Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0848255 (female puberty)
 121 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lead (Pb) can delay sexual maturation; however, the mechanism and critical time of insult are not clearly defined. Therefore, we assessed maternal Pb levels during low-level gestational and/or lactational exposure, as well as blood and tissue Pb in developing fetuses in relation to the subsequent detrimental effects of Pb on puberty-related hormones and the onset of female puberty. Adult Fisher 344 female rats were gavaged daily with either a 1-ml solution of PbAc containing 12 mg/ml Pb or an equal volume of sodium acetate (NaCl), for the controls, from 30 days prior to breeding until their pups were weaned at 21 days. By cross-fostering at the time of birth, the pups were either exposed to PbAc or NaAc during gestation only, lactation only, or during both gestation and lactation. Pb delayed the timing of puberty and this delay was associated with suppressed serum levels of insulin-like growth factor-1 (IGF-1), luteinizing hormone (LH), and estradiol (E(2)). Liver IGF-1 mRNA was not affected, suggesting that Pb altered translation and/or secretion of IGF-1. We reported previously that peripherally derived IGF-1 acts at the hypothalamic level to facilitate LH release at puberty; hence, we suggest that the action of Pb in decreasing circulating IGF-1 contributes to the delayed puberty. The detrimental effects occurred regardless of the developmental time of exposure, although gestational exposure appeared more sensitive to the effects of Pb. Also, the effects noted were with blood Pb levels less than previously reported and these levels are relevant to human health concerns.
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PMID:Effects of lead (Pb) exposure during gestation and lactation on female pubertal development in the rat. 1222 May 94

Because prepubertal female rats maternally exposed to lead (Pb) exhibit suppressed serum levels of insulin-like growth factor-1 (IGF-1) and delayed puberty, we investigated the ability of centrally administered IGF-1 to stimulate luteinizing hormone (LH) release in vivo and LH-releasing hormone (LHRH) release in vitro from maternally Pb-exposed prepubertal female rats. Additionally, we assessed whether IGF-1 replacement could affect the timing of female puberty. Results demonstrated that IGF-1 stimulated significantly LH release in both control and Pb-exposed animals. When median eminences from control and Pb-exposed females were incubated with rat IGF-1 in vitro, they responded similarly with significant peptide-induced LHRH release. Lastly, we showed IGF-1 replacement reversed the delay in puberty caused by Pb. These results indicate the central LHRH response to IGF-1 is intact and that Pb-induced delayed puberty is due, at least in part, to suppressed circulating IGF-1 available to the hypothalamus.
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PMID:IGF-1 administration to prepubertal female rats can overcome delayed puberty caused by maternal Pb exposure. 1615 99

A cascade of neuroendocrine events regulates the initiation and progression of female puberty. However, the factors that determine the timing of these events across individuals are still uncertain. While the consequences of puberty on subsequent emotional development and adult behavior have received significant attention, what is less understood are the social and environmental factors that actually alter the initiation and progression of puberty. In order to more fully understand what factors influence pubertal timing in females, the present study quantified social and emotional behavior; stress physiology; and growth and activity measures in juvenile female rhesus monkeys to determine what best predicts eventual puberty. Based on previous reports, we hypothesized that increased agonistic behavior resulting from subordinate status in their natal group, in combination with slowed growth, reduced prosocial behavior, and increased emotional reactivity would predict delayed puberty. The analyses were restricted to behavioral and physiological measures obtained prior to the onset of puberty, defined as menarche. Together, our findings indicate that higher rates of aggression but lower rates of submission received from group mates; slower weight gain; and greater emotional reactivity, evidenced by higher anxiety, distress and appeasing behaviors, and lower cortisol responsivity in response to a potentially threatening situation, predicts delayed puberty. Together the combination of these variables accounted for 58% of the variance in the age of menarche, 71% in age at first ovulation, and 45% in the duration of adolescent sterility. While early puberty may be more advantageous for the individual from a fertility standpoint, it presents significant health risks, including increased risk for a number of estrogen dependent cancers and as well as the emergence of mood disorders during adulthood. On the other hand, it is possible that increased emotional reactivity associated with delayed puberty could persist, increasing the risk for emotional dysregulation to socially challenging situations. The data argue for prospective studies that will determine how emotional reactivity shown to be important for pubertal timing is affected by early social experience and temperament, and how these stress-related variables contribute to body weight accumulation, affecting the neuroendocrine regulation of puberty.
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PMID:Social and emotional predictors of the tempo of puberty in female rhesus monkeys. 2265 62

The timing of puberty is controlled by many genes. The elements coordinating this process have not, however, been identified. Here we show that an epigenetic mechanism of transcriptional repression times the initiation of female puberty in rats. We identify silencers of the Polycomb group (PcG) as principal contributors to this mechanism and show that PcG proteins repress Kiss1, a puberty-activating gene. Hypothalamic expression of two key PcG genes, Eed and Cbx7, decreased and methylation of their promoters increased before puberty. Inhibiting DNA methylation blocked both events and resulted in pubertal failure. The pubertal increase in Kiss1 expression was accompanied by EED loss from the Kiss1 promoter and enrichment of histone H3 modifications associated with gene activation. Preventing the eviction of EED from the Kiss1 promoter disrupted pulsatile gonadotropin-releasing hormone release, delayed puberty and compromised fecundity. Our results identify epigenetic silencing as a mechanism underlying the neuroendocrine control of female puberty.
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PMID:Epigenetic control of female puberty. 2343 74

The initiation of puberty is orchestrated by an augmentation of gonadotropin-releasing hormone (GnRH) secretion from a few thousand hypothalamic neurons. Recent findings have indicated that the neuroendocrine control of puberty may be regulated by a hierarchically organized network of transcriptional factors acting upstream of GnRH. These include enhanced at puberty 1 (EAP1), which contributes to the initiation of female puberty through transactivation of the GnRH promoter. However, no EAP1 mutations have been found in humans with disorders of pubertal timing. We performed whole-exome sequencing in 67 probands and 93 relatives from a large cohort of familial self-limited delayed puberty (DP). Variants were analyzed for rare, potentially pathogenic variants enriched in case versus controls and relevant to the biological control of puberty. We identified one in-frame deletion (Ala221del) and one rare missense variant (Asn770His) in EAP1 in two unrelated families; these variants were highly conserved and potentially pathogenic. Expression studies revealed Eap1 mRNA abundance in peri-pubertal mouse hypothalamus. EAP1 binding to the GnRH1 promoter increased in monkey hypothalamus at the onset of puberty as determined by chromatin immunoprecipitation. Using a luciferase reporter assay, EAP1 mutants showed a reduced ability to trans-activate the GnRH promoter compared to wild-type EAP1, due to reduced protein levels caused by the Ala221del mutation and subcellular mislocation caused by the Asn770His mutation, as revealed by western blot and immunofluorescence, respectively. In conclusion, we have identified the first EAP1 mutations leading to reduced GnRH transcriptional activity resulting in a phenotype of self-limited DP.
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PMID:EAP1 regulation of GnRH promoter activity is important for human pubertal timing. 3060 78

Childhood obesity, especially in girls, is frequently bound to earlier puberty, which is linked to higher disease burden later in life. The mechanisms underlying this association remain elusive. Here we show that brain ceramides participate in the control of female puberty and contribute to its alteration in early-onset obesity in rats. Postnatal overweight caused earlier puberty and increased hypothalamic ceramide content, while pharmacological activation of ceramide synthesis mimicked the pubertal advancement caused by obesity, specifically in females. Conversely, central blockade of de novo ceramide synthesis delayed puberty and prevented the effects of the puberty-activating signal, kisspeptin. This phenomenon seemingly involves a circuit encompassing the paraventricular nucleus (PVN) and ovarian sympathetic innervation. Early-onset obesity enhanced PVN expression of SPTLC1, a key enzyme for ceramide synthesis, and advanced the maturation of the ovarian noradrenergic system. In turn, obesity-induced pubertal precocity was reversed by virogenetic suppression of SPTLC1 in the PVN. Our data unveil a pathway, linking kisspeptin, PVN ceramides, and sympathetic ovarian innervation, as key for obesity-induced pubertal precocity.
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PMID:Central Ceramide Signaling Mediates Obesity-Induced Precocious Puberty. 3308 Feb 17