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)

The possibility of an alteration in the age at which pubertal onset occurs has shown that we still lack knowledge on the molecular and physiological mechanisms of normal female puberty. In this study, the adjustment effects of different suckling and prepuberty nutrition on puberty onset and the expression of hypothalamic Kiss1/kisspeptin and gonadotrophin-releasing hormone (GnRH) were examined in 1-day-old female Sprague-Dawley rats. Animals were randomly assigned according to different suckling nutritional challenges (different milk intake before weaning) and prepuberty nutritional challenges (different food supply after weaning) into four groups: overnutrition group 1, overnutrition group 2 (O2), normal group (N, control group), and malnutrition group (M). In situ hybridization, Western blot analysis, and immunohistochemistry were used to analyze the expression of hypothalamic Kiss1/kisspeptin and GnRH. In the O1 group, GnRH and Kiss1/kisspeptin levels in the hypothalamus peaked at an early age, while malnutrition resulted in a delay in the GnRH and Kiss1/kisspeptin peaks. This study indicated that nutrition greatly affected the sexual development of female rats and that the effects of suckling nutrition were much greater than those of prepuberty nutrition.
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PMID:The effect of different nutritional states on puberty onset and the expression of hypothalamic Kiss1/kisspepetin. 2345 11

Puberty is regulated by epigenetic mechanisms and is highly sensitive to metabolic and nutritional cues. However, the epigenetic pathways mediating the effects of nutrition and obesity on pubertal timing are unknown. Here, we identify Sirtuin 1 (SIRT1), a fuel-sensing deacetylase, as a molecule that restrains female puberty via epigenetic repression of the puberty-activating gene, Kiss1. SIRT1 is expressed in hypothalamic Kiss1 neurons and suppresses Kiss1 expression. SIRT1 interacts with the Polycomb silencing complex to decrease Kiss1 promoter activity. As puberty approaches, SIRT1 is evicted from the Kiss1 promoter facilitating a repressive-to-permissive switch in chromatin landscape. Early-onset overnutrition accelerates these changes, enhances Kiss1 expression and advances puberty. In contrast, undernutrition raises SIRT1 levels, protracts Kiss1 repression and delays puberty. This delay is mimicked by central pharmacological activation of SIRT1 or SIRT1 overexpression, achieved via transgenesis or virogenetic targeting to the ARC. Our results identify SIRT1-mediated inhibition of Kiss1 as key epigenetic mechanism by which nutritional cues and obesity influence mammalian puberty.
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PMID:SIRT1 mediates obesity- and nutrient-dependent perturbation of pubertal timing by epigenetically controlling Kiss1 expression. 3030 20