Utah State University, Logan, UT 84322-5205, USA; Ecology Center, Utah State University, Logan, UT 84322‑5205, USA.
| | - B M Kluever
- United States Department of Defense, Department of the Army, Directorate of Public Works, Environmental Division, Conservation Branch, Fort Carson, CO 80913, USA; United States Department of Agriculture, Wildlife Services, National Wildlife Research Center, Florida Field Station, Gainesville, FL 32641-6033, USA
| | - A C Webb
- Department of Biology, Utah State University, Logan, UT 84322-5205, USA; Ecology Center, Utah State University, Logan, UT 84322‑5205, USA
| | - S S French
- Department of Biology, Utah State University, Logan, UT 84322-5205, USA; Ecology Center, Utah State University, Logan, UT 84322‑5205, USA
| |
Collapse
|
|
7
|
Han B, Yang Y, Chen J, Tang H, Sun Y, Zhang Z, Wang Z, Li Y, Li Y, Luan X, Li Q, Ren Z, Zhou X, Cong D, Liu Z, Meng Q, Sun F, Pei J. Preparation, Characterization, and Pharmacokinetic Study of a Novel Long-Acting Targeted Paclitaxel Liposome with Antitumor Activity. Int J Nanomedicine 2020; 15:553-571. [PMID: 32158208 PMCID: PMC6986409 DOI: 10.2147/ijn.s228715] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2019] [Accepted: 12/15/2019] [Indexed: 12/16/2022] Open
Abstract
Background Breast cancer is the leading cause of cancer death in women. Chemotherapy to inhibit the proliferation of cancer cells is considered to be the most important therapeutic strategy. The development of long-circulating PEG and targeting liposomes is a major advance in drug delivery. However, the techniques used in liposome preparation mainly involve conventional liposomes, which have a short half-life, high concentrations in the liver and spleen reticuloendothelial system, and no active targeting. Methods Four kinds of paclitaxel liposomes were prepared and characterized by various analytical techniques. The long-term targeting effect of liposomes was verified by fluorescence detection methods in vivo and in vitro. Pharmacokinetic and acute toxicity tests were conducted in ICR mice to evaluate the safety of different paclitaxel preparations. The antitumor activity of ES-SSL-PTX was investigated in detail using in vitro and in vivo human breast cancer MCF-7 cell models. Results ER-targeting liposomes had a particle size of 137.93±1.22 nm and an acceptable encapsulation efficiency of 88.07±1.25%. The liposome preparation is best stored at 4°C, and is stable for up to 48 hrs. Cytotoxicity test on MCF-7 cells demonstrated the stronger cytotoxic activity of liposomes in comparison to free paclitaxel. We used the near-infrared fluorescence imaging technique to confirm that ES-SSL-PTX was effectively targeted and could quickly and specifically identify the tumor site. Pharmacokinetics and acute toxicity in vivo experiments were carried out. The results showed that ES-SSL-PTX could significantly prolong the half-life of the drug, increase its circulation time in vivo, improve its bioavailability and reduce its toxicity and side effects. ES-SSL-PTX can significantly improve the pharmacokinetic properties of paclitaxel, avoid allergic reaction of the original solvent, increase antitumor efficacy and reduce drug toxicity and side effects. Conclusion ES-SSL-PTX has great potential for improving the treatment of breast cancer, thereby improving patient prognosis and quality of life.
Collapse
Affiliation(s)
- Bing Han
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, ChangChun, People's Republic of China
| | - Yue Yang
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, ChangChun, People's Republic of China.,Department of Pharmacy, Ministry of Health Service, Chinese PLA General Hospital, Beijing, People's Republic of China
| | - Jinglin Chen
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, ChangChun, People's Republic of China
| | - Huan Tang
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, ChangChun, People's Republic of China
| | - Yuxin Sun
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, ChangChun, People's Republic of China
| | - Zheng Zhang
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, ChangChun, People's Republic of China
| | - Zeng Wang
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, ChangChun, People's Republic of China
| | - Yan Li
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, ChangChun, People's Republic of China
| | - Yao Li
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, ChangChun, People's Republic of China
| | - Xue Luan
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, ChangChun, People's Republic of China
| | - Qianwen Li
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, ChangChun, People's Republic of China
| | - Zhihui Ren
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, ChangChun, People's Republic of China
| | - Xiaowei Zhou
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, ChangChun, People's Republic of China
| | - Dengli Cong
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, ChangChun, People's Republic of China
| | - Zhiyi Liu
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, ChangChun, People's Republic of China
| | - Qin Meng
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, ChangChun, People's Republic of China
| | - Fei Sun
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, ChangChun, People's Republic of China
| | - Jin Pei
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, ChangChun, People's Republic of China
| |
Collapse
|
|
8
|
Ubiquitination of nuclear receptors. Clin Sci (Lond) 2017; 131:917-934. [PMID: 28473472 DOI: 10.1042/cs20160708] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2016] [Revised: 01/26/2017] [Accepted: 01/31/2017] [Indexed: 12/17/2022]
Abstract
Nuclear receptors (NRs) are cellular proteins, which upon ligand activation, act to exert regulatory control over transcription and subsequent expression. Organized via systemic classification into seven subfamilies, NRs partake in modulating a vast expanse of physiological functions essential for maintenance of life. NRs display particular characteristics towards ubiquitination, the process of addition of specific ubiquitin tags at appropriate locations. Orchestrated through groups of enzymes harboring a diverse array of specialized structural components, the ubiquitination process emphatically alters the fate or downstream effects of NRs. Such influence is especially prominent in transcriptional processes such as promoter clearing for optimization and degradation pathways eliminating or recycling targeted proteins. Ultimately, the ubiquitination of NRs carries significant implications in terms of generating pathological clinical manifestations. Increasing evidence from studies involving patients and disease models suggests a role for ubiquitinated NRs in virtually every organ system. This supports the broad repertoire of roles that NRs play in the body, including modulatory conductors, facilitators, responders to external agents, and critical constituents for pharmacological or biological interventions. This review aims to cover relevant background and mechanisms of NRs and ubiquitination, with a focus towards elucidating subsequent pathophysiology and therapeutics in clinical disorders encompassing such ubiquitinated NRs.
Collapse
|
|
9
|
Differential Effects of Hormones on Cellular Metabolism in Keratoconus In Vitro. Sci Rep 2017; 7:42896. [PMID: 28211546 PMCID: PMC5314412 DOI: 10.1038/srep42896] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2016] [Accepted: 01/18/2017] [Indexed: 12/28/2022] Open
Abstract
Keratoconus (KC) is a corneal thinning disease with an onset commonly immediately post-puberty and stabilization by 40 to 50 years of age. The role of hormones in regulating corneal tissue structure in homeostatic and pathological conditions is unknown. Our group recently linked altered hormone levels to KC. Our current study sought to investigate and delineate the effects of exogenous hormones, such as androgen, luteotropin, and estrogen, on corneal stroma bioenergetics. We utilized our established 3D in vitro model to characterize the effects of DHEA, prolactin, 17β-estradiol on insulin-growth factor-1 and -2 (IGF-1, -2) signaling and metabolic function in primary corneal fibroblasts from healthy controls (HCFs) and KC patients (HKCs). Our data showed that exogenous DHEA significantly downregulated IGF-1 and its receptor in both HCFs and HKCs with HKCs showing consistently lower basal pentose phosphate flux. Prolactin caused no significant change in IGF-1 levels and an increase in IGF-2 in HKCs correlating with an increase in ATP and NADH levels. 17β-estradiol led to a significant upregulation in pentose phosphate flux and glycolytic intermediates in HCFs. Our results identified hormone-specific responses regulated in HKCs compared to HCFs revealing a novel role for hormones on bioenergetics in KC.
Collapse
|
|
10
|
Neuman-Lee LA, French SS. Endocrine-reproductive-immune interactions in female and male Galápagos marine iguanas. Horm Behav 2017; 88:60-69. [PMID: 27818221 DOI: 10.1016/j.yhbeh.2016.10.017] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2016] [Revised: 10/25/2016] [Accepted: 10/28/2016] [Indexed: 12/14/2022]
Abstract
Endocrine-immune interactions are variable across species and contexts making it difficult to discern consistent patterns. There is a paucity of data in non-model systems making these relationships even more nebulous, particularly in reptiles. In the present study, we have completed a more comprehensive test of the relationship among steroid hormones and ecologically relevant immune measures. We tested the relationship between baseline and stress-induced levels of sex and adrenal steroid hormones and standard ecoimmunological metrics in both female and male Galápagos marine iguanas (Amblyrhynchus cristatus). We found significant associations between adrenal activity and immunity, whereby females that mounted greater corticosterone responses to stress had lower basal and stress-induced immunity (i.e., bactericidal ability). Males showed the opposite relationship, suggesting sex-specific immunomodulatory actions of corticosterone. In both sexes, we observed a stress-induced increase in corticosterone, and in females a stress-induced increase in bactericidal ability. Consistent with other taxa, we also found that baseline corticosterone and testosterone in males was inversely related to baseline bactericidal ability. However, in females, we found a positive relationship between both testosterone and progesterone and bactericidal ability. Multivariate analysis did not discern any further endocrine-immune relationships, suggesting that interactions between adrenal, sex steroid hormones, and the immune system may not be direct and instead may be responding to other common stimuli, (i.e., reproductive status, energy). Taken together, these data illustrate significant endocrine-immune interactions that are highly dependent on sex and the stress state of the animal.
Collapse
Affiliation(s)
- Lorin A Neuman-Lee
- Department of Biology, Utah State University, 5305 Old Main Hill, Logan, UT 84322-5305, USA; The Ecology Center, Utah State University, 5205 Old Main Hill, Logan, UT 84322-5205, USA
| | - Susannah S French
- Department of Biology, Utah State University, 5305 Old Main Hill, Logan, UT 84322-5305, USA; The Ecology Center, Utah State University, 5205 Old Main Hill, Logan, UT 84322-5205, USA.
| |
Collapse
|
|
11
|
Lemini C, Hernández A, Jaimez R, Franco Y, Avila ME, Castell A. Morphometric analysis of mice uteri treated with the preservatives methyl, ethyl, propyl, and butylparaben. Toxicol Ind Health 2016; 20:123-32. [PMID: 15941009 DOI: 10.1191/0748233704th202oa] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
The alkyl esters of p-hydroxybenzoic acid (PHBA) known as parabens (Pbens) are widely used as preservatives in food, pharmaceuticals, and cosmetics. Several in vivo and in vitro studies have shown these compounds to be estrogenic. Here, for the first time, we present evidence of their estrogenicity using a morphometric analysis of uteri from mice treated with the preservatives methylparaben (MePben), ethylparaben (EtPben), propylparaben (PrPben), and butylparaben (BuPben) compared with estradiol (E2). Different groups of adult ovariectomized (Ovx) CD1 mice were subcutaneously (sc) treated daily for three days with two different equimolar doses (362 and 1086 mmol/kg) of the Pbens: MePben (55 and 165 mg/kg), EtPben (60 and 180 mg/kg), PrPben (65 and 195 mg/kg), BuPben (70 and 210 mg/kg), E2 (10 mg/kg; 0.036 mmol/kg), and vehicle (propyleneglycol; V, 10 mL/kg). On the fourth day, uteri were dissected, blotted, weighed, and placed in a fixative solution for 24 h. The paraffin embeded uteri were cut to obtain 7 mm thick transversal sections. Luminal epithelium heights (LEH), glandular epithelium heights (GEH), and myometrium widths (MW) were measured. The highest Pbens dose was able to produce uterotrophic effects (38 to 76%) compared to E2 efects (100%). The relative uterotrophic potency to E2 (100) was from 0.02 to 0.009. Significant increases ( P <0.05) in LEH, GEH, and MW as compared with V were obtained: LEH from 87 to 113% (E2 153%), GEH from 10 to 40% (E2 60%), and MW from 35 to 43% (E2 88%). These results confirm that Pbens at the doses assayed here induce estrogenic histological changes in the uteri of Ovx mice.
Collapse
Affiliation(s)
- C Lemini
- Departamento de Farmacología, Facultad de Medicina, UNAM, Ciudad Universitaria, Mexico.
| | | | | | | | | | | |
Collapse
|
|
12
|
Pisani SL, Neese SL, Katzenellenbogen JA, Schantz SL, Korol DL. Estrogen Receptor-Selective Agonists Modulate Learning in Female Rats in a Dose- and Task-Specific Manner. Endocrinology 2016; 157:292-303. [PMID: 26465198 PMCID: PMC4701887 DOI: 10.1210/en.2015-1616] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Estrogens are well known for their enhancing effects on hippocampus-sensitive cognition. However, estrogens can also impair learning and memory, particularly the acquisition of striatum-sensitive tasks. These cognitive shifts appear to be mediated through local estrogen receptor (ER) activation in each neural structure, but little information is known regarding which specific ER subtypes drive the opposing effects on learning. Elucidating the mnemonic roles of discrete ER subtypes is essential for predicting how treatments with distinct ER pharmacology such as drugs, hormone therapies, and phytoestrogen supplements affect cognitive abilities in and thus the daily lives of the women who take them. The present study examined the effects of the ERα-selective compound propyl pyrazole triol and the ERβ-selective compounds diarylpropionitrile and Br-ERb-041 on place and response learning in young adult female rats. Long-Evans rats were ovariectomized and maintained on phytoestrogen-free chow for 3 weeks before behavioral training, with treatments administered via subcutaneous injection 48 and 24 hours before testing. A dose-response paradigm was used, with each compound tested at 4 different doses in separate groups of rats. Propyl pyrazole triol, diarylpropionitrile, and Br-ERb-041 all enhanced place learning and impaired response learning, albeit with distinct dose-response patterns for each compound and task. These results are consistent with the detection of ERα and ERβ in the hippocampus and striatum and suggest that learning is modulated via activation of either ER subtype.
Collapse
Affiliation(s)
- Samantha L Pisani
- Neuroscience Program (S.L.P., S.L.N., S.L.S., D.L.K.) and Department of Chemistry (J.A.K.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61801; Department of Comparative Biosciences (S.L.N., S.L.S.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61802; Department of Psychology and Neuroscience (S.L.N.), Baldwin Wallace University, Berea, Ohio 44017; and Department of Biology (D.L.K.), Syracuse University, Syracuse, New York 13244
| | - Steven L Neese
- Neuroscience Program (S.L.P., S.L.N., S.L.S., D.L.K.) and Department of Chemistry (J.A.K.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61801; Department of Comparative Biosciences (S.L.N., S.L.S.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61802; Department of Psychology and Neuroscience (S.L.N.), Baldwin Wallace University, Berea, Ohio 44017; and Department of Biology (D.L.K.), Syracuse University, Syracuse, New York 13244
| | - John A Katzenellenbogen
- Neuroscience Program (S.L.P., S.L.N., S.L.S., D.L.K.) and Department of Chemistry (J.A.K.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61801; Department of Comparative Biosciences (S.L.N., S.L.S.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61802; Department of Psychology and Neuroscience (S.L.N.), Baldwin Wallace University, Berea, Ohio 44017; and Department of Biology (D.L.K.), Syracuse University, Syracuse, New York 13244
| | - Susan L Schantz
- Neuroscience Program (S.L.P., S.L.N., S.L.S., D.L.K.) and Department of Chemistry (J.A.K.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61801; Department of Comparative Biosciences (S.L.N., S.L.S.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61802; Department of Psychology and Neuroscience (S.L.N.), Baldwin Wallace University, Berea, Ohio 44017; and Department of Biology (D.L.K.), Syracuse University, Syracuse, New York 13244
| | - Donna L Korol
- Neuroscience Program (S.L.P., S.L.N., S.L.S., D.L.K.) and Department of Chemistry (J.A.K.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61801; Department of Comparative Biosciences (S.L.N., S.L.S.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61802; Department of Psychology and Neuroscience (S.L.N.), Baldwin Wallace University, Berea, Ohio 44017; and Department of Biology (D.L.K.), Syracuse University, Syracuse, New York 13244
| |
Collapse
|
|
13
|
Pradhan MA, Blackford JA, Devaiah BN, Thompson PS, Chow CC, Singer DS, Simons SS. Kinetically Defined Mechanisms and Positions of Action of Two New Modulators of Glucocorticoid Receptor-regulated Gene Induction. J Biol Chem 2015; 291:342-54. [PMID: 26504077 DOI: 10.1074/jbc.m115.683722] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2015] [Indexed: 11/06/2022] Open
Abstract
Most of the steps in, and many of the factors contributing to, glucocorticoid receptor (GR)-regulated gene induction are currently unknown. A competition assay, based on a validated chemical kinetic model of steroid hormone action, is now used to identify two new factors (BRD4 and negative elongation factor (NELF)-E) and to define their sites and mechanisms of action. BRD4 is a kinase involved in numerous initial steps of gene induction. Consistent with its complicated biochemistry, BRD4 is shown to alter both the maximal activity (Amax) and the steroid concentration required for half-maximal induction (EC50) of GR-mediated gene expression by acting at a minimum of three different kinetically defined steps. The action at two of these steps is dependent on BRD4 concentration, whereas the third step requires the association of BRD4 with P-TEFb. BRD4 is also found to bind to NELF-E, a component of the NELF complex. Unexpectedly, NELF-E modifies GR induction in a manner that is independent of the NELF complex. Several of the kinetically defined steps of BRD4 in this study are proposed to be related to its known biochemical actions. However, novel actions of BRD4 and of NELF-E in GR-controlled gene induction have been uncovered. The model-based competition assay is also unique in being able to order, for the first time, the sites of action of the various reaction components: GR < Cdk9 < BRD4 ≤ induced gene < NELF-E. This ability to order factor actions will assist efforts to reduce the side effects of steroid treatments.
Collapse
Affiliation(s)
- Madhumita A Pradhan
- From the Steroid Hormones Section, NIDDK/Laboratory of Endocrinology and Receptor Biology
| | - John A Blackford
- From the Steroid Hormones Section, NIDDK/Laboratory of Endocrinology and Receptor Biology
| | | | | | - Carson C Chow
- the Mathematical Biology Section, NIDDK/Laboratory of Biological Modeling, National Institutes of Health, Bethesda, Maryland 20892
| | | | - S Stoney Simons
- From the Steroid Hormones Section, NIDDK/Laboratory of Endocrinology and Receptor Biology,
| |
Collapse
|
|
14
|
Lienou LL, Telefo PB, Njimou JR, Nangue C, Bayala BR, Goka SC, Biapa P, Yemele MD, Donfack NJ, Mbemya JT, Tagne SR, Rodrigues APR. Effect of the aqueous extract of Senecio biafrae (Oliv. & Hiern) J. Moore on some fertility parameters in immature female rat. JOURNAL OF ETHNOPHARMACOLOGY 2015; 161:156-162. [PMID: 25527316 DOI: 10.1016/j.jep.2014.12.014] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/18/2014] [Revised: 10/16/2014] [Accepted: 12/05/2014] [Indexed: 06/04/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Senecio biafrae is a plant from the huge family of Asteraceae used in the African pharmacopoeia for the treatment of many ailments among which is infertility. MATERIAL AND METHODS The aqueous extract, which was primarily subjected to polyphenol analysis, has been administered to immature female rats for 20 days at 8, 32, 64 and 128 mg/kg of body weight. The day following the treatment, the animals were sacrificed; their serum, ovary and uterus were retained respectively for reproductive hormones, ovarian and uterine proteins, and ovarian cholesterol assays. RESULTS Light body weight gain variation of treated animals was observed during the experimental period. A significant increase (p ˂ 0.05) in serum estradiol and proteins as well as in uterine weight (p ˂ 0.01) of all Senecio biafrae treated animals was noted. No significant variation was noticed in the ovarian weight and follicle numbers. CONCLUSION The various biochemical and physiological parameters of fertility were significantly improved with the aqueous extract of Senecio biafrae, thus attesting some of its traditional usage.
Collapse
Affiliation(s)
- L L Lienou
- University of Dschang, Faculty of Science, Department of Biochemistry, P.O Box: 67 Dschang, Cameroon
| | - P B Telefo
- University of Dschang, Faculty of Science, Department of Biochemistry, P.O Box: 67 Dschang, Cameroon.
| | - J R Njimou
- University of Yaounde I: Analytical Chemistry Laboratory Inorganic Chemistry Department, Faculty of Sciences, P.O Box 812, Yaounde, Cameroon
| | - C Nangue
- Pathological Analysis Department of the Central Hospital of Yaounde, Cameroon
| | - B R Bayala
- University of Ouagadougou, UFR/SVT, Laboratory of Animal Physiology, 03P.O. Box 7021 Ouagadougou 03, Burkina Faso
| | - S C Goka
- University of Dschang, Faculty of Science, Department of Biochemistry, P.O Box: 67 Dschang, Cameroon
| | - P Biapa
- University of Dschang, Faculty of Science, Department of Biochemistry, P.O Box: 67 Dschang, Cameroon
| | - M D Yemele
- University of Dschang, Faculty of Science, Department of Biochemistry, P.O Box: 67 Dschang, Cameroon
| | - N J Donfack
- State University of Céara, Faculty of Veterinary Sciences, LAMOFOPA, Fortaleza, Brazil
| | - J T Mbemya
- University of Dschang, Faculty of Science, Department of Biochemistry, P.O Box: 67 Dschang, Cameroon
| | - S R Tagne
- University of Dschang, Faculty of Science, Department of Biochemistry, P.O Box: 67 Dschang, Cameroon
| | - A P R Rodrigues
- State University of Céara, Faculty of Veterinary Sciences, LAMOFOPA, Fortaleza, Brazil
| |
Collapse
|
|
15
|
Principi M, Barone M, Pricci M, De Tullio N, Losurdo G, Ierardi E, Di Leo A. Ulcerative colitis: from inflammation to cancer. Do estrogen receptors have a role? World J Gastroenterol 2014; 20:11496-11504. [PMID: 25206257 PMCID: PMC4155343 DOI: 10.3748/wjg.v20.i33.11496] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2014] [Revised: 03/29/2014] [Accepted: 05/23/2014] [Indexed: 02/06/2023] Open
Abstract
Ulcerative colitis (UC) is a condition at increased risk for colorectal carcinoma (CRC) development. Nowadays, screening and follow-up programs are routinely performed worldwide to promote the early detection of CRCs in subjects with well known risk factors (extent, duration and severity of the disorder). The diffusion of these procedures is presumably the main reason for the marked reduction of cancer incidence and mortality in the course of UC. In addition, chemoprevention has been widely investigated and developed in many medical fields, and aspirin has shown a preventive effect against CRC, while mesalazine has been strongly invoked as a potential chemopreventive agent in UC. However, available studies show some limitations due to the obvious ethical implications of drug withdrawal in UC in order to design a control group. The estrogen receptors (ER) alpha/beta balance seems to have a relevant influence on colorectal carcinogenesis and ER beta appears to parallel apoptosis, and hence an anti-carcinogenic effect. Phytoestrogens are compounds acting as ER beta agonists and have shown a promising chemopreventive effect on sporadic as well as genetically inherited CRC. There is evidence suggesting a role for ERs in UC-related carcinogenesis. In this perspective, since these substances can be considered as dietary supplements and are completely free from side effects, phytoestrogens could be an interesting option for CRC prevention, even when the disease is a consequence of long-term chronic inflammation, as in the course of UC. Further studies of their effects are warranted in both the basic research and clinical fields.
Collapse
|
|
16
|
Gaete L, Tchernitchin AN, Bustamante R, Villena J, Lemus I, Gidekel M, Cabrera G, Astorga P. Daidzein-estrogen interaction in the rat uterus and its effect on human breast cancer cell growth. J Med Food 2012; 15:1081-90. [PMID: 23216111 PMCID: PMC3523250 DOI: 10.1089/jmf.2011.0322] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2011] [Accepted: 07/20/2012] [Indexed: 11/12/2022] Open
Abstract
Sex hormone replacement therapy provides several advantages in the quality of life for climacteric women. However, estrogen-induced cell proliferation in the uterus and mammary gland increases the risk of cancer development in these organs. The lower incidence of mammary cancer in Asian women as compared with Western women has been attributed to high intake of soy isoflavones, including genistein. We have previously shown that genistein induces an estradiol-like hypertrophy of uterine cells, but does not induce cell proliferation, uterine eosinophilia, or endometrial edema. It also inhibits estradiol-induced mitosis in uterine cells and hormone-induced uterine eosinophilia and endometrial edema. Nevertheless, genistein stimulates growth of human breast cancer cells in culture; therefore, it is not an ideal estrogen for use in hormone replacement therapy (HRD). The present study investigated the effect of another soy isoflavone, daidzein (subcutaneous, 0.066 mg/kg body weight), in the same animal model, and its effect on responses induced by subsequent treatment (1 h later) with estradiol-17β (E(2); subcutaneous, 0.33 mg/kg body weight). In addition, we investigated the effects of daidzein (1 μg/mL) or E(2) on the growth of human breast cancer cells in culture. Results indicate that daidzein stimulates growth of breast cancer cells and potentiates estrogen-induced cell proliferation in the uterus. We suggest caution for the use of daidzein or formulas containing this compound in HRD. Future research strategies should be addressed in the search for new phytoestrogens that selectively inhibit cell proliferation in the uterus and breast.
Collapse
Affiliation(s)
- Leonardo Gaete
- Institute of Biomedical Sciences (ICBM), School of Medicine, University of Chile, Santiago, Chile
| | - Andrei N. Tchernitchin
- Institute of Biomedical Sciences (ICBM), School of Medicine, University of Chile, Santiago, Chile
| | - Rodrigo Bustamante
- Institute of Biomedical Sciences (ICBM), School of Medicine, University of Chile, Santiago, Chile
| | - Joan Villena
- School of Medicine, Universidad de Valparaiso, Valparaiso, Chile
| | - Igor Lemus
- School of Chemical and Pharmaceutical Sciences, University of Chile, Santiago, Chile
| | | | | | - Paola Astorga
- Institute of Biomedical Sciences (ICBM), School of Medicine, University of Chile, Santiago, Chile
| |
Collapse
|
|
17
|
Hill RJ, Billas IML, Bonneton F, Graham LD, Lawrence MC. Ecdysone receptors: from the Ashburner model to structural biology. ANNUAL REVIEW OF ENTOMOLOGY 2012; 58:251-271. [PMID: 23072463 DOI: 10.1146/annurev-ento-120811-153610] [Citation(s) in RCA: 102] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/01/2023]
Abstract
In 1974, Ashburner and colleagues postulated a model to explain the control of the puffing sequence on Drosophila polytene chromosomes initiated by the molting hormone 20-hydroxyecdysone. This model inspired a generation of molecular biologists to clone and characterize elements of the model, thereby providing insights into the control of gene networks by steroids, diatomic gases, and other small molecules. It led to the first cloning of the EcR subunit of the heterodimeric EcR-USP ecdysone receptor. X-ray diffraction studies of the ligand-binding domain of the receptor are elucidating the specificity of receptor-ecdysteroid interactions, the selectivity of some environmentally friendly insecticides, the evolution of the EcR-USP heterodimer, and indeed Ashburner's classical biochemical evidence for the central role of the ecdysone receptor in his model.
Collapse
Affiliation(s)
- Ronald J Hill
- CSIRO Animal, Food and Health Sciences, North Ryde, NSW 2113, Australia.
| | | | | | | | | |
Collapse
|
|
18
|
Lienou LL, Telefo BP, Bale B, Yemele D, Tagne RS, Goka SC, Lemfack CM, Mouokeu C, Moundipa PF. Effect of the aqueous extract of Senecio biafrae (Oliv. & Hiern) J. Moore on sexual maturation of immature female rat. Altern Ther Health Med 2012; 12:36. [PMID: 22482701 PMCID: PMC3350434 DOI: 10.1186/1472-6882-12-36] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2011] [Accepted: 04/06/2012] [Indexed: 12/29/2022]
Abstract
Background Senecio biafrae (Asteraceae) is a medicinal plant widely used by traditional healers in the western region of Cameroon for the treatment of female infertility. This experiment was designed to evaluate the effect of the aqueous extract from leaves and stems of S. biafrae (AESb) on the onset of puberty and some biochemical and physiological parameters of reproduction in immature Wistar female rats. Methods Different doses of AESb were daily and orally administered to immature female rats (13 animals/group) for 30 days. At the end of the treatment period, six animal of each experimental group were sacrificed and their body, ovarian, uterus weight; uterine, ovarian protein or cholesterol level as well as data on puberty onset recorded. The remaining animals of each group were used for the fertility test and some gestational parameters recorded. Results A linear increase in the growth rate of all animals was observed. The body weight gain in animals treated at the dose of 8 mg/kg of AESb significantly increased (p < 0.05) after 25 days of treatment while those receiving the doses of 32 and 64 mg/kg presented a significantly low body weight gain starting from the 19th day till the end of the treatment period. The ages (days) of animals at vaginal opening (VO) was significantly reduced (p < 0.05) in those treated with the doses of 32 (41.25 ± 0.51) and 64 mg/kg (41.42 ± 0.54) as compared to control animals (43.33 ± 0.73). AESb significantly increased (p < 0.05) the ovarian weight and the number of corpora lutea in animals treated with 8 mg/kg as well as the uterine weight and protein levels irrespective of the dose. No significant effect of the extract on various fertility and gestational parameters was registered. Conclusion The overall results of the present study provide evidence on the puberty onset induction and ovarian folliculogenesis effect of AESb in immature female rat.
Collapse
|
|
19
|
Gaughan EM, Come SE. Optimizing Endocrine Therapy for Metastatic Breast Cancer. CURRENT BREAST CANCER REPORTS 2012. [DOI: 10.1007/s12609-011-0063-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
|
|
20
|
Telefo PB, Tagne SR, Koona OES, Yemele DM, Tchouanguep FM. Effect of the aqueous extract of Justicia insularis T. Anders (Acanthaceae) on ovarian folliculogenesis and fertility of female rats. AFRICAN JOURNAL OF TRADITIONAL, COMPLEMENTARY, AND ALTERNATIVE MEDICINES : AJTCAM 2011; 9:197-203. [PMID: 23983335 PMCID: PMC3746622 DOI: 10.4314/ajtcam.v9i2.3] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Justicia insularis T. Anders (Acanthaceae) is a medicinal plant whose leaves and those of three other plants are mixed for the preparation of a concoction used to improve fertility and to reduce labour pains in women of the Western Region of Cameroon. Previous studies have demonstrated the inducing potential on ovarian folliculogenesis and steroidogenesis of the aqueous extract of the leaf mixture (ADHJ) of four medicinal plants (Aloe buettneri, Dicliptera verticillata, Hibiscus macranthus and Justicia insularis) among which the later represented the highest proportion. This study was aimed at evaluating the ovarian inducing potential of J. insularis in immature female rats. Various doses of the aqueous extract of J. insularis were daily and orally given, for 20 days, to immature female rats distributed into four experimental groups of twenty animals each. At the end of the experimental period some biochemical and physiological parameters of ovarian function were assayed. The administration of the aqueous extract of Justicia insularis significantly induced an early vaginal opening in all treated groups (P < 0.001) as well as an increase (at doses of 50 or 100 mg/kg) in the number of hemorrhagic points, Corpus luteum, implantation sites, ovarian weight, uterine and ovarian proteins. Ovarian cholesterol level (P < 0.05) significantly decreased in animals treated with the lowest dose (12.5 mg/kg). The evaluation of the toxicological effects of the extract on pregnancy showed that it significantly increased pre- and post-implantation losses, resorption index and decreased the rate of nidation as well as litter's weight. These results suggest that the aqueous extract of Justicia insularis induces ovarian folliculogenesis thus justifying its high proportion in the leaf mixture of ADHJ.
Collapse
Affiliation(s)
- Phelix Bruno Telefo
- University of Dschang, Faculty of Science, Laboratory of Biochemistry of Medicinal Plants, Food and Nutritional Science P.O. Box: 67 Dschang, Cameroon.
| | | | | | | | | |
Collapse
|
|
21
|
Gaete L, Tchernitchin AN, Bustamante R, Villena J, Lemus I, Gidekel M, Cabrera G, Carrillo O. Genistein selectively inhibits estrogen-induced cell proliferation and other responses to hormone stimulation in the prepubertal rat uterus. J Med Food 2011; 14:1597-603. [PMID: 21612459 DOI: 10.1089/jmf.2010.0349] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Sex hormone replacement therapy helps improve quality of life in climacteric women. However, estrogen-induced cell proliferation in the uterus and mammary gland increases the risk for cancer in these organs. The lower incidence of mammary cancer in Asian women than in western women has been attributed to high intake of soy isoflavones, including genistein. Our previous work in the prepubertal rat uterus model showed that genistein (0.5 mg/kg body weight subcutaneously) caused an estradiol-like hypertrophy in myometrial and uterine luminal epithelial cells and an increase in RNA content in luminal epithelium; however, it did not induce cell proliferation, uterine eosinophilia, or endometrial edema. The present study investigated, in the same animal model, the effect of genistein administration (0.5 mg/kg body weight subcutaneously) before treatment with estradiol-17β (0.33 mg/kg body weight subcutaneously) on uterine responses that were not induced by genistein. Pretreatment with this phytoestrogen completely inhibited estradiol-induced mitoses in uterine luminal epithelium, endometrial stroma, and myometrium and partially inhibited estradiol-induced uterine eosinophilia and endometrial edema. These findings indicate that genistein protects against estrogen-induced cell proliferation in the uterus and suggest that future studies should investigate the possibility of using this agent to decrease the risk for uterine cancer after hormone replacement therapy in climacteric women.
Collapse
Affiliation(s)
- Leonardo Gaete
- 1Laboratory of Experimental Endocrinology and Environmental Pathology, Institute of Biomedical Sciences (ICBM), University of Chile Medical School, Santiago, Chile
| | | | | | | | | | | | | | | |
Collapse
|
|
22
|
Oehler S, Müller-Hill B. High local concentration: a fundamental strategy of life. J Mol Biol 2009; 395:242-53. [PMID: 19883663 DOI: 10.1016/j.jmb.2009.10.056] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2009] [Revised: 10/22/2009] [Accepted: 10/27/2009] [Indexed: 12/26/2022]
Abstract
Local increase in concentration is a basic principle of transcriptional control. Closer inspection reveals that it is a major force governing all interactions within and between proteins and DNA. Local increase in concentration acts on all levels of organization of living matter. The structures and functions of two central molecules of life-the linear polymers DNA and protein-are particularly illuminating examples. Local increase in concentration leads to cooperative or competitive interactions between molecules. It is an important principle of life.
Collapse
Affiliation(s)
- Stefan Oehler
- Biomedical Sciences Research Center Alexander Fleming, 34 Fleming Street, GR-16672 Vari, Greece.
| | | |
Collapse
|
|
23
|
Jaffer S, Shynlova O, Lye S. Mammalian target of rapamycin is activated in association with myometrial proliferation during pregnancy. Endocrinology 2009; 150:4672-80. [PMID: 19589861 DOI: 10.1210/en.2009-0419] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The adaptive growth of the uterus during gestation involves gradual changes in cellular phenotypes from the early proliferative to the intermediate synthetic phase of cellular hypertrophy, ending in the final contractile/labour phenotype. The mammalian target of rapamycin (mTOR) signaling pathway regulates cell growth and proliferation in many tissues. We hypothesized that mTOR was a mediator of hormone-initiated myometrial hyperplasia during gestation. The protein expression and phosphorylation levels of mTOR, its upstream regulators [insulin receptor substrate-1, phosphoinositide-3-kinase (PI3K), Akt], and downstream effectors [S6-kinase-1 (S6K1) and eI4FE-binding protein 1 (4EBP1)] were analyzed throughout normal pregnancy in rats. In addition, we used an ovariectomized (OVX) rat model to analyze the modulation of the mTOR pathway and proliferative activity of the uterine myocytes by estradiol alone and in combination with the mTOR-specific inhibitor rapamycin. Our results demonstrate that insulin receptor substrate-1 protein levels and the phosphorylated (activated) forms of PI3K, mTOR, and S6K1 were significantly up-regulated in the rat myometrium during the proliferative phase of pregnancy. Treatment of the OVX rats with estradiol caused a transient increase in IGF-I followed by an up-regulation of the PI3K/mTOR pathway, which became apparent by a cascade of phosphorylation reactions (P-P85, P-Akt, P-mTOR, P-S6K1, and P-4EBP1). Rapamycin blocked activation of P-mTOR, P-S6K1, and P-4EBP1 proteins and significantly reduced the number of proliferating cells in the myometrium of OVX rats. Our in vivo data demonstrate that estradiol was able to activate the PI3K/mTOR signaling pathway in uterine myocytes and suggest that this activation is responsible for the induction of myometrial hyperplasia during early gestation.
Collapse
Affiliation(s)
- Shabana Jaffer
- Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
| | | | | |
Collapse
|
|
24
|
Trevisi M, Ricci D, Mazzoni M. Ultrastructural Observations on the Guinea Pig Epithelium in the Vestibular Apparatus during Steroid Hormone Treatment. Acta Otolaryngol 2009. [DOI: 10.3109/00016488009136998] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
|
|
25
|
Castañeda E, Liao S. A New Method for the Characterization of the Androgen Receptors by use of a Steroid Antibody. ACTA ACUST UNITED AC 2009. [DOI: 10.3109/07435807409088993] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
|
|
26
|
Milanesi L, de Boland AR, Boland R. Expression and localization of estrogen receptor α in the C2C12 murine skeletal muscle cell line. J Cell Biochem 2008; 104:1254-73. [DOI: 10.1002/jcb.21706] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
|
|
27
|
Abstract
The hormonal control of implantation in mammalian species with and without embryonic diapause is described. In a majority of species displaying the obligate form of diapause the corpora lutea appear to exhibit a low level of steroidogenic activity throughout diapause, full luteal activity being resumed just before the initiation of implantation. Fluctuations in the plasma levels of oestrogen and progesterone during diapause may serve to prime the uterus for implantation. In species exhibiting the facultative form of diapause, such as the rat and mouse, both progesterone and nidatory oestrogen are required for the induction of implantation. In species not displaying embryonic diapause implantation will take place in the presence of progesterone alone. In the light of these considerations the selection of animal models for drug-screening purposes and possible new approaches to contraception are discussed.
Collapse
|
|
28
|
Tsukahara K, Kakuo S, Moriwaki S, Hotta M, Ohuchi A, Kitahara T, Harada N. The characteristics of aromatase deficient hairless mice indicate important roles of extragonadal estrogen in the skin. J Steroid Biochem Mol Biol 2008; 108:82-90. [PMID: 17951050 DOI: 10.1016/j.jsbmb.2007.07.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2007] [Accepted: 07/12/2007] [Indexed: 11/17/2022]
Abstract
The roles of extragonadal estrogen in the skin are poorly understood, due to the lack of proper animal models. We examined the skin phenotypes of aromatase-knockout hairless (ArKO) mice and wild-type hairless (WT) mice, both of which were obtained through crossbreeding of Ar+/- mice and hairless mice. Differences in the skins of ArKO and WT mice were compared with those of ovariectomized (OVX) and control (Sham) mice. A difference was observed in the skin tone of ArKO mice, which is pale white and differs from the pinkish tone of all other mice. However, both ArKO and OVX mice similarly exhibited deteriorations of skin properties as compared to their respective controls. Furthermore, all the deteriorations were similarly amplified by chronic UVB irradiation in both ArKO and OVX mice as compared to their respective controls. The unique skin phenotype of ArKO mice was observed in sunburn reactions. Specifically, skins of ArKO mice showed no reaction after an acute UVB irradiation at dose intensities caused sunburn in others. However, follow-up observation found delayed reactions associated with brownish skin color and swelling only in ArKO mice, thereby suggesting that the role of extragonadal estrogen may be connected with the protective reactions of skin.
Collapse
Affiliation(s)
- Kazue Tsukahara
- Biological Science Laboratories, Kao Corporation, Ichikai, Haga, Tochigi, Japan
| | | | | | | | | | | | | |
Collapse
|
|
29
|
Fjøsne HE, Jacobsen AB, Lundgren S. Adjuvant cyclic Tamoxifen and Megestrol acetate treatment in postmenopausal breast cancer patients – Longterm follow-up. Eur J Surg Oncol 2008; 34:6-12. [PMID: 17881183 DOI: 10.1016/j.ejso.2007.07.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2007] [Accepted: 07/02/2007] [Indexed: 10/22/2022] Open
Abstract
AIMS To evaluate possible differences in effect on recurrence-free survival (RFS) and overall survival (OS) in node positive postmenopausal breast cancer patients receiving Tamoxifen or cyclic Tam and Megestrol acetate as adjuvant treatment. METHODS Between 1989 and 1994, 489 patients with pT(1-2)pN+ hormone receptor positive or unknown tumours were included in a randomized national multicenter study to receive either Tam alone or cyclic Tam (8 weeks) and MA (8 weeks) for 2 years. Final follow-up was completed as of June 2002. Time from start of treatment to first recurrence and novel primary breast tumour, overall survival and cancer specific survival were estimated. RESULTS No differences in RFS, OS or cancer specific survival were observed between the two treatment groups. CONCLUSIONS Adjuvant treatment used as standard Tam alone, compared to Tam and MA, as employed in this group of patients gave similar outcomes. Side effects that led to cessation of study medication were observed in both arms.
Collapse
Affiliation(s)
- H E Fjøsne
- Breast and Endocrine Unit, Department of Surgery, St. Olavs University Hospital, N-7006 Trondheim, Norway.
| | | | | |
Collapse
|
|
30
|
Pilka R, Oborna I, Lichnovsky V, Havelka P, Fingerova H, Eriksson P, Hansson S, Casslén B. Endometrial expression of the estrogen-sensitive genes MMP-26 and TIMP-4 is altered by a substitution protocol without down-regulation in IVF patients. Hum Reprod 2006; 21:3146-56. [PMID: 17012332 DOI: 10.1093/humrep/del180] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND The aim of this study was to analyse the effects of an estradiol (E(2))-progesterone substitution protocol on the endometrial expression of estrogen-sensitive genes during the peri-implantation period. METHODS Peripheral blood and endometrial biopsies were obtained from 13 infertile women both in a natural cycle (NC), on days 5 and 7 after ovulation (NC5, NC7), and in an artificial (substituted) cycle (AC), on days 5 and 7 of progesterone addition (AC5, AC7). Estrogen receptor-alpha (ERalpha) and progesterone receptor (PR) were assayed by immunohistochemistry. Matrix metalloproteinase-26 (MMP-26) mRNA and tissue inhibitor of metalloproteinase-4 (TIMP-4) mRNA were semiquantitatively assessed in tissue sections using in situ hybridization (ISH) and quantified in tissue extracts using real-time PCR. RESULTS Levels of both E(2) and progesterone were higher in the peripheral blood in AC than in NC. Also on day AC5, expressions of ERalpha, PR and MMP-26 mRNA (focally) were increased in the epithelium and TIMP-4 mRNA in the stroma. Expression levels of these genes dropped significantly between AC5 and AC7, but not between NC5 and NC7. Abnormally high levels in AC5 samples suggest overstimulation with E(2), and the rapid decrease between AC5 and AC7 suggests overstimulation with progesterone. CONCLUSIONS In ACs, increased levels of E(2) in the blood exaggerate the endometrial expression of estrogen-sensitive genes, whereas higher levels of progesterone in the blood in the secretory phase exaggerate the drop in expression of these genes. Dramatic variations in the gene expression may not be optimal for the implantation process.
Collapse
Affiliation(s)
- R Pilka
- Department of Obstetrics and Gynaecology, Palacky University, Olomouc, Czech Republic
| | | | | | | | | | | | | | | |
Collapse
|
|
31
|
Nicolini A, Giardino R, Carpi A, Ferrari P, Anselmi L, Colosimo S, Conte M, Fini M, Giavaresi G, Berti P, Miccoli P. Metastatic breast cancer: an updating. Biomed Pharmacother 2006; 60:548-56. [PMID: 16950593 DOI: 10.1016/j.biopha.2006.07.086] [Citation(s) in RCA: 91] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2006] [Accepted: 07/28/2006] [Indexed: 01/09/2023] Open
Abstract
UNLABELLED This article reports on recent advances on metastatic breast cancer. Detection, prognostic factors, predictors of response to therapy and therapy, with particular regard to targeted therapies, were examined. DETECTION Unlike current guidelines that yet do not routinely recommend intensive clinical-instrumental post-operative follow-up of breast cancer patients, relatively large data collected in the last decades have shown that an intensive post-operative follow-up with 'dynamic evaluation' of a suitable tumour marker panel precedes a few months as average the clinical and/or instrumental sign of a pending relapse in most relapsed patients and largely limits the use of the common instrumental examinations. PROGNOSIS AND THERAPY PREDICTORS Disease-free interval (DFI)<or=24 months, adjuvant chemotherapy, liver and distant soft tissue involvement or DFI>24 months and disease confined to bony skeleton are prognostic factors more often correlated with relatively poor or prolonged survival, respectively. Estrogen receptor (ER) expression in primary tumour and at the relapse correlates strongly with response to salvage hormone therapy and data from large trials showed that 38-59% of ER and/or PR+ post-menopausal patients had clinical benefit from first line tamoxifen or aromatase inhibitors. An inverse correlation of ER with epidermal growth factor receptor (EGFR) has been found. The co-expression of HER-2/neu and/or elevated serum HER-2/neu protein level were associated with a low rate and shorter duration of response of ER+ patients to first line hormone therapy. Accordingly, ER-EGFR- compared with ER-EGFR+ tumours are usually more responsive to endocrine therapy. High class III beta-tubulin expression or fall in insulin-like growth factor binding protein-3 (IGFBP-3) from baseline levels have been found to significantly predict resistance to chemotherapeutic agents. THERAPY Liposomes as carrier of doxorubicin (Caelix, Evacet, Myocet) is one approach to decrease the anthracycline-related cardiac toxicity. Weekly paclitaxel or docetaxel and oral formulation of vinorelbine and 5-fluorouracil (5-FU) (capecitabine) provide new effective and well tolerated options that reach greater dose intensity and cumulative dose than with the conventional schedules. As to the so called 'tailored' or targeted therapies, the more potent and highly selective third generation of aromatase inhibitors (letrozole, anastrozole, exemestane) targeting ER+ tumours by estrogen deprivation, challenge tamoxifen as current standard first line therapy in postmenopausals. One pilot study showed that stimulation of cellular immunity by the addition of beta-interferon-interleukin-2 sequence in patients on clinical benefit on first line tamoxifen significantly prolonged median overall survival (OS) and duration of response compared to that observed in similar patients only treated with tamoxifen. Trastuzumab, a humanised monoclonal antibody to extracellular domain of HER-2, plus conventional chemotherapy has become a standard of care for women with overexpressing HER-2 tumours. Bevacizumab is a recombinant humanised monoclonal antibody to vascular endothelial growth factor (VEGF) that in refractory metastatic breast cancer doubled the response rate of capecitabine although it did not affect survival. Finally, the so called 'oligometastatic' and a few stage IV diseases are conditions amenable to be rendered with no evidence of disease (NED) after local surgery and/or radiation. In both, as well as in complete responders to chemotherapy, minimal residual disease (m.r.d.) likely continues to be present. Recent data suggest that 'biological' therapy (immunomodulators and/or retinoids with or without hormone therapy), might be suitable to be successfully tested in these patients as maintenance treatment given soon after local intervention or chemotherapy.
Collapse
Affiliation(s)
- A Nicolini
- Department of Internal Medicine, University of Pisa, via Roma 67, 56126 Pisa, Italy.
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
32
|
Birzniece V, Bäckström T, Johansson IM, Lindblad C, Lundgren P, Löfgren M, Olsson T, Ragagnin G, Taube M, Turkmen S, Wahlström G, Wang MD, Wihlbäck AC, Zhu D. Neuroactive steroid effects on cognitive functions with a focus on the serotonin and GABA systems. BRAIN RESEARCH REVIEWS 2006; 51:212-239. [PMID: 16368148 DOI: 10.1016/j.brainresrev.2005.11.001] [Citation(s) in RCA: 106] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/01/2005] [Revised: 11/10/2005] [Accepted: 11/11/2005] [Indexed: 01/20/2023]
Abstract
This article will review neuroactive steroid effects on serotonin and GABA systems, along with the subsequent effects on cognitive functions. Neurosteroids (such as estrogen, progesterone, and allopregnanolone) are synthesized in the central and peripheral nervous system, in addition to other tissues. They are involved in the regulation of mood and memory, in premenstrual syndrome, and mood changes related to hormone replacement therapy, as well as postnatal and major depression, anxiety disorders, and Alzheimer's disease. Estrogen and progesterone have their respective hormone receptors, whereas allopregnanolone acts via the GABA(A) receptor. The action of estrogen and progesterone can be direct genomic, indirect genomic, or non-genomic, also influencing several neurotransmitter systems, such as the serotonin and GABA systems. Estrogen alone, or in combination with antidepressant drugs affecting the serotonin system, has been related to improved mood and well being. In contrast, progesterone can have negative effects on mood and memory. Estrogen alone, or in combination with progesterone, affects the brain serotonin system differently in different parts of the brain, which can at least partly explain the opposite effects on mood of those hormones. Many of the progesterone effects in the brain are mediated by its metabolite allopregnanolone. Allopregnanolone, by changing GABA(A) receptor expression or sensitivity, is involved in premenstrual mood changes; and it also induces cognitive deficits, such as spatial-learning impairment. We have shown that the 3beta-hydroxypregnane steroid UC1011 can inhibit allopregnanolone-induced learning impairment and chloride uptake potentiation in vitro and in vivo. It would be important to find a substance that antagonizes allopregnanolone-induced adverse effects.
Collapse
Affiliation(s)
- Vita Birzniece
- Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University Hospital, Sweden
| | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
33
|
|
|
34
|
Tsoureli-Nikita E, Watson REB, Griffiths CEM. Photoageing: the darker side of the sun. Photochem Photobiol Sci 2005; 5:160-4. [PMID: 16465300 DOI: 10.1039/b507492d] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Affiliation(s)
- Evridiki Tsoureli-Nikita
- Dermatological Sciences Research Group, Faculty of Medical and Human Sciences, The University of Manchester, 1.443 Stopford Building, Oxford Road, Manchester, UK M13 9PT
| | | | | |
Collapse
|
|
35
|
Rochira V, Granata ARM, Madeo B, Zirilli L, Rossi G, Carani C. Estrogens in males: what have we learned in the last 10 years? Asian J Androl 2005; 7:3-20. [PMID: 15685347 DOI: 10.1111/j.1745-7262.2005.00018.x] [Citation(s) in RCA: 78] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
This review focuses on the role of estrogen in men, mainly in male reproduction. The continuing increase in data obtained, and recent discoveries in this area will enable a better understanding of male physiology; these, in turn, will have important clinical implications.
Collapse
Affiliation(s)
- Vincenzo Rochira
- Integrated Department of Medicine and Medical Specialties, University of Modena and Reggio Emilia, Modena 41100, Italy.
| | | | | | | | | | | |
Collapse
|
|
36
|
Abstract
Using differential display methodology, we isolated a tamoxifen-regulated cDNA. This cDNA was identical to the ps20 cDNA isolated from urogenital sinus mesenchymal cells. ps20 expression was detected in various female rat tissues, with the highest expression in lung and heart. ps20 transcripts were low during estrus and proestrus, but high during the diestrous stage of the estrous cycle coincident with estrogen-induced uterine cell proliferation. Treatment of ovary-intact or ovariectomized rats with estrogens or tamoxifen resulted in increased uterine weight and decreased ps20 expression. Uterine involution associated with ovariectomy or antiestrogen treatment led to up-regulation of ps20. Antibody against rat ps20 recognized the native rat ps20 in conditioned medium of primary rat uterine cells and stable ps20-transfected MCF-7 cells with molecular masses of approximately 24, 27, and 29 kDa. In primary rat uterine cells, ps20 secretion was enhanced by ICI 182,780, but was inhibited by estrogens and tamoxifen. Immunohistochemistry revealed that ps20 was localized to smooth muscle and luminal epithelial cells as well as the glandular population of uterine tissue. Conditioned medium derived from ps20-transfected MCF-7 cells, but not Escherichia coli recombinant ps20, exhibited mild growth suppression on PC-3 cells. The data indicate that ps20 expression is negatively regulated by estrogens and tamoxifen and suggest that ps20 may function as a mediator of local growth.
Collapse
Affiliation(s)
- Huynh Hung
- Laboratory of Molecular Endocrinology, Division of Cellular and Molecular Research, National Cancer Center of Singapore, Singapore 169610.
| |
Collapse
|
|
37
|
Rajnikant, Dinesh, Sawhney A, Mousmi, Shafiullah. X-ray crystallography of cholest-3,5-diene-7-one. CRYSTALLOGR REP+ 2005. [DOI: 10.1134/1.1927602] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
|
|
38
|
Tsukahara K, Nakagawa H, Moriwaki S, Kakuo S, Ohuchi A, Takema Y, Imokawa G. Ovariectomy is sufficient to accelerate spontaneous skin ageing and to stimulate ultraviolet irradiation-induced photoageing of murine skin. Br J Dermatol 2005; 151:984-94. [PMID: 15541076 DOI: 10.1111/j.1365-2133.2004.06203.x] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Wrinkling and sagging of the skin during photoageing is physiologically associated with diminished elasticity, which can be attributed to increased fibroblast-derived elastase activity. This degrades the dermal elastic fibres needed to maintain the three-dimensional structure of the skin. We previously reported that ovariectomy accelerates ultraviolet (UV)B-induced wrinkle formation in rat hind limb skin by altering the three-dimensional structure of elastic fibres. OBJECTIVES In this study, we used hairless mice to assess the effects of ovariectomy with or without chronic UVA or UVB radiation on sagging and wrinkling of skin, on the elasticity of skin, as well as on matrix metalloproteinase activities in the skin. METHODS Ovariectomies or sham operations were performed on 6-week-old female ICR/HR hairless mice. RESULTS Even in the ovariectomy group without UV irradiation, the skin elasticity was significantly decreased during the 3-13 weeks after ovariectomy, which was accompanied by a significant increase in elastase activity in the skin. After UVA or UVB irradiation, skin elasticity was significantly decreased to a greater extent in the ovariectomy group than in the sham operation group, and this was accompanied by a reciprocal increase in elastase activity but not in the activities of collagenases I or IV in the skin. Consistent with the decreased skin elasticity, UVA irradiation for 12 weeks elicited more marked sagging in the ovariectomy group than in the sham operation group. UVB irradiation for 12 weeks also induced more marked wrinkle formation in the ovariectomy group than in the sham operation group. CONCLUSIONS These results suggest that ovariectomy alone is sufficient to accelerate skin ageing and to increase UV sensitivity, which results in the further deterioration of the skin and photoageing, and may account for the accelerated skin ageing seen in postmenopausal women.
Collapse
Affiliation(s)
- K Tsukahara
- Department of Dermatology, Jichi Medical School, Tochigi, Japan
| | | | | | | | | | | | | |
Collapse
|
|
39
|
Affiliation(s)
- R Bellé
- Laboratoire de Physiologie de la Reproduction, Groupe Stéroïdes, Université Pierre et Marie Curie, Paris, France
| | | | | |
Collapse
|
|
40
|
Tchernitchin NN, Clavero A, Mena MA, Unda C, Villagra R, Cumsille M, Tchernitchin AN. Effect of chronic exposure to lead on estrogen action in the prepubertal rat uterus. ENVIRONMENTAL TOXICOLOGY 2003; 18:268-277. [PMID: 12900946 DOI: 10.1002/tox.10124] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/24/2023]
Abstract
Lead is a widely spread environmental pollutant known to affect both male and female reproductive systems in humans and in experimental animals. The present study investigated the effect of a chronic exposure to lead on different parameters of estrogen stimulation in the uteri of prepubertal rats. Chronic exposure to lead enhanced some parameters of estrogen stimulation, inhibited other estrogenic responses, while the remainder were unaltered. Estrogen-induced uterine eosinophilia (24 h), the proportion of uterine eosinophils in the mesometrium (6 h), and luminal epithelial hypertrophy and RNA content (24 h) appeared to be enhanced by lead exposure, compared to lead-unexposed control animals. Eosinophilia in the endometrium (6 h), the proportion of uterine eosinophils in the endometrium (6 and 24 h), edema in superficial and deep endometria (6 h), luminal epithelial hypertrophy (6 h), and mitotic response (cell proliferation) in all uterine cell types were inhibited by lead exposure, whereas circular myometrial hypertrophy was not significantly modified. The effects of lead exposure on responses to estrogen found in this study showed some differences with those previously reported for acute or subacute exposure to lead. The results revealed an interaction with the different mechanisms of estrogen action in the uterus at various levels, suggesting that some uterine cell types are more sensitive to lead than others. The relevance of the results for lead-induced infertility is discussed in this article, and possible mechanisms of action are proposed.
Collapse
Affiliation(s)
- Nina N Tchernitchin
- Laboratory of Experimental Endocrinology and Environmental Pathology, Center for Research on Environment and Biomedicine (CIMAB) and Institute of Biomedical Sciences (ICBM), University of Chile Medical School, Casilla 21104, Correo 21, Santiago, Chile
| | | | | | | | | | | | | |
Collapse
|
|
41
|
Abstract
There has been tremendous progress in the development of ligand binding assays for NRs during the past several years. A major development has been the advent of homogeneous assay formats, including those that do not require a radioligand. These high throughput, low volume assay formats will be powerful tools for the identification and characterization of novel NR ligands, including both natural ligands for orphan NRs and new drugs that mediate their therapeutic effects through this class of receptors.
Collapse
Affiliation(s)
- Stacey A Jones
- GlaxoSmithKline, Research Triangle Park, North Carolina 27709-3398, USA
| | | | | |
Collapse
|
|
42
|
Zhao H, Pang SF, Poon AMS. Variations of mt1 melatonin receptor density in the rat uterus during decidualization, the estrous cycle and in response to exogenous steroid treatment. J Pineal Res 2002; 33:140-5. [PMID: 12220327 DOI: 10.1034/j.1600-079x.2002.02898.x] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
The expression of mt1 receptor protein in the rat uterus was investigated using an anti-mt1 polyclonal antibody against the rat mt1 receptor. A melatonin receptor protein of 37 kDa was detectable by Western blotting in the rat uterine membrane preparations. Autoradiography with the melatonin ligand, 2-[125I]iodomelatonin, was used to localize melatonin receptors in the uterus of the estrous rats and to study the changes of melatonin receptors in pregnancy. Melatonin receptors were found to be localized in the estrous rat uterine antimesometrial stroma. As decidualization of the uterine stroma progressed during pregnancy, the melatonin binding sites were progressively reduced and became confined to the antimesometrial non-decidualized outer stroma. 2-[125I]Iodomelatonin binding sites were not seen in the mesometrial stromal cells during pregnancy. The role of ovarian hormones in the regulation of uterine melatonin receptors was examined by studying the binding at various phases of the estrous cycle, after ovariectomy with and without follow-on treatment of estradiol (E2), progesterone (P4) or both. 2-[125I]Iodomelatonin binding in the rat uterus fluctuated during the estrous cycle, being lowest during metestrus. Ovariectomy caused an almost 70% reduction of 2-[125I]iodomelatonin binding compared with the control. Injections of ovariectomized (OVX) rats with E2 or P4 alone or in combination for 11 days induced a partial restoration of 2-[125I]iodomelatonin binding in the OVX rats. The results show that mt1 melatonin receptors in the rat antimesometrial stroma are regulated by ovarian hormones.
Collapse
Affiliation(s)
- H Zhao
- Department of Physiology, Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | | | | |
Collapse
|
|
43
|
Nishimura T, Nakano T. Vesicles in the subacrosomal space and partial diaphragms in the subacrosomal nuclear envelope of round spermatids of a rat injected intravenously with gold labeled-testosterone-bovine serum albumin conjugate: vesicular trafficking from acrosome to nucleus. Okajimas Folia Anat Jpn 2002; 79:15-23. [PMID: 12199534 DOI: 10.2535/ofaj.79.15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Colloidal gold labeled-testosterone-bovine serum albumin conjugate (testosterone-BSA-gold) injected into the vascular system of rats is taken up by endocytosis into round spermatids. Based on observation of silver deposits indicating testosterone-BSA-gold with silver enhancement, we have suggested that testosterone-BSA-gold enters the nuclei through not only the postacrosomal nuclear envelope but also the subacrosomal nuclear envelope (SNE) via the acrosome (Nishimura and Nakano, 1997). However, it was unclear how testosterone-BSA-gold in the acrosome entered the nucleoplasm. Spermatids showing silver deposits on the subacrosomal space were observed under electron microscope without silver enhancement, to clarify the courses of translocation. In the spermatids, vesicles with the gold particles were seen in the subacrosomal space. Some of the vesicles were in contact with the SNE. A part of the outer nuclear membrane projected into the space. Furthermore, local single-bilayer nuclear membranes, which seemed to partially lack nuclear lamina, were present in the SNE. These results indicate the possibility that the vesicles mediate the transport of testosterone-BSA-gold from acrosome to nucleus, and that the vesicle membrane fuses with not only the outer nuclear membrane but also a shared bilayer in the SNE.
Collapse
Affiliation(s)
- Toshikazu Nishimura
- Department of Anatomy, Aichi Medical University School of Medicine, Yazako, Japan.
| | | |
Collapse
|
|
44
|
Rajnikant E, Gupta VK, Khan EH, Shafi S, Hashmi S, Shafiullah, Varghese B, Dinesh. Structure determination of 3β-acetoxy-cholest-5-ene-7-one—A steroid. CRYSTALLOGR REP+ 2002. [DOI: 10.1134/1.1446915] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
|
|
45
|
Rajnikant, Gupta VK, Khan EH, Shafi S, Hashmi S, Shafiullah, Varghese B, Dinesh. Crystal structure of cholest-4-ene-3,6-dione: A steroid. CRYSTALLOGR REP+ 2001. [DOI: 10.1134/1.1420827] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
|
|
46
|
Ferrero-Poüs M, Trassard M, Le Doussal V, Hacène K, Tubiana-Hulin M, Spyratos F. Comparison of enzyme immunoassay and immunohistochemical measurements of estrogen and progesterone receptors in breast cancer patients. Appl Immunohistochem Mol Morphol 2001; 9:267-75. [PMID: 11556756 DOI: 10.1097/00129039-200109000-00012] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Before replacing enzyme immunoassay of estrogen and progesterone receptors by immunohistochemistry, results of both methods were compared on 437 samples obtained from breast cancer patients (342 primary breast carcinomas, 16 local recurrences, 49 biopsies, and 30 tumor specimens obtained after neoadjuvant treatment). Immunohistochemistry (IHC) results were first assessed semiquantitatively on the basis of the estimated proportion of positive tumor cells, and then quantitatively using the "quick score." Semiquantitative IHC hormone receptors results (positive > or = 10%) correlated well with enzyme immunoassay status (positive >15 fmol/mg protein) in 358 surgical samples (342 primary tumors and 16 recurrences), with overall concordance rates of 89.9% and 82.1%, respectively. Among the 100 discordant cases, a large intraductal carcinoma component was observed in 7 of 36 cases for estrogen receptor (ER) and 15 of 64 for progesterone receptor (PR). Thirty-five discordant cases also were observed near the cut-off values. Hormone receptor levels by enzyme immunoassay correlated strongly with the quantitative IHC "quick score." Whatever the method, hormone receptor status was associated with histologic grade (SBR) and tumor size, whereas age correlated strongly with ER positivity. Similar results were obtained for biopsy specimens and posttreatment samples. This comparison improved the reliability of the IHC technique, which is currently routinely used for ER and PR determination in the authors' institution.
Collapse
Affiliation(s)
- M Ferrero-Poüs
- Laboratoire d'Oncobiologie, Center René Huguenin, Saint-Cloud, France
| | | | | | | | | | | |
Collapse
|
|
47
|
Osterlund MK, Hurd YL. Estrogen receptors in the human forebrain and the relation to neuropsychiatric disorders. Prog Neurobiol 2001; 64:251-67. [PMID: 11240308 DOI: 10.1016/s0301-0082(00)00059-9] [Citation(s) in RCA: 180] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
The steroid hormone estrogen influences brain function and neuropsychiatric disorders, but neuroanatomical information about the estrogen receptors (ERs) are rather limited. The main focus of this article is to provide an overview of the current status of the ER distribution and possible function in the human brain. The ERs are ligand activated transcription factors that belong to the steroid hormone receptors, included in the nuclear receptor superfamily. To date, there are two known ER subtypes, alpha and beta. In the human forebrain, both estrogen receptor subtypes are predominantly expressed in limbic-related areas, although they show distinct distribution patterns. The ERalpha mRNA expression appears to dominate in the hypothalamus and amygdala, indicating that the alpha-subtype might modulate neuronal cell populations involved in autonomic and reproductive neuroendocrine functions as well as emotional interpretation and processing. In contrast, the hippocampal formation, entorhinal cortex, and thalamus appear to be ERbeta dominant areas, suggesting a putative role for ERbeta in cognition, non-emotional memory and motor functions. Clinical observations of estrogenic effects together with the information available today regarding ER expression in the primate brain provide important clues as to the functional aspects of the two ER subtypes. However, further characterization of the different phenotypes of the ER expressing cells in the human brain is needed as well as the delineation of the genes which are regulated by the ERs and how this transcriptional control correlates with human behavior and mental status.
Collapse
|
|
48
|
Abstract
The speed of chemical reactions is proportional to the concentration of molecules involved. Since proteins catalyze most of the essential reactions inside a living cell, their concentration should be as high as possible. An economical way to achieve this is through the establishment of small cell compartments. We propose that within these compartments, two types of local concentration effects are at work. (1) With local concentration type I reactions, multimeric proteins bound to a specific DNA sequence have an increased local concentration for a second DNA site sufficiently close-by, or for proteins bound to such a site. (2) For type II effects, DNA can be used as a scaffold to build unique nucleoprotein complexes that would otherwise not exist free in solution. These complexes are proficient in establishing longer-range interactions with similarly unique complexes located far away on the genome. We discuss the consequences of these local concentration effects in the light of the markedly different sizes of prokaryotic and eukaryotic cells and of their genomes.
Collapse
Affiliation(s)
- P Dröge
- Institute of Genetics, University of Cologne, Germany.
| | | |
Collapse
|
|
49
|
Anderson WF, Chu KC, Chatterjee N, Brawley O, Brinton LA. Tumor variants by hormone receptor expression in white patients with node-negative breast cancer from the surveillance, epidemiology, and end results database. J Clin Oncol 2001; 19:18-27. [PMID: 11134191 DOI: 10.1200/jco.2001.19.1.18] [Citation(s) in RCA: 105] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
PURPOSE Hormone receptor expression (presence-positive or absence-negative) may reflect different stages of one disease or different breast cancer types. Determining whether hormone receptor expression represents one or more breast cancer phenotypes would have important paradigmatic and practical implications. METHODS Breast cancer records were obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. The study included 19,541 non-Hispanic white women with node-negative breast cancer. Standard tumor cell characteristics and breast cancer-specific survival were analyzed by independent estrogen receptor (ER+ and ER-), independent progesterone receptor (PR+ and PR-), and joint ERPR expression (ER+PR+, ER+PR-, ER-PR+, and ER-PR-). RESULTS Age frequency density plots by hormone receptor expression showed two overlapping breast cancer populations with early-onset and/or late-onset etiologies. Independent ER+ and PR+ phenotype were associated with smaller tumor sizes, better grade, and better cancer-specific survival than ER- and PR- breast cancer types. Joint ERPR phenotype exhibited biologic gradients for tumor size, grade, and cancer-specific survival, which ranked from good to worse for ER+PR+ to ER+PR- to ER-PR+ to ER-PR-. CONCLUSION Variations of standard tumor cell characteristics and breast cancer-specific survival by hormone receptor expression in white patients with node-negative breast cancer suggested two breast cancer phenotypes with overlapping etiologies and distinct clinical features.
Collapse
Affiliation(s)
- W F Anderson
- Division of Cancer Prevention, Office of Special Population Research, and Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7161, USA.
| | | | | | | | | |
Collapse
|
|
50
|
Pavao M, Traish AM. Estrogen receptor antibodies: specificity and utility in detection, localization and analyses of estrogen receptor alpha and beta. Steroids 2001; 66:1-16. [PMID: 11090653 DOI: 10.1016/s0039-128x(00)00143-4] [Citation(s) in RCA: 65] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
The role of estrogens in regulating cellular metabolism in many tissues is well documented. Estrogens regulate cellular activity by interacting with specific intracellular receptor proteins. Two estrogen receptor (ER) isoforms have been isolated, cloned and characterized. Estrogen receptor alpha (ERalpha) and beta (ERbeta) are ligand dependent transcriptional activators, which regulate gene expression via complex mechanisms requiring ligand binding, transformation, dimerization, and interaction with specific unique cis DNA hormone response elements (EREs) and co-activators and co-repressors. Studies of ER structure and function have been tremendously facilitated by the development of molecular and biologic probes. Cloning and functional studies of the ERalpha and ERbeta have delineated some of the structural requirements involved in receptor function. Immunochemical analyses together with biochemical and molecular approaches have contributed to our understanding of ER structure and function. Although antibodies to ER have been developed and utilized for the past two decades, there has yet to be a comprehensive review that discusses the utility and usefulness of these antibodies in receptor detection and analysis. In this review, we summarize a plethora of information concerning the development and characterization of site-directed monoclonal and polyclonal antibodies to the ERalpha and ERbeta. We provide critical discussion on the characteristics and utility of ER antibodies in analyses, characterization and localization of ER isoforms in various tissues. We also provide a comparison of the potential utility of the available antibodies in various immunochemical assays. An epitope map detailing the specific sites of antibody-receptor interactions is constructed based on the available information. The advent of antibodies with high specificity and titer had facilitated detection of ER isoforms in normal and neoplastic tissues. The advent of new antibodies remains a powerful tool for assessment of ER expression and post-translational modification and receptor function in many experimental systems.
Collapse
Affiliation(s)
- M Pavao
- Department of Biochemistry, Center for Advanced Biomedical Research, Boston University School of Medicine, 700 Albany Street, W-607, Boston, MA 02118, USA
| | | |
Collapse
|