Hypothalamic Control of Puberty

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DESCRIPTION (provided by applicant): Understanding the mechanism of puberty is extremely important, as this developmental stage profoundly influences health and disease in adult life. The pubertal increase in steroid hormones modifies brain circuitry formation necessary for adolescent behaviors. Moreover, reproductive disorders, including precocious and delayed puberty and polycystic ovarian syndrome, and psychiatric disorders, such as manic-depression and schizophrenia, originate at this developmental stage. The overall objective of the parent grant is to investigate the role of the hypothalamus in the control of the onset of puberty. Over the course of 3 decades of studies supported by HD11355, the PI has noticed that there is a secular trend towards heavier bodyweight and younger ages of menarche in WNPRC colony monkeys. This trend is attributable to changes in the feeding program in the WNPRC and is strikingly similar to a recent secular trend towards obesity and accelerated age of menarche in human populations. Because the timing of puberty is closely associated with bodyweight changes, in this proposed study we will examine the possible epigenetic interaction between the mechanism of the onset of puberty and pubertal bodyweight increase in female rhesus monkeys, as a model for humans. The hypothesis to be tested is that a decrease in DNA methylation status of the luteinizing hormone-releasing hormone (LHRH) and/or KiSS-1 gene by excessive food intake triggers the onset of puberty in primates. Results from this study will not only provide a non-human primate model for obesity studies in humans and new insight into the mechanism of the onset of puberty in primates, but also enable us to retain a staff member who has relevant skills in molecular biology. In addition, the results from this study will provide information relevant to the health/husbandry of the WNPRC colony as well as all other NPRCs and center-like programs in non-human primate research. PUBLIC HEALTH RELEVANCE: Studying the mechanism of puberty is very important, as disorders associated with precocious and delayed puberty, and diseases such as polycystic ovarian syndrome, anorexia nervosa, manic- depression, and schizophrenia originate at or worsen with puberty. Because the proposed study addresses the underlying mechanism of bodyweight increase and puberty, the results will significantly impact our understanding of the current trend towards obesity and early puberty onset in our human society.