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Nalbantoğlu Ö, Hazan F, Acar S, Gürsoy S, Özkan B. Screening of non-syndromic early-onset child and adolescent obese patients in terms of LEP, LEPR, MC4R and POMC gene variants by next-generation sequencing. J Pediatr Endocrinol Metab 2022; 35:1041-1050. [PMID: 35801948 DOI: 10.1515/jpem-2022-0027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Accepted: 06/16/2022] [Indexed: 11/15/2022]
Abstract
OBJECTIVES Non-syndromic monogenic obesity is a rare cause of early-onset severe obesity in the childhood period. The aim of this study was to screen four obesity related genes (LEP, LEPR, MC4R and POMC) in children and adolescents who had severe, non-syndromic early onset obesity. METHODS Next-generation sequencing of all exons in LEP, LEPR, MC4R and POMC was performed in 154 children and adolescents with early onset severe obesity obesity. RESULTS Fifteen different variants in nineteen patients were identified with a variant detection rate of 12.3%. While six different heterozygous variants were observed in MC4R gene (10/154 patients; 6.5%), five different variants in POMC gene (four of them were heterozygous and one of them was homozygous) (6/154 patients; 3.9%) and four different homozygous variants in LEPR gene (3/154 patients; 1.9%) were described. However, no variants were detected in the LEP gene. The most common pathogenic variant was c.496G>A in MC4R gene, which was detected in four unrelated patients. Six novel variants (6/15 variants; 40%) were described in seven patients. Four of them including c.233C>A and c.752T>C in MC4R gene and c.761dup and c.1221dup in LEPR gene were evaluated as pathogenic or likely pathogenic. CONCLUSIONS In conclusion, MC4R variants are the most common genetic cause of monogenic early-onset obesity, consistent with the literature. The c.496G>A variant in MC4R gene is highly prevalent in early-onset obese patients.
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Affiliation(s)
- Özlem Nalbantoğlu
- Clinic of Pediatric Endocrinology, University of Health Sciences Turkey, Dr. BehçetUz Child Disease and Pediatric Surgery Training and Research Hospital, İzmir, Turkey
| | - Filiz Hazan
- Clinic of Medical Genetics, University of Health Sciences Turkey, Dr. BehçetUz Child Disease and Pediatric Surgery Training and Research Hospital, İzmir, Turkey
| | - Sezer Acar
- Clinic of Pediatric Endocrinology, University of Health Sciences Turkey, Dr. BehçetUz Child Disease and Pediatric Surgery Training and Research Hospital, İzmir, Turkey
| | - Semra Gürsoy
- Clinic of Pediatric Genetics, University of Health Sciences Turkey, Dr. BehçetUz Child Disease and Pediatric Surgery Training and Research Hospital, İzmir, Turkey
| | - Behzat Özkan
- Clinic of Pediatric Endocrinology, University of Health Sciences Turkey, Dr. BehçetUz Child Disease and Pediatric Surgery Training and Research Hospital, İzmir, Turkey
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Calcaterra V, Verduci E, Magenes VC, Pascuzzi MC, Rossi V, Sangiorgio A, Bosetti A, Zuccotti G, Mameli C. The Role of Pediatric Nutrition as a Modifiable Risk Factor for Precocious Puberty. Life (Basel) 2021; 11:1353. [PMID: 34947884 PMCID: PMC8706413 DOI: 10.3390/life11121353] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Revised: 12/04/2021] [Accepted: 12/06/2021] [Indexed: 12/19/2022] Open
Abstract
Puberty is a critical phase of growth and development characterized by a complex process regulated by the neuroendocrine system. Precocious puberty (PP) is defined as the appearance of physical and hormonal signs of pubertal development at an earlier age than is considered normal. The timing of puberty has important public health, clinical, and social implications. In fact, it is crucial in psychological and physical development and can impact future health. Nutritional status is considered as one of the most important factors modulating pubertal development. This narrative review presents an overview on the role of nutritional factors as determinants of the timing of sexual maturation, focusing on early-life and childhood nutrition. As reported, breast milk seems to have an important protective role against early puberty onset, mainly due to its positive influence on infant growth rate and childhood overweight prevention. The energy imbalance, macro/micronutrient food content, and dietary patterns may modulate the premature activation of the hypothalamic-pituitary-gonadal axis, inducing precocious activation of puberty. An increase in knowledge on the mechanism whereby nutrients may influence puberty will be useful in providing adequate nutritional recommendations to prevent PP and related complications.
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Affiliation(s)
- Valeria Calcaterra
- Pediatric Department, “Vittore Buzzi” Children’s Hospital, 20154 Milan, Italy; (V.C.); (V.C.M.); (M.C.P.); (V.R.); (A.S.); (A.B.); (G.Z.); (C.M.)
- Pediatric and Adolescent Unit, Department of Internal Medicine, University of Pavia, 27100 Pavia, Italy
| | - Elvira Verduci
- Pediatric Department, “Vittore Buzzi” Children’s Hospital, 20154 Milan, Italy; (V.C.); (V.C.M.); (M.C.P.); (V.R.); (A.S.); (A.B.); (G.Z.); (C.M.)
- Department of Health Sciences, University of Milan, 20142 Milan, Italy
| | - Vittoria Carlotta Magenes
- Pediatric Department, “Vittore Buzzi” Children’s Hospital, 20154 Milan, Italy; (V.C.); (V.C.M.); (M.C.P.); (V.R.); (A.S.); (A.B.); (G.Z.); (C.M.)
| | - Martina Chiara Pascuzzi
- Pediatric Department, “Vittore Buzzi” Children’s Hospital, 20154 Milan, Italy; (V.C.); (V.C.M.); (M.C.P.); (V.R.); (A.S.); (A.B.); (G.Z.); (C.M.)
| | - Virginia Rossi
- Pediatric Department, “Vittore Buzzi” Children’s Hospital, 20154 Milan, Italy; (V.C.); (V.C.M.); (M.C.P.); (V.R.); (A.S.); (A.B.); (G.Z.); (C.M.)
| | - Arianna Sangiorgio
- Pediatric Department, “Vittore Buzzi” Children’s Hospital, 20154 Milan, Italy; (V.C.); (V.C.M.); (M.C.P.); (V.R.); (A.S.); (A.B.); (G.Z.); (C.M.)
| | - Alessandra Bosetti
- Pediatric Department, “Vittore Buzzi” Children’s Hospital, 20154 Milan, Italy; (V.C.); (V.C.M.); (M.C.P.); (V.R.); (A.S.); (A.B.); (G.Z.); (C.M.)
| | - Gianvincenzo Zuccotti
- Pediatric Department, “Vittore Buzzi” Children’s Hospital, 20154 Milan, Italy; (V.C.); (V.C.M.); (M.C.P.); (V.R.); (A.S.); (A.B.); (G.Z.); (C.M.)
- Department of Biomedical and Clinical Science “L. Sacco”, University of Milan, 20157 Milan, Italy
| | - Chiara Mameli
- Pediatric Department, “Vittore Buzzi” Children’s Hospital, 20154 Milan, Italy; (V.C.); (V.C.M.); (M.C.P.); (V.R.); (A.S.); (A.B.); (G.Z.); (C.M.)
- Department of Biomedical and Clinical Science “L. Sacco”, University of Milan, 20157 Milan, Italy
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Calcaterra V, Cena H, Regalbuto C, Vinci F, Porri D, Verduci E, Mameli C, Zuccotti GV. The Role of Fetal, Infant, and Childhood Nutrition in the Timing of Sexual Maturation. Nutrients 2021; 13:419. [PMID: 33525559 PMCID: PMC7911282 DOI: 10.3390/nu13020419] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 01/21/2021] [Accepted: 01/23/2021] [Indexed: 12/28/2022] Open
Abstract
Puberty is a crucial developmental stage in the life span, necessary to achieve reproductive and somatic maturity. Timing of puberty is modulated by and responds to central neurotransmitters, hormones, and environmental factors leading to hypothalamic-pituitary-gonadal axis maturation. The connection between hormones and nutrition during critical periods of growth, like fetal life or infancy, is fundamental for metabolic adaptation response and pubertal development control and prediction. Since birth weight is an important indicator of growth estimation during fetal life, restricted prenatal growth, such as intrauterine growth restriction (IUGR) and small for gestational age (SGA), may impact endocrine system, affecting pubertal development. Successively, lactation along with early life optimal nutrition during infancy and childhood may be important in order to set up timing of sexual maturation and provide successful reproduction at a later time. Sexual maturation and healthy growth are also influenced by nutrition requirements and diet composition. Early nutritional surveillance and monitoring of pubertal development is recommended in all children, particularly in those at risk, such as the ones born SGA and/or IUGR, as well as in the case of sudden weight gain during infancy. Adequate macro and micronutrient intake is essential for healthy growth and sexual maturity.
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Affiliation(s)
- Valeria Calcaterra
- Pediatric and Adolescent Unit, Department of Internal Medicine, University of Pavia, 27100 Pavia, Italy
- Pediatric Unit, “V. Buzzi” Children’s Hospital, 20154 Milan, Italy; (E.V.); (C.M.); (G.V.Z.)
| | - Hellas Cena
- Laboratory of Dietetics and Clinical Nutrition, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy; (H.C.); (D.P.)
- Clinical Nutrition and Dietetics Service, Unit of Internal Medicine and Endocrinology, ICS Maugeri IRCCS, 27100 Pavia, Italy
| | - Corrado Regalbuto
- Pediatric Unit, Fond, IRCCS Policlinico S. Matteo and University of Pavia, 27100 Pavia, Italy; (C.R.); (F.V.)
| | - Federica Vinci
- Pediatric Unit, Fond, IRCCS Policlinico S. Matteo and University of Pavia, 27100 Pavia, Italy; (C.R.); (F.V.)
| | - Debora Porri
- Laboratory of Dietetics and Clinical Nutrition, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy; (H.C.); (D.P.)
| | - Elvira Verduci
- Pediatric Unit, “V. Buzzi” Children’s Hospital, 20154 Milan, Italy; (E.V.); (C.M.); (G.V.Z.)
- Department of Health Sciences, University of Milano, 20142 Milano, Italy
| | - Chiara Mameli
- Pediatric Unit, “V. Buzzi” Children’s Hospital, 20154 Milan, Italy; (E.V.); (C.M.); (G.V.Z.)
- “L. Sacco” Department of Biomedical and Clinical Science, University of Milan, 20157 Milan, Italy
| | - Gian Vincenzo Zuccotti
- Pediatric Unit, “V. Buzzi” Children’s Hospital, 20154 Milan, Italy; (E.V.); (C.M.); (G.V.Z.)
- “L. Sacco” Department of Biomedical and Clinical Science, University of Milan, 20157 Milan, Italy
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Abbasihormozi S, Shahverdi A, Kouhkan A, Cheraghi J, Akhlaghi AA, Kheimeh A. Relationship of leptin administration with production of reactive oxygen species, sperm DNA fragmentation, sperm parameters and hormone profile in the adult rat. Arch Gynecol Obstet 2012; 287:1241-9. [PMID: 23269353 DOI: 10.1007/s00404-012-2675-x] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2012] [Accepted: 12/03/2012] [Indexed: 11/30/2022]
Abstract
PURPOSE Leptin, an adipose tissue-derived hormone, plays an important role in energy homeostasis and metabolism, and in the neuroendocrine and reproductive systems. The function of leptin in male reproduction is unclear; however, it is known to affect sex hormones, sperm motility and its parameters. Leptin induces mitochondrial superoxide production in aortic endothelia and may increase oxidative stress and abnormal sperm production in leptin-treated rats. This study aims to evaluate whether exogenous leptin affects sperm parameters, hormone profiles, and the production of reactive oxygen species (ROS) in adult rats. METHODS A total of 65 Sprague-Dawley rats were divided into three treated groups and a control group. Treated rats received daily intraperitoneal injections of 5, 10 and 30 μg/kg of leptin administered for a duration of 7, 15, and 42 days. Control rats were given 0.1 mL of 0.9 % normal saline for the same period. One day after final drug administration, we evaluated serum specimens for follicle-stimulating hormone (FSH), leutinizing hormone (LH), free testosterone (FT), and total testosterone (TT) levels. Samples from the rat epididymis were also evaluated for sperm parameters and motility characteristics by a Computer-Aided Semen Analysis (CASA) system. Samples were treated with 2',7'-dichlorofluorescein-diacetate (DCFH-DA) and analyzed using flow cytometry and TUNEL to determine the impact of leptin administration on sperm DNA fragmentation. RESULTS According to CASA, significant differences in all sperm parameters in leptin-treated rats and their age-matched controls were detected, except for TM, ALH and BCF. Serum FSH and LH levels were significantly higher in rats that received 10 and 30 μg/kg of leptin compared to those treated with 5 μg/kg of leptin in the same group and control rats (P < 0.05). ROS and sperm DNA fragmentation was significantly higher in rats injected with 10 and 30 μg/kg of leptin for 7 and 15 days compared with rats treated with 5 μg/kg of leptin and the control group (P < 0.05) for the same time period. However, at day 42 of treatment, ROS and sperm DNA fragmentation levels significantly decreased in all groups (P < 0.05). CONCLUSION According to these results, leptin can possibly affect male infertility by ROS induction or hormone profile modulation.
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Affiliation(s)
- Shima Abbasihormozi
- Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, 16635-148, Tehran, Iran
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Rauchfuss M, Fischer T, Bogner G, Maier B. Influence of so far neglected psychosomatic factors, BMI and smoking on pregnancy-induced hypertension (PIH). Pregnancy Hypertens 2012; 2:93-100. [DOI: 10.1016/j.preghy.2011.11.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2011] [Accepted: 11/28/2011] [Indexed: 10/14/2022]
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Yang H, Sukocheva OA, Hussey DJ, Watson DI. Estrogen, male dominance and esophageal adenocarcinoma: is there a link? World J Gastroenterol 2012; 18:393-400. [PMID: 22346245 PMCID: PMC3270506 DOI: 10.3748/wjg.v18.i5.393] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2011] [Revised: 08/11/2011] [Accepted: 08/15/2011] [Indexed: 02/06/2023] Open
Abstract
Esophageal adenocarcinoma is a cancer with poor prognosis, and its incidence has risen sharply over recent decades. Obesity is a major risk factor for developing this cancer and there is a clear male gender bias in the incidence that cannot be fully explained by known risk factors. It is possible that a difference in the expression of estrogen, or its signaling axes, may contribute to this gender bias. We undertook a comprehensive literature search and analyzed the available data regarding estrogen and estrogen receptor expression, and the possible sex-specific links with esophageal adenocarcinoma development. Potentially relevant associations between visceral vs subcutaneous fat deposition and estrogen expression, and the effect of crosstalk between estrogen and leptin signaling were identified. We also found limited studies suggesting a role for estrogen receptor β expression in esophageal adenocarcinoma development. The current literature supports speculation on an etiological role for estrogen in the male gender bias in esophageal adenocarcinoma, but further studies are required.
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Xi H, Zhang L, Guo Z, Zhao L. Serum Leptin Concentration and Its Effect on Puberty in Naqu Tibetan Adolescents. J Physiol Anthropol 2011; 30:111-7. [DOI: 10.2114/jpa2.30.111] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
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Martos-Moreno GA, Chowen JA, Argente J. Metabolic signals in human puberty: effects of over and undernutrition. Mol Cell Endocrinol 2010; 324:70-81. [PMID: 20026379 DOI: 10.1016/j.mce.2009.12.017] [Citation(s) in RCA: 71] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2009] [Revised: 12/08/2009] [Accepted: 12/11/2009] [Indexed: 01/19/2023]
Abstract
Puberty in mammals is associated with important physical and psychological changes due to the increase in sex steroids and growth hormone (GH). Indeed, an increase in growth velocity and the attainment of sexual maturity for future reproductive function are the hallmark changes during this stage of life. Both growth and reproduction consume high levels of energy, requiring suitable energy stores to face these physiological functions. During the last two decades our knowledge concerning how peptides produced in the digestive tract (in charge of energy intake) and in adipose tissue (in charge of energy storage) provide information regarding metabolic status to the central nervous system (CNS) has increased dramatically. Moreover, these peptides have been shown to play an important role in modulating the gonadotropic axis with their absence or an imbalance in their secretion being able to disturb pubertal onset or progression. In this article we will review the current knowledge concerning the role played by leptin, the key adipokine in energy homeostasis, and ghrelin, the only orexigenic and growth-promoting peptide produced by the digestive tract, on sexual development. The normal evolutionary pattern of these peripherally produced metabolic signals throughout human puberty will be summarized. The effect of two opposite situations of chronic malnutrition, obesity and anorexia, on these signals and how they influence the course of puberty will also be discussed. Finally, we will briefly mention other peptides derived from the digestive tract (such as PYY) that may be involved in the regulatory link between energy homeostasis and sexual development.
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Affiliation(s)
- G A Martos-Moreno
- Hospital Infantil Universitario Niño Jesús, Department of Endocrinology, Universidad Autónoma de Madrid, Madrid, Spain
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Cammisotto PG, Levy E, Bukowiecki LJ, Bendayan M. Cross-talk between adipose and gastric leptins for the control of food intake and energy metabolism. ACTA ACUST UNITED AC 2010; 45:143-200. [PMID: 20621336 DOI: 10.1016/j.proghi.2010.06.001] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/06/2010] [Indexed: 12/25/2022]
Abstract
The understanding of the regulation of food intake has become increasingly complex. More than 20 hormones, both orexigenic and anorexigenic, have been identified. After crossing the blood-brain barrier, they reach their main site of action located in several hypothalamic areas and interact to balance satiety and hunger. One of the most significant advances in this matter has been the discovery of leptin. This hormone plays fundamental roles in the control of appetite and in regulating energy expenditure. In accordance with the lipostatic theory stated by Kennedy in 1953, leptin was originally discovered in white adipose tissue. Its expression by other tissues was later established. Among them, the gastric mucosa has been shown to secrete large amounts of leptin. Both the adipose and the gastric tissues share similar characteristics in the synthesis and storage of leptin in granules, in the formation of a complex with the soluble receptor and a secretion modulated by hormones and energy substrates. However while adipose tissue secretes leptin in a slow constitutive endocrine way, the gastric mucosa releases leptin in a rapid regulated exocrine fashion into the gastric juice. Exocrine-secreted leptin survives the extreme hydrolytic conditions of the gastric juice and reach the duodenal lumen in an intact active form. Scrutiny into transport mechanisms revealed that a significant amount of the exocrine leptin crosses the intestinal wall by active transcytosis. Leptin receptors, expressed on the luminal and basal membrane of intestinal epithelial cells, are involved in the control of nutrient absorption by enterocytes, mucus secretion by goblet cells and motility, among other processes, and this control is indeed different depending upon luminal or basal stimulus. Gastric leptin after transcytosis reaches the central nervous system, to control food intake. Studies using the Caco-2, the human intestinal cell line, in vitro allowed analysis of the mechanisms of leptin actions on the intestinal mucosa, identification of the mechanisms of leptin transcytosis and understanding the modulation of leptin receptors by nutrients and hormones. Exocrine-secreted gastric leptin thus participates in a physiological axis independent in terms of time and regulation from that of adipose tissue to rapidly control food intake and nutrient absorption. Adipocytes and gastric epithelial cells are two cell types the metabolism of which is closely linked to food intake and energy storage. The coordinated secretion of adipose and gastric leptins ensures proper management of food processing and energy storage.
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Affiliation(s)
- Philippe G Cammisotto
- Department of Pathology and Cell Biology, University of Montreal, 2900 Boulevard Edouard-Montpetit, Montreal, QC, Canada.
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Hatami-Baroogh L, Razavi S, Zarkesh-Esfahani H, Tavalaee M, Tanhaei S, Ghaedi K, Deemeh MR, Rabiee F, Nasr-Esfahani MH. Evaluation of the leptin receptor in human spermatozoa. Reprod Biol Endocrinol 2010; 8:17. [PMID: 20178606 PMCID: PMC2841190 DOI: 10.1186/1477-7827-8-17] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2009] [Accepted: 02/23/2010] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Leptin, a 167 amino acid peptide hormone, profoundly effects reproduction exerting its biological effects via interaction with the leptin receptor (ObR) which is widely expressed on peripheral tissues. In this study, we have attempted to assess leptin receptor expression in the spermatozoa of fertile males and those diagnosed with male factor infertility; both at the mRNA or protein levels. METHODS Semen samples were collected from fertile males and individuals with male factor infertility. In order to evaluate leptin receptor expression several techniques were utilized, including: reverse transcriptase-polymerase chain reaction (RT-PCR), immunostaining, flow cytometry, and western blotting. Mononuclear cells isolated from volunteers' peripheral blood were used as positive controls for leptin receptor expression. RESULTS leptin receptor was noted on mononuclear cells but we were unable to detect this receptor on spermatozoa at the protein level. Leptin receptor expression was detected on peripheral blood mononuclear cells (PBMCs) as positive controls; however it was not detectable on the spermatozoa of both groups by immunofluorescence microscopy or flow cytometry. Furthermore, positive expression of the ObR long isoform as assessed by RT-PCR was observed in the sperm of only four cases, whereas expression of beta-Actin, a house keeping gene, and HspA2, a testis specific gene, was present in all cases. CONCLUSION The long isoform of leptin receptor may not be present on human sperm. Species difference may be accounted for diverse reproductive physiology which depends on metabolic requirement. Leptin receptor expression at the mRNA level in some individuals may be related to contamination by other cells in semen.
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Affiliation(s)
- Leila Hatami-Baroogh
- Department of Biology, Science and Culture University, Tehran, Iran
- Department of Reproduction and Development, Royan Institute for Animal Biotechnology, ACER, Isfahan, Iran
| | - Shahnaz Razavi
- Department of Anatomy, Isfahan Medical University, Isfahan, Iran
| | | | - Marziyeh Tavalaee
- Department of Reproduction and Development, Royan Institute for Animal Biotechnology, ACER, Isfahan, Iran
| | - Somayeh Tanhaei
- Department of Cell and Molecular Biology, Royan Institute for Animal Biotechnology, ACECR, Isfahan, Iran
| | - Kamran Ghaedi
- Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran
- Department of Cell and Molecular Biology, Royan Institute for Animal Biotechnology, ACECR, Isfahan, Iran
| | | | - Farzaneh Rabiee
- Department of Cell and Molecular Biology, Royan Institute for Animal Biotechnology, ACECR, Isfahan, Iran
| | - Mohammad Hossein Nasr-Esfahani
- Department of Reproduction and Development, Royan Institute for Animal Biotechnology, ACER, Isfahan, Iran
- Department of Cell and Molecular Biology, Royan Institute for Animal Biotechnology, ACECR, Isfahan, Iran
- Isfahan Fertility and Infertility Center, Isfahan, Iran
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Shi H, Seeley RJ, Clegg DJ. Sexual differences in the control of energy homeostasis. Front Neuroendocrinol 2009; 30:396-404. [PMID: 19341761 PMCID: PMC4517605 DOI: 10.1016/j.yfrne.2009.03.004] [Citation(s) in RCA: 181] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2008] [Revised: 03/09/2009] [Accepted: 03/17/2009] [Indexed: 12/20/2022]
Abstract
The prevalence of obesity has reached epidemic proportion with enormous costs in both human lives and healthcare dollars spent. Obesity-related metabolic disorders are much lower in premenopausal women than men; however, there is a dramatic increase following menopause in women. The health risks associated with obesity vary depending on the location of adipose tissue. Adipose tissue distributed in the abdominal visceral carry a much greater risk for metabolic disorders than does adipose tissue distributed subcutaneously. There are distinct sex-dependent differences in the regional fat distribution, women carry more fat subcutaneously whereas men carry more fat viscerally. Males and females differ with respect to their regulation of energy homeostasis. Peripheral adiposity hormones such as leptin and insulin as well as sex hormones directly influence energy balance. Sexual dimorphisms in energy balance, body fat distribution, and the role sex hormones have in mediating these differences are the focus of this review.
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Affiliation(s)
- Haifei Shi
- Obesity Research Center, University of Cincinnati, Cincinnati, OH, USA
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Shi H, Clegg DJ. Sex differences in the regulation of body weight. Physiol Behav 2009; 97:199-204. [PMID: 19250944 DOI: 10.1016/j.physbeh.2009.02.017] [Citation(s) in RCA: 196] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2009] [Revised: 02/12/2009] [Accepted: 02/20/2009] [Indexed: 10/21/2022]
Abstract
Obesity and its associated health disorders and costs are increasing. Males and females differ in terms of how and where body fat is stored, the hormones they secrete in proportion to their fat, and the way their brains respond to signals that regulate body fat. Fat accumulation in the intra-abdominal adipose depot is associated with the risk for developing cardiovascular problems, type-2 diabetes mellitus, certain cancers and other disorders. Men and postmenopausal women accumulate more fat in the intra-abdominal depot than do pre-menopausal women, and therefore have a greater risk of developing metabolic complications associated with obesity. The goal of this review is to explore what we know about sexual dimorphisms in adipose tissue accrual and deposition. Elucidating the mechanisms by which sex hormones may modulate the way in which fat is accumulated and stored is a critical area of research due to the prevalence of obesity and the metabolic syndrome, and the rapid increase in propensity for these diseases following menopause.
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Affiliation(s)
- H Shi
- Department of Psychiatry, College of Medicine, University of Cincinnati, Cincinnati, OH 45237, USA
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Weight change and appetite disturbance as symptoms of adolescent depression: toward an integrative biopsychosocial model. Clin Psychol Rev 2009; 29:260-73. [PMID: 19250729 DOI: 10.1016/j.cpr.2009.01.007] [Citation(s) in RCA: 62] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2008] [Revised: 01/22/2009] [Accepted: 01/29/2009] [Indexed: 11/22/2022]
Abstract
The Diagnostic and Statistical Manual of Mental Disorders [American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (4th ed.). Washington, DC: Author.] lists weight change and appetite disturbance as a single compound symptom of depression at all ages. Nonetheless, assessment of these symptoms is complicated during adolescence by normative increases in body weight and appetitive drive as well as heightened rates of body dissatisfaction, dieting, and eating disorders. This review outlines biological and psychological mechanisms that may change the relation of weight change and appetite disturbance to depression during adolescence. We propose a developmental model of the relation of these symptoms to the disorder and use the model as a framework to summarize findings, limitations, and future directions of research. Although the literature suggests that weight change and appetite disturbance are related to adolescent depression, preliminary evidence suggests that interpretation of weight and appetite symptoms may depend on developmental level.
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Huang XD, Fan Y, Zhang H, Wang P, Yuan JP, Li MJ, Zhan XY. Serum leptin and soluble leptin receptor in non-alcoholic fatty liver disease. World J Gastroenterol 2008; 14:2888-93. [PMID: 18473416 PMCID: PMC2710733 DOI: 10.3748/wjg.14.2888] [Citation(s) in RCA: 63] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the role of leptin system in non-alcoholic fatty liver disease (NAFLD) development by delineating the changes in serum levels of leptin and soluble leptin receptor (sOB-R).
METHODS: Blood samples were collected from 30 consecutive patients with liver-biopsy-proven NAFLD and 30 patients with cholecystolithiasis (stationary phase) as controls. Serum leptin levels were determined by radioimmunoassay and concentration of sOB-R was measured by ELISA. Body mass index (BMI) was calculated for all subjects, and serum insulin, C-peptide, and lipoprotein levels were also detected.
RESULTS: Mean serum leptin level and BMI in the NAFLD group were significantly higher than in the controls (both P < 0.001), but mean sOB-R level was lower in the NAFLD group when compared to the controls. Both men and women in the NAFLD group had higher mean serum leptin levels and lower sOB-R levels than did the men and women in the control group (all P < 0.001). There was a significant negative correlation between serum leptin and sOB-R levels (r = -0.725, P < 0.001). Multivariate analysis showed that the percentage of hepatocyte steatosis, sex, BMI, and homeostasis model assessment of insulin resistance (HOMA IR) were independently related to serum leptin levels.
CONCLUSION: Elevated serum leptin seems to be a feature of steatosis, and serum leptin seems to increase as hepatocyte steatosis develops. An enhanced release of leptin is accompanied by an decrease in sOB-R concentration, which suggests higher resistance of peripheral tissues towards the action of leptin.
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Zieba DA, Amstalden M, Williams GL. Regulatory roles of leptin in reproduction and metabolism: a comparative review. Domest Anim Endocrinol 2005; 29:166-85. [PMID: 15927772 DOI: 10.1016/j.domaniend.2005.02.019] [Citation(s) in RCA: 133] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2005] [Revised: 02/10/2005] [Accepted: 02/19/2005] [Indexed: 11/30/2022]
Abstract
Leptin plays an important role in signaling nutritional status to the central reproductive axis of mammals and appears to be at least a permissive factor in the initiation of puberty. The expression and secretion of leptin are correlated with body fat mass and are acutely affected by changes in feed intake. Moreover, circulating leptin increases during pubertal development in rodents, human females and heifers. Effects of leptin are mediated mainly via receptor activation of the JAK-STAT pathway; however, activation of alternative pathways, such as MAP kinase, has also been reported. Although the leptin receptor (LR) has not been found on GnRH neurons, leptin stimulates the release of GnRH from rat and porcine hypothalamic explants. Moreover, leptin increases the release of LH in rats and from adenohypophyseal explants and/or cells from full-fed rats and pigs. In contrast, stimulation of the hypothalamic-gonadotropic axis by leptin in cattle and sheep is observed predominantly in animals and tissues pre-exposed to profound negative energy balance. For example, leptin prevents fasting-mediated reductions in the frequency of LH pulses in peripubertal heifers, augments the magnitude of LH and GnRH pulses in fasted cows, and enhances basal secretion of LH in vivo and from adenohypophyseal explants of fasted cows. However, leptin is incapable of accelerating the frequency of LH pulses in prepubertal heifers, regardless of nutrient status, and has no effect on the secretion of GnRH and LH in full-fed cattle or hypothalamic/hypophyseal explants derived thereof. Similar to results obtained with LH, basal secretion of GH from anterior pituitary explants of fasted, but not normal-fed cows, was potentiated acutely by low, but not high, doses of leptin. Mechanisms through which undernutrition hypersensitize the hypothalamic-gonadotropic axis to leptin may involve up-regulation of the LR. However, an increase in LR mRNA expression is not a requisite feature of heightened adenohypophyseal responses in fasted cattle. To date, leptin has not been successful for inducing puberty in ruminants. Future therapeutic uses for recombinant leptin that exploit states of nutritional hypersensitization, and identification of genetic markers for genotypic variation in leptin resistance, are currently under investigation.
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Affiliation(s)
- D A Zieba
- Animal Reproduction Laboratory, Texas A&M University Agricultural Research Station, 3507 Hwy 59E, Beeville, TX 78102, USA
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16
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Bhat GK, Plant TM, Mann DR. Relationship between serum concentrations of leptin, soluble leptin receptor, testosterone and IGF-I, and growth during the first year of postnatal life in the male rhesus monkey, Macaca mulatta. Eur J Endocrinol 2005; 153:153-8. [PMID: 15994757 DOI: 10.1530/eje.1.01939] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
OBJECTIVES Subnormal leptin levels in low birth weight infants may allow for catch-up growth during infancy. Scant data are available that relate growth with circulating leptin during normal infancy in primates. The current study objective was to examine the association between serum leptin, its soluble receptor (sOB-R), testosterone and IGF-I concentrations, and body weight during infancy in male rhesus monkeys. DESIGN Hormone levels were assessed longitudinally in animals (n = 7) from birth until 1 year of age. RESULTS Body weight increased during the first 6 months of life and was strongly correlated with rising IGF-I levels and, as IGF-I plateaued and then declined during the second half of the year, body weight gain decelerated. In contrast, leptin levels declined gradually with age during the first year of life in conjunction with increasing body weight. There was no association between body weight gain and serum leptin levels or between serum testosterone and leptin values. Since sOB-R levels also declined with leptin values, it does not appear that levels of bioavailable leptin changed during infancy. CONCLUSIONS The data do not support the contention that leptin regulates growth during infancy, but the close association between IGF-I levels and body weight suggested that this hormone may regulate growth in infant male monkeys. The failure to observe an association between serum testosterone and leptin concentrations suggested that leptin is not involved in the activation of the hypothalamic-pituitary -testicular axis during this developmental period.
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Affiliation(s)
- Ganapathy K Bhat
- Department of Physiology and the Cooperative Reproductive Science Research Center, Morehouse School of Medicine, Atlanta, Georgia 30310, USA
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Zarkesh-Esfahani H, Pockley AG, Wu Z, Hellewell PG, Weetman AP, Ross RJM. Leptin indirectly activates human neutrophils via induction of TNF-alpha. THE JOURNAL OF IMMUNOLOGY 2004; 172:1809-14. [PMID: 14734764 DOI: 10.4049/jimmunol.172.3.1809] [Citation(s) in RCA: 173] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Leptin, the satiety hormone, appears to act as a link between nutritional status and immune function. It has been shown to elicit a number of immunoregulatory effects, including the promotion of T cell proliferative responses, and the induction of proinflammatory cytokines. Leptin deficiency is associated with an increased susceptibility to infection. As polymorphonuclear neutrophils (PMN) play a major role in innate immunity and host defense against infection, this study evaluated the influence of leptin on PMN activation. The presence of leptin receptor in human PMN was determined both at mRNA and protein levels, and the effect of leptin on PMN activation, as assessed by CD11b expression, was evaluated using flow cytometry. In contrast to monocytes, which express both the short and long forms of the leptin receptor (Ob-Ra and Ob-Rb, respectively), PMN expressed only Ob-Ra. Leptin up-regulated the expression of CD11b, an early marker of PMN activation, on PMN in whole blood, yet it had no effect on purified PMN, even those treated by submaximal doses of TNF-alpha or PMA. The kinetics of leptin-induced activation in whole blood were consistent with an indirect effect mediated by monocytes, and 71% of the leptin-stimulatory effect on PMN was blocked by a TNF-alpha inhibitor. Leptin-mediated induction of CD11b expression was observed when purified PMN were coincubated with purified monocytes. In conclusion, although leptin activates PMN, it does so indirectly via TNF-alpha release from monocytes. These findings provide an additional link among the obesity-derived hormone leptin, innate immune function, and infectious disease.
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Affiliation(s)
- Hamid Zarkesh-Esfahani
- Division of Clinical Sciences (North), University of Sheffield, Sheffield, United Kingdom
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18
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Geisthövel F, Jochmann N, Widjaja A, Horn R, Brabant G. Serum pattern of circulating free leptin, bound leptin, and soluble leptin receptor in the physiological menstrual cycle. Fertil Steril 2004; 81:398-402. [PMID: 14967380 DOI: 10.1016/j.fertnstert.2003.06.020] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2003] [Revised: 06/19/2003] [Accepted: 06/19/2003] [Indexed: 11/25/2022]
Abstract
OBJECTIVE To investigate the serum pattern of free leptin, bound leptin, and soluble leptin receptor throughout the physiological menstrual cycle. DESIGN Prospective observational study. SETTING Tertiary care center for gynecological endocrinology and reproductive medicine and a university research laboratory. PATIENT(S) Thirty regularly cycling volunteers (age, 29 +/- 4.2 years). INTERVENTION(S) Blood sampling was performed at different phases (early and mid follicular phase, preovulatory phase, and early and late luteal phase) of three consecutive menstrual cycles; each phase of the menstrual cycle was investigated twice. MAIN OUTCOME MEASURE(S) Free leptin, bound leptin, soluble leptin receptor, LH, E(2), P, vaginal ultrasound. RESULT(S) A peak of serum free leptin levels was found in the late luteal phase followed by a significant drop in the early follicular phase and again by a continuous increase up to the next luteal peak. There were no significant alterations in serum bound leptin and soluble leptin receptor levels. CONCLUSION(S) The present study shows that there are significant circacyclic fluctuations of free leptin levels with the highest concentrations in the late luteal phase and the lowest levels in the early follicular phase, which suggests that circulating free leptin is up-regulated by the C(21)-steroid (P). Circulating bound leptin and soluble leptin receptor are not altered by the cyclic hormone status. The significant rise of the leptin bioequivalent, free leptin, in the late luteal phase might be of importance for the luteal-follicular and the luteal-preimplantatory functional shift.
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Affiliation(s)
- Franz Geisthövel
- Center for Gynecological Endocrinology and Reproductive Medicine, Freiburg im Breisgau, Germany.
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Morash BA, Imran A, Wilkinson D, Ur E, Wilkinson M. Leptin receptors are developmentally regulated in rat pituitary and hypothalamus. Mol Cell Endocrinol 2003; 210:1-8. [PMID: 14615055 DOI: 10.1016/j.mce.2003.09.003] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
We have previously reported that leptin is expressed in adult rat brain and pituitary gland, though the role of leptin in these sites has not been determined. Leptin mRNA is developmentally regulated in the brain and pituitary of male and female rats during early postnatal development, suggesting a role in the maturation of the brain-pituitary system. Here, we sought to extend our previous studies by evaluating (1) the ontogeny of leptin receptor mRNA levels in rat brain and pituitary and (2) pituitary leptin protein levels in neonatal and pre-pubertal rats. Pituitary leptin concentration was highest shortly after birth (postnatal day (PD) 4, 25 ng/mg protein) and fell significantly throughout postnatal development and into adulthood (PD 60, 3.5 ng/mg protein; P<0.005) coincident with a decline in pituitary leptin mRNA levels. Significant age-related effects on leptin receptor mRNA levels were also observed in the pituitary and the hypothalamus of male and female rats using semi-quantitative RT-PCR analysis. In the pituitary, the short form (OBRa) mRNA levels were highest in neonatal rats (PD 4) but declined throughout postnatal development (PD 4-22) paralleling the fall in pituitary leptin mRNA and protein levels. The long form (OBRb) mRNA levels were unaffected by age between PD 4 and 22. In contrast, hypothalamic, levels of OBRb mRNA were very low to undetectable shortly after birth (PD 4) and rose significantly between PD 4 and 14/22 while levels of OBRa mRNA were not significantly different between PD 4 and 22. Immunohistochemical detection of leptin receptor immunoreactivity (all forms) revealed the presence of OBR-like protein in pituitary and hypothalamus as early as PD 4. Cortical leptin receptor mRNA levels were similar throughout early postnatal development. No gender-related differences in leptin receptor mRNA levels were noted in brain or pituitary. In conclusion, these data, together with our previous work, indicate that the neonatal pituitary gland expresses leptin and leptin receptors at levels far in excess of those observed in mature rats. The pituitary is thus quite different from adipose tissue, hypothalamus and cerebral cortex, in which neonatal leptin expression is lowest at birth. Since neonatal pituitary leptin receptor expression is also elevated, it is possible that pituitary-derived leptin plays some role in the development of the hypothalamic-pituitary system.
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Affiliation(s)
- Barbara A Morash
- Department of Obstetrics, IWK Grace Health Centre, 5980 University Avenue, P.O. Box 3070, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada B3J 3G9
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Abstract
The unfolding of pubertal growth and maturation entails multisystem collaboration. Most notably, the outflow of gonadotropins and growth hormone (GH) proceeds both independently and jointly. The current update highlights this unique dependency in the human.
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Lahlou N, Issad T, Lebouc Y, Carel JC, Camoin L, Roger M, Girard J. Mutations in the human leptin and leptin receptor genes as models of serum leptin receptor regulation. Diabetes 2002; 51:1980-5. [PMID: 12031989 DOI: 10.2337/diabetes.51.6.1980] [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: 11/13/2022]
Abstract
A part of serum Ob leptin, an adipocyte-secreted peptide, is bound to a soluble Ob receptor (sObR). Immunoreactive sObR was measured in 125 lean or obese control subjects (group 1), 18 individuals with a mutation in the leptin gene impairing leptin secretion (group 2), and 10 individuals with a mutation in the ObR gene, leading to production of a truncated ObR not anchored to cell membranes (group 3). In group 1, sObR levels were negatively correlated with age and BMI in children and with BMI in adults. sObR levels were also negatively correlated with leptin levels. Leptin binding activity and sObR levels coeluted in gel-filtration chromatography. In group 2, sObR levels did not differ from those in lean control subjects and were not correlated with BMI. A single peak was detected in chromatographic fractions. In group 3, sObR levels were high and positively correlated with BMI. Immunoreactive sObR coeluted with leptin binding activity. These data demonstrate that leptin is not needed for ObR gene expression, and they suggest that leptin plays a role in receptor downregulation because sObR levels are negatively correlated with leptin levels and BMI in control subjects, whereas sObR levels are not depressed in obese leptin-deficient or leptin receptor-deficient individuals.
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Affiliation(s)
- Najiba Lahlou
- Hormone Biology, Saint-Vincent-de-Paul Hospital, Paris, France.
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Abstract
OBJECTIVE To review recent advances in understanding the role of leptin in the physiology and pathophysiology of reproduction, with a focus on relevant clinical situations. DESIGN A MEDLINE computer search was performed to identify relevant articles. RESULT(S) Leptin, an adipocyte hormone important in regulating energy homeostasis, interacts with the reproductive axis at multiple sites, with stimulatory effects at the hypothalamus and pituitary and inhibitory actions at the gonads. More recently, leptin has been shown to play a role in other target reproductive organs, such as the endometrium, placenta, and mammary gland, with corresponding influences on important physiologic processes such as menstruation, pregnancy, and lactation. As a marker of whether nutritional stores are adequate, leptin may act in concert with gonadotropins and the growth hormone axis to initiate the complex process of puberty. Conditions in which nutritional status is suboptimal, such as eating disorders, exercise-induced amenorrhea, and functional hypothalamic amenorrhea, are associated with low serum leptin levels; and conditions with excess energy stores or metabolic disturbances, such as obesity and polycystic ovarian syndrome, often have elevated serum or follicular fluid leptin levels, raising the possibility that relative leptin deficiency or resistance may be at least partly responsible for the reproductive abnormalities that occur with these conditions. CONCLUSION(S) Leptin may act as the critical link between adipose tissue and the reproductive system, indicating whether adequate energy reserves are present for normal reproductive function. Future interventional studies involving leptin administration are expected to further clarify this role of leptin and may provide new therapeutic options for the reproductive dysfunction associated with states of relative leptin deficiency or resistance.
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Affiliation(s)
- Stergios Moschos
- Division of Endocrinology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
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23
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Laird SM, Quinton ND, Anstie B, Li TC, Blakemore AI. Leptin and leptin-binding activity in women with recurrent miscarriage: correlation with pregnancy outcome. Hum Reprod 2001; 16:2008-13. [PMID: 11527914 DOI: 10.1093/humrep/16.9.2008] [Citation(s) in RCA: 40] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND Previous studies in humans and mice have suggested the importance of leptin in fetal growth. Recurrent miscarriage may be a result of abnormal placental and/or fetal development and therefore abnormal leptin levels may be associated with this form of pregnancy loss. METHODS Leptin and leptin-binding activity (LBA) were measured in blood obtained from women who had a history of recurrent miscarriage (n = 53) during weeks 5-6 and 7-8 of pregnancy, and the concentrations were correlated with subsequent pregnancy outcome. RESULTS Concentrations of leptin ranged from 1.4-62.8 ng/ml, but there was a strong correlation (r = 0.825, P < 0.001) between leptin values at weeks 5-6 and 7-8 in the same woman. Women who subsequently miscarried had significantly lower plasma leptin concentrations on both weeks 5-6 (13.34 +/- 2.1 ng/ml) (P < 0.05) and 7-8 (13.71 +/- 2.4 ng/ml) (P < 0.01) of pregnancy, than women who subsequently had a term birth (22.04 +/- 2.43 ng/ml week 5-6, 24.76 +/- 3.66 ng/ml week 7-8). LBA values ranged from 1-8.5% but there was no significant difference in LBA in blood obtained from women who subsequently miscarried or had a live birth. CONCLUSIONS The significantly lower concentrations of leptin in women who subsequently miscarried suggest that leptin may play a role in preventing miscarriage. However, as there was a considerable overlap between the values of leptin in women who subsequently miscarried, and those that had a live birth, these measurements are of limited use in the prediction of pregnancy outcome in these women.
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Affiliation(s)
- S M Laird
- Division of Biomedical Sciences/Biomedical Research Centre, Sheffield Hallam University, City Campus, Sheffield S1 1WB, UK.
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25
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Bartek J, Stejskal D, Stejskal P, Oral I. CONCENTRATION OF SOLUBLE LEPTIN RECEPTOR IN POPULATION. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2000. [DOI: 10.5507/bp.2000.012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
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Abstract
The diagnosis of central isosexual precocity, a condition much more common in girls than in boys, is currently viewed as a spectrum of disorders between isolated premature thelarche and borderline early puberty. In some countries, a trend may be seen toward onset of puberty at earlier ages. Integration of the clinical findings with bone age, pelvic echography, and hormonal data as well as follow-up ascertainment of progression of development is critical to define which patients should be proposed for therapy. The use of long-acting forms of gonadotropin-releasing hormone (GnRH) agonists may not be indicated in slowly progressive variants or borderline early puberty because they do not affect final height. Preservation of height potential is particularly obvious in precocious puberty starting at young ages. In some selected patients, associated growth hormone therapy may increase adult height but further studies are warranted. The psychosocial and behavioral correlates of precocious puberty are an important and under investigated area.
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Affiliation(s)
- M C Lebrethon
- Department of Pediatrics, C.H.U. Sart Tilman, Liège, Belgium
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27
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Kiess W, Müller G, Galler A, Reich A, Deutscher J, Klammt J, Kratzsch J. Body fat mass, leptin and puberty. J Pediatr Endocrinol Metab 2000; 13 Suppl 1:717-22. [PMID: 10969914 DOI: 10.1515/jpem.2000.13.s1.717] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Leptin, the ob gene product, provides a molecular basis for the lipostatic theory of the regulation of energy balance. Leptin circulates as a monomeric 16 kDa protein in rodent and human plasma and is also bound to leptin binding proteins that may form large high molecular weight complexes. Initial models of leptin action included leptin-deficient ob/ob mice and leptin-insensitive db/db mice. Peripheral or central administration of leptin reduced body weight, adiposity, and food intake in ob/ob mice but not in db/db mice. In ob/ob mice leptin treatment restored fertility. Leptin interacts with many messenger molecules in the brain. For example, leptin suppresses neuropeptide Y (NPY) expression in the arcuate nucleus. Increased NPY activity has an inhibitory effect on the gonadotropin axis and represents a direct mechanism for inhibiting sexual maturation and reproductive function in conditions of food restriction and/or energy expenditure. By modulating the hypothalamo-pituitary-gonadal axis both directly and indirectly, leptin may thus serve as the signal from fat to the brain about the adequacy of fat stores for pubertal development and reproduction. Normal leptin secretion is necessary for normal reproductive function to proceed and leptin may be a signal allowing for the point of initiation of and progression toward puberty.
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Affiliation(s)
- W Kiess
- Children's Hospital, University of Leipzig, Germany.
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Abstract
To successfully negotiate the developmental transition between youth and adulthood, adolescents must maneuver this often stressful period while acquiring skills necessary for independence. Certain behavioral features, including age-related increases in social behavior and risk-taking/novelty-seeking, are common among adolescents of diverse mammalian species and may aid in this process. Reduced positive incentive values from stimuli may lead adolescents to pursue new appetitive reinforcers through drug use and other risk-taking behaviors, with their relative insensitivity to drugs supporting comparatively greater per occasion use. Pubertal increases in gonadal hormones are a hallmark of adolescence, although there is little evidence for a simple association of these hormones with behavioral change during adolescence. Prominent developmental transformations are seen in prefrontal cortex and limbic brain regions of adolescents across a variety of species, alterations that include an apparent shift in the balance between mesocortical and mesolimbic dopamine systems. Developmental changes in these stressor-sensitive regions, which are critical for attributing incentive salience to drugs and other stimuli, likely contribute to the unique characteristics of adolescence.
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Affiliation(s)
- L P Spear
- Department of Psychology and Center for Developmental Psychobiology, Binghamton University, Binghamton, NY, USA.
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