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A cross-cultural examination of the relationship between ages at menarche, marriage, and first birth

Udry JR, Cliquet RL

Demography, 1982 Feb;19(1):53-63.
PMID: 7067870

Recent work with samples of black and white urban American women showed a clear behavioral sequence relating age at menarche to age at first intercourse to age at first birth. This paper shows that the linking of ages at menarche, intercourse, marriage, and first birth is a pattern which occurs in very diverse cultures. We present confirmatory data from the United States, Belgium, and Pakistan, and from Malay and Chinese women in Malaysia. We interpret our findings as indicating a biological process leading to (a) social interpretations of readiness for reproduction, and (b) persisting biological differences between early and late maturing women.

Matched MeSH terms: Sexual Maturation*
The Sertoli cell of the water buffalo--an electron microscopic study

Azmi TI, Bongso TA, Harisah M, Basrur PK

Can. J. Vet. Res., 1990 Jan;54(1):93-8.
PMID: 2306676

The ultrastructure of Sertoli cells in the seminiferous tubules of water buffaloes before and during sexual maturity was studied by transmission electron microscopy, with emphasis on the intranucleolar vesicular elements. Sertoli cells of animals under 12 months of age were distinguished from the germ cells by the presence of electron dense membrane bound bodies within their cytoplasm. These cells, referred to as basal indifferent supporting cells, were probably involved in the phagocytosis and elimination of degenerating spermatocytes, which failed to differentiate into spermatids and spermatozoa in animals under one year of age. In 12 month old animals, a few Sertoli cells exhibiting the vesicular elements appeared in the nucleolar region while in animals over 15 months of age Sertoli cells could be positively identified by the characteristic cytoplasm containing microtubules, elongated and electron dense mitochondria, extensive granular endoplasmic reticulum and the presence of spermatids in various stages of spermiogenesis. The vesicular elements in the nucleolar region of the Sertoli cells were most prominent at this stage. Ultrastructural features of the Sertoli cells revealed an abundance of ribosome-like particles surrounding the vesicles of varying size. Some of these vesicular elements contained amorphous material suggesting that they represent the products sequestered in the nuclear region for transport to the cytoplasm and that the process of spermiogenesis may be dependent on the ability of Sertoli cells to generate these products at sexual maturity.

Matched MeSH terms: Sexual Maturation/physiology
Fulltext Genetic and environmental effects on age at menarche, and its relationship with reproductive health in twins

Jahanfar S, Lye MS, Krishnarajah IS

Indian J Hum Genet, 2013 Apr;19(2):245-50.
PMID: 24019629 DOI: 10.4103/0971-6866.116127

INTRODUCTION: Menarche or first menstrual period is a landmark in reproductive life span and it is the most prominent change of puberty. The timing of menarche can be under the influence of genes as well as individual environmental factors interacting with genetic factors.
OBJECTIVE: Our study objectives were (a) to investigate the heritability of age of menarche in twins, (b) to obtain the association between age of menarche and childhood factors, and reproductive events/behavior, (c) to examine whether or not having a male co-twin affects early/late menarche.
METHODOLOGY: A group of female-female identical (n = 108, 54 pairs), non-identical twins (n = 68, 34 pairs) and 17 females from opposite-sex twin sets were identified from twin registries of Malaysia and Iran. Genetic analysis was performed via two methods of Falconers' formula and maximum likelihood.
RESULTS: Heritability was found to be 66% using Falconers' formula and 15% using univariate twin analysis. Model analysis revealed that shared environmental factors have a major contribution in determining the age of menarche (82%) followed by non-shared environment (18%).
DISCUSSION: Result of this study is consistent with that of the literature. Timing of menarche could be under the influence of shared and non-shared environmental effects. Hirsutism was found to have a higher frequency among subjects with late menarche. There was no significant difference in age of menarche between females of opposite-sex twins and females of same-sex twins.
CONCLUSION: It is concluded that twin models provide a powerful means of examining the total genetic contribution to age of menarche. Longitudinal studies of twins may clarify the type of environmental effects that determine the age of menarche.

Matched MeSH terms: Sexual Maturation
Fulltext Vaginal and Cervical Agenesis – Hysterectomy in A Young Girl.

Roszaman Ramli, Ghazali Ismail

International Medical Journal Malaysia, 2006;5(2):1-8.
MyJurnal

Vaginal agenesis is a rare event occurring at a frequency of 1 case per 4000-10 000 female lives born. The most common etiology of vaginal agenesis is congenital absence of the uterus and vagina called mullerian agenesis (Mayer-Rokitansky-Hauser Syndrome). Although most patients with mullerian agenesis have small rudimentary 2 ‘mullerian bulbs’ without any endometrial activity, 7-8% of these cases possibly have a functioning uterus 3. In vaginal agenesis, genetic females are thought to have persistence of mullerian inhibiting factor MIF, resulting in failure of the vagina and uterus to develop 4. The ovaries, given their separate embryonic source, are normal in structure and function. This condition usually goes undetected until these patients reach puberty, when they start to experience cyclic pelvic pain due to the accumulation of menstrual blood.

Matched MeSH terms: Sexual Maturation
Fulltext Turner syndrome with ring x chromosome: do they have a distinct phenotype?

Lee, Yee Lin, Salwati Shuib, Wu, Loo Ling

International Medical Journal Malaysia, 2018;17(3):99-102.
MyJurnal

In contrast to classic Turner syndrome, Turner patients with ring X chromosome are associated with distinct dysmorphism and are likely to be mentally impaired. Four Turner patients with ring X chromosome were examined for phenotypic features of Turner syndrome and additional dysmorphism. Both patients 1 and 2 are twins with normal intelligence whereas patients 3 and 4 have mental impairment. With the exception of patient 4, the other three patients only have few Turner characteristics. None of the patients have the distinctive dysmorphism previously reported in Turner syndrome with ring X chromosome. Both twins developed spontaneous puberty. Patients 3 and 4 however had no spontaneous puberty. We postulate that this variation may be related to the ring size, the proportion of 45,X and ring X chromosome in cell lines of various body tissues as well as the ability of these rings to be inactivated as a result of lyonisation.

Matched MeSH terms: Sexual Maturation
Fulltext Urinary Sex Steroids and Anthropometric Markers of Puberty - A Novel Approach to Characterising Within-Person Changes of Puberty Hormones

Singh GK, Balzer BW, Kelly PJ, Paxton K, Hawke CI, Handelsman DJ, et al.

PLoS One, 2015;10(11):e0143555.
PMID: 26599397 DOI: 10.1371/journal.pone.0143555

The longitudinal relationships of within-individual hormone and anthropometric changes during puberty have not ever been fully described. The objectives of this study were to demonstrate that 3 monthly urine collection was feasible in young adolescents and to utilise liquid chromatography-tandem mass spectrometry assay methods for serum and urine testosterone (T), estradiol (E2) and luteinizing hormone (LH) in adolescents by relating temporal changes in urine and serum hormones over 12 months to standard measures of pubertal development.

Matched MeSH terms: Sexual Maturation/physiology
Fulltext Spawning seasons of Rasbora tawarensis (Pisces: Cyprinidae) in Lake Laut Tawar, Aceh province, Indonesia

Muchlisin ZA, Musman M, Azizah MN

Reprod Biol Endocrinol, 2010;8:49.
PMID: 20482777 DOI: 10.1186/1477-7827-8-49

Rasbora tawarensis is an endemic freshwater fish in Lake Laut Tawar, Aceh Province, Indonesia. Unfortunately, its status is regarded as critical endangered with populations decreasing in recent years. To date no information on the spawning activities of the fish are available. Therefore, this study provides a contribution to the knowledge on reproductive biology of R. tawarensis especially on spawning seasons as well as basic information for conservation of the species.

Matched MeSH terms: Sexual Maturation/physiology
Survey of sickness in Singapore with notes on births, deaths, handicapped persons, puberty, menopause, immunisation, incidence of cough and adoption

LLOYD DAVIES TA, MILLS R

Med J Malaya, 1961 Mar;15:117-56.
PMID: 14466048
Matched MeSH terms: Sexual Maturation*
Neonatal dexamethasone exposure down-regulates GnRH expression through the GnIH pathway in female mice

Soga T, Dalpatadu SL, Wong DW, Parhar IS

Neuroscience, 2012 Aug 30;218:56-64.
PMID: 22626647 DOI: 10.1016/j.neuroscience.2012.05.023

Synthetic glucocorticoid (dexamethasone; DEX) treatment during the neonatal stage is known to affect reproductive activity. However, it is still unknown whether neonatal stress activates gonadotropin-inhibitory hormone (GnIH) synthesizing cells in the dorsomedial hypothalamus (DMH), which could have pronounced suppressive action on gonadotropin-releasing hormone (GnRH) neurons, leading to delayed pubertal onset. This study was designed to determine the effect of neonatal DEX (1.0mg/kg) exposure on reproductive maturation. Therefore, GnRH, GnIH and GnIH receptors, G-protein coupled receptors (GPR) 147 and GPR74 mRNA levels were measured using quantitative real-time PCR in female mice at postnatal (P) days 21, 30 and in estrus stage mice, aged between P45-50. DEX-treated females of P45-50 had delayed vaginal opening, and irregular estrus cycles and lower GnRH expression in the preoptic area (POA) when compared with age-matched controls. The expression levels of GPR147 and GPR74 mRNA in the POA increased significantly in DEX-treated female mice of P21 and P45-50 compared to controls. In addition, GPR147 and GPR74 mRNA expression was observed in laser captured single GnRH neurons in the POA. Although there was no difference in GnIH mRNA expression in the DMH, immunostained GnIH cell numbers in the DMH increased in DEX-treated females of P45-50 compared to controls. Taken together, the results show that the delayed pubertal onset could be due to the inhibition of GnRH gene expression after neonatal DEX treatment, which may be accounted for in part by the inhibitory signals from the up-regulated GnIH-GnIH receptor pathway to the POA.

Matched MeSH terms: Sexual Maturation/drug effects*; Sexual Maturation/physiology
Fulltext A "Timed" Kiss Is Essential for Reproduction: Lessons from Mammalian Studies

Putteeraj M, Soga T, Ubuka T, Parhar IS

Front Endocrinol (Lausanne), 2016;7:121.
PMID: 27630616 DOI: 10.3389/fendo.2016.00121

Reproduction is associated with the circadian system, primarily as a result of the connectivity between the biological clock in the suprachiasmatic nucleus (SCN) and reproduction-regulating brain regions, such as preoptic area (POA), anteroventral periventricular nucleus (AVPV), and arcuate nucleus (ARC). Networking of the central pacemaker to these hypothalamic brain regions is partly represented by close fiber appositions to specialized neurons, such as kisspeptin and gonadotropin-releasing hormone (GnRH) neurons; accounting for rhythmic release of gonadotropins and sex steroids. Numerous studies have attempted to dissect the neurochemical properties of GnRH neurons, which possess intrinsic oscillatory features through the presence of clock genes to regulate the pulsatile and circadian secretion. However, less attention has been given to kisspeptin, the upstream regulator of GnRH and a potent mediator of reproductive functions including puberty. Kisspeptin exerts its stimulatory effects on GnRH secretion via its cognate Kiss-1R receptor that is co-expressed on GnRH neurons. Emerging studies have found that kisspeptin neurons oscillate on a circadian basis and that these neurons also express clock genes that are thought to regulate its rhythmic activities. Based on the fiber networks between the SCN and reproductive nuclei such as the POA, AVPV, and ARC, it is suggested that interactions among the central biological clock and reproductive neurons ensure optimal reproductive functionality. Within this neuronal circuitry, kisspeptin neuronal system is likely to "time" reproduction in a long term during development and aging, in a medium term to regulate circadian or estrus cycle, and in a short term to regulate pulsatile GnRH secretion.

Matched MeSH terms: Sexual Maturation
Fulltext Quality of Life in Children with Disorders of Sex Development

M Selveindran N, Syed Zakaria SZ, Jalaludin MY, Rasat R

Horm Res Paediatr, 2017;88(5):324-330.
PMID: 28965114 DOI: 10.1159/000478780

BACKGROUND/AIMS: Disorders of sex development (DSD) are a heterogeneous group of rare conditions. Evidence-based treatment is challenged by a lack of clinical longitudinal outcome studies. We sought to investigate the quality of life of children with DSD other than congenital adrenal hyperplasia.
METHODS: The participants (aged 6-18 years) were 23 patients raised as males and 7 patients raised as females. Control data were obtained from representatives of the patients' siblings matched for age and gender. The Pediatric Quality of Life InventoryTM Version 4.0 (PedsQL) Generic Core Scales were used as the study tool.
RESULTS: In comparison with the reference data, the patient group had significantly lower overall PedsQL (p < 0.01) and school functioning (p < 0.01) scores. Also, the total PedsQL score was significantly lower in patients with DSD who were of female social sex as compared to the controls who were females. Family income, surgical procedures, degree of virilization, and mode of puberty did not influence the PedsQL scores.
CONCLUSION: This study revealed a poorer quality of life for patients with DSD as compared to the age-matched control group. This highlights the need for a skilled multidisciplinary team to manage this group of patients.

Matched MeSH terms: Sexual Maturation
Fulltext Lentinula edodes Cultured Extract and Rouxiella badensis subsp. acadiensis (Canan SV-53) Intake Alleviates Immune Deregulation and Inflammation by Modulating Signaling Pathways and Epigenetic Mechanisms

Shahbazi R, Yasavoli-Sharahi H, Alsadi N, Sharifzad F, Fang S, Cuenin C, et al.

Int J Mol Sci, 2023 Sep 27;24(19).
PMID: 37834058 DOI: 10.3390/ijms241914610

Puberty is a critical developmental period of life characterized by marked physiological changes, including changes in the immune system and gut microbiota development. Exposure to inflammation induced by immune stressors during puberty has been found to stimulate central inflammation and lead to immune disturbance at distant sites from the gut; however, its enduring effects on gut immunity are not well explored. Therefore, in this study, we used a pubertal lipopolysaccharides (LPS)-induced inflammation mouse model to mimic pubertal exposure to inflammation and dysbiosis. We hypothesized that pubertal LPS-induced inflammation may cause long-term dysfunction in gut immunity by enduring dysregulation of inflammatory signaling and epigenetic changes, while prebiotic/probiotic intake may mitigate the gut immune system deregulation later in life. To this end, four-week-old female Balb/c mice were fed prebiotics/probiotics and exposed to LPS in the pubertal window. To better decipher the acute and enduring immunoprotective effects of biotic intake, we addressed the effect of treatment on interleukin (IL)-17 signaling related-cytokines and pathways. In addition, the effect of treatment on gut microbiota and epigenetic alterations, including changes in microRNA (miRNA) expression and DNA methylation, were studied. Our results revealed a significant dysregulation in selected cytokines, proteins, and miRNAs involved in key signaling pathways related to IL-17 production and function, including IL-17A and F, IL-6, IL-1β, transforming growth factor-β (TGF-β), signal transducer and activator of transcription-3 (STAT3), p-STAT3, forkhead box O1 (FOXO1), and miR-145 in the small intestine of adult mice challenged with LPS during puberty. In contrast, dietary interventions mitigated the lasting adverse effects of LPS on gut immune function, partly through epigenetic mechanisms. A DNA methylation analysis demonstrated that enduring changes in gut immunity in adult mice might be linked to differentially methylated genes, including Lpb, Rorc, Runx1, Il17ra, Rac1, Ccl5, and Il10, involved in Th17 cell differentiation and IL-17 production and signaling. In addition, prebiotic administration prevented LPS-induced changes in the gut microbiota in pubertal mice. Together, these results indicate that following a healthy diet rich in prebiotics and probiotics is an optimal strategy for programming immune system function in the critical developmental windows of life and controlling inflammation later in life.

Matched MeSH terms: Sexual Maturation
Fulltext Associations between socio-demographic characteristics and pubertal status with disordered eating among primary school children in Selangor, Malaysia

Chong LS, Chin YS, Gan WY, Nasir MT

Asia Pac J Clin Nutr, 2017 Mar;26(2):326-333.
PMID: 28244713 DOI: 10.6133/apjcn.012016.10

BACKGROUND AND OBJECTIVES: To determine the associations between socio-demographic characteristics and pubertal status with disordered eating among primary school children.
METHODS AND STUDY DESIGN: Using a stratified multi-stage sampling, a total of 816 children (282 boys and 534 girls) aged 10 to 11 years from 12 selected primary schools in the state of Selangor, participated in this study. Data were collected on socio-demographic characteristics, pubertal status and disordered eating behaviors. The Pubertal Development Scale and the Children's Eating Attitudes Test (ChEAT) were used to assess pubertal status and disordered eating, respectively. Logistic regression analysis was conducted to determine the risk factors of disordered eating.
RESULTS: The prevalence of disordered eating was 30.8% (32.8% in boys and 29.7% in girls). However, the sex difference in the prevalence was not statistically significant. Age, ethnicity and pubertal status were significantly associated with disordered eating in univariate logistic regression analysis. Multivariate logistic regression analysis showed that among boys, being either in an advanced or post-pubertal stage (adjusted OR=8.64) and older age group (adjusted OR=2.03) were risk factors of disordered eating. However, among girls, being a Malay (adjusted OR=3.79) or Indian (adjusted OR=5.04) in an advanced or post-pubertal stage (adjusted OR=2.34) and older age group (adjusted OR=1.53) were risk factors of disordered eating.
CONCLUSION: This study found one in three children had disordered eating. Since ethnicity and pubertal status were identified as risk factors, ethnicity-specific intervention programs on the prevention of disordered eating among children should take into consideration their pubertal status.

Matched MeSH terms: Sexual Maturation
Fulltext Insulin-like growth factor-I and fast growth-hormone levels in mild and moderately malnourished children

Wan Nazaimoona WM, Osman A, Ng ML, Tan TT, Wu LL, Sakinah O, et al.

Asia Pac J Clin Nutr, 1992 Dec;1(4):207-10.
PMID: 24323236

Insulin-like growth factor-I (IGF-I)and fasting growth hormone levels were measured in a group of 255 children (163 males and 92 females. age ranged 6-17 years) of varying pubertal development and body mass index (BMI); well-nourished (BMI> 18). mildly-malnourished (BMI = 15-18) and moderately-malnourished (BMI<15). In well-nourished children IGF-I levels increased significantly (P = 0.02) with pubertal development. where girls at Tanner 5 had significantly higher (p = 0.03) IGF-I levels than the boys. Whilst there was no change in fasting GH levels with nutritional status, IGF-I levels of prepubertal boys and girls decreased significantly with BMI (P<0.001 and P = 0.01 respectively). Hence. measurement of IGF-I levels is a sensitive biochemical index in the assessment of mild and moderate form of malnutrition in prepubertal children.

Matched MeSH terms: Sexual Maturation
Assessment of pubertal development in juvenile male rats after sub-acute exposure to bisphenol A and nonylphenol

Tan BL, Kassim NM, Mohd MA

Toxicol Lett, 2003 Aug 28;143(3):261-70.
PMID: 12849686

The effects of bisphenol A and nonylphenol on pubertal development in the intact juvenile/peripubertal male Sprague-Dawley rats was observed in this study from PND23-52/53. Two groups of rats were administered orally with either 100 mg/kg body weight of nonylphenol or bisphenol A. Another group of rats were administered orally with a mixture of 100 mg/kg body weight of nonylphenol and bisphenol A. Control group was administered with the vehicle of Tween-80 with corn oil (1:9 v/v). Observations made in this study included growth, age at preputial separation, thyroid, liver, testis and kidney weight and histology, epididymal and seminal vesicle plus coagulation gland weight. Nonylphenol and bisphenol A have been observed to cause delay in puberty onset as well as testicular damage in the treatment groups when compared to the control; spermatogenesis was affected in most treated rats. Bisphenol A also caused the enlargement of the kidney and hydronephrosis. Administration of nonylphenol and bisphenol A as a mixture has caused less than additive effects.

Matched MeSH terms: Sexual Maturation/drug effects*
Identification and relative abundances of mRNA for a gene encoding the vWD domain and three Kazal-type domains in the ovary of giant freshwater prawns, Macrobrachium rosenbergii

Faiz ZM, Mardhiyyah MP, Mohamad A, Hidir A, Nurul-Hidayah A, Wong L, et al.

Anim. Reprod. Sci., 2019 Oct;209:106143.
PMID: 31514941 DOI: 10.1016/j.anireprosci.2019.106143

Understanding Macrobrachium rosenbergii ovarian maturation control at the genome level is an important aspect for increasing larvae production. In this study, an ovarian maturation related gene, M. rosenbergii vWD domain and three Kazal-type domains of a gene (MrvWD-Kazal) have been studied. The MrvWD-Kazal gene was isolated using a rapid amplification of cDNA end (RACE) method and the relative abundances of MrvWD-Kazal mRNA in the ovary, hepatopancreas, stomach, intestine and gill were determined by using the quantitative PCR technique. The MrvWD-Kazal gene is composed of 2194 bp with an open reading frame (ORF) of 1998 bp encoding 665 amino acids and has great similarity to the M. nipponense vWD-Kazal gene (91%). The qPCR analyses indicated the relative abundance of MrvWD-Kazal mRNA transcript varied among different stages of ovarian function (P < 0.05), but there were no differences abundance in hepatopancreas, stomach, intestine and gill (P> 0.05). In the ovary, relative abundance of MrvWD-Kazal mRNA transcript gradually increased with ovarian maturation from Stages 1 (Spent; 1.00-fold), to 2 (Proliferative; 3.47-fold) to 3 (Premature; 6.18-fold) and decreased at Stage 4 (Mature; 1.31-fold). Differential relative abundances of MrvWD-Kazal mRNA transcript in the ovary indicate the MrvWD-Kazal protein may have an important function in ovarian maturation of M. rosenbergii. The results of this study also indicate the MrvWD-Kazal is not involved in regulation of the reproductive related function of the hepatopancreas, digestive system (stomach and intestine) and respiratory system (gill).

Matched MeSH terms: Sexual Maturation/genetics
Fulltext Transcriptome Analysis and Differential Gene Expression on the Testis of Orange Mud Crab, Scylla olivacea, during Sexual Maturation

Waiho K, Fazhan H, Shahreza MS, Moh JH, Noorbaiduri S, Wong LL, et al.

PLoS One, 2017;12(1):e0171095.
PMID: 28135340 DOI: 10.1371/journal.pone.0171095

Adequate genetic information is essential for sustainable crustacean fisheries and aquaculture management. The commercially important orange mud crab, Scylla olivacea, is prevalent in Southeast Asia region and is highly sought after. Although it is a suitable aquaculture candidate, full domestication of this species is hampered by the lack of knowledge about the sexual maturation process and the molecular mechanisms behind it, especially in males. To date, data on its whole genome is yet to be reported for S. olivacea. The available transcriptome data published previously on this species focus primarily on females and the role of central nervous system in reproductive development. De novo transcriptome sequencing for the testes of S. olivacea from immature, maturing and mature stages were performed. A total of approximately 144 million high-quality reads were generated and de novo assembled into 160,569 transcripts with a total length of 142.2 Mb. Approximately 15-23% of the total assembled transcripts were annotated when compared to public protein sequence databases (i.e. UniProt database, Interpro database, Pfam database and Drosophila melanogaster protein database), and GO-categorised with GO Ontology terms. A total of 156,181 high-quality Single-Nucleotide Polymorphisms (SNPs) were mined from the transcriptome data of present study. Transcriptome comparison among the testes of different maturation stages revealed one gene (beta crystallin like gene) with the most significant differential expression-up-regulated in immature stage and down-regulated in maturing and mature stages. This was further validated by qRT-PCR. In conclusion, a comprehensive transcriptome of the testis of orange mud crabs from different maturation stages were obtained. This report provides an invaluable resource for enhancing our understanding of this species' genome structure and biology, as expressed and controlled by their gonads.

Matched MeSH terms: Sexual Maturation/genetics*
Specific research programmes in Sri Lanka and Malaysia

WHO Offset Publ, 1983.
PMID: 6677001
Matched MeSH terms: Sexual Maturation
Fulltext Leptin: a pleitropic factor in physiology

Fayez A Almabhouh, Faizatul Isyraqiah Ahmad Muhammad, Hisham Ibrahim, Harbindarjeet Singh

Journal of Clinical and Health Sciences, 2019;4(2):31-57.
MyJurnal

Leptin, a 16 kDa protein and a product of the ob/ob gene, has a tertiary structure similar to that
of a cytokine. It is primarily secreted by white adipose tissue and its levels in the blood correlate
positively with percentage body fat. Leptin was first identified in 1994 as a major factor that
regulated food intake and energy balance. Leptin in the circulation exists either as a free
monomeric hormone or bound to its soluble receptor. Its serum levels usually range from 0.5 to
37.7 ng/ml in males and 2.0 to 45.2 ng/ml in females. The half-life of leptin is between 20 - 30
minutes and it is eliminated mainly by the kidneys. However, research over the last 25 years
has revealed numerous other physiological roles for leptin, including roles in inflammation,
immune function, neuro-endocrine function, bone metabolism, blood pressure regulation and
sexual maturation. Most of these roles have been identified from studies on leptin deficient
rodents. Apart from energy balance and sexual maturation, where its role is direct and obvious,
its actions on the rest of the other systems are permissive. Actions of leptin are both centrally
and peripherally mediated involving receptors that are widely distributed in the body. Six leptin
receptor isoforms, belonging to the class 1 cytokine receptor family, have been identified.
These receptors are products of the OBR gene. The cellular actions of leptin are mediated
through any one of five different signalling pathways that include the JAK-STAT, PI3K, MAPK,
AMPK, and the mTOR signalling pathways.

Matched MeSH terms: Sexual Maturation
Fulltext The physiology of leptin: revisited

Singh, Harbindar Jeet

Medical Health Reviews, 2009;2009(1):95-133.
MyJurnal

Leptin, a 167 amino-acid product of the ob or LEP gene, was first reported in 1994 after a 40-year search that began following the emergence of a mutant strain of mice with hyperphagia, early on-set obesity, and delayed sexual maturation. Since then, leptin deficiency has also been reported in the rat, and more recently in humans. It is secreted constitutively primarily by the white adipose tissue, and in smaller quantities by a number of non-adipose tissues. It acts by binding to specific membrane bound leptin receptors, belonging to the class 1 cytokine receptor family, and activating the JAK-STAT system. Leptin regulates appetite and body weight mainly through its actions on the hypothalamus involving the NPYmelanocortin pathway, and, to a lesser extent, through increased energy expenditure by way of sympathoactivation and increased substrate cycling. Its effects on reproduction, puberty in particular, are mediated through actions on the hypothalamic-pituitary-gonadal axis and on the gonads. Leptin also appears to have permissive roles in CNS development during the neonatal period, bone growth and development, and in haemopoietic and immune functions. Although it was its deficiency state that first led to its discovery, it now appears that the clinical significance of leptin lies not only in the consequences of its deficiency but also when it is in excess as occurs in obesity. Emerging evidence is implicating leptin as a link between obesity associated cardiovascular disease risks and infertility. Besides this, leptin is also being implicated as a growth factor in cancer. The story that started with a search for a body weight regulating factor is now unfolding into one that is revealing roles for leptin that stretch beyond the regulation of appetite and body weight.

Matched MeSH terms: Sexual Maturation

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