ANDROGEN EXPOSURE AND ACTIONS IN PRE- TO PERIPUBERTAL MONKEYS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Polycystic Ovarian Syndrome (PCOS) is a common disorder of hyperandrogenism and oligo/anovulation, causing infertility in 4-8% of American women. The etiology of PCOS remains controversial. Though insulin resistance is considered one cause of PCOS, correlative evidence suggests that exposure to increased levels of androgens (from the ovaries) before and during puberty may be a primary cause of many PCOS symptoms. The goal of this project is to determine whether chronic exposure to elevated levels of testosterone (T), found in adolescent girls predisposed to PCOS, will cause changes in the neuroendocrine-ovarian axis in peri-pubertal female rhesus macaques that are reminiscent of PCOS. Ovarian parameters include age at menarche, occurrence of normal menstrual cycles, and numbers/sizes of antral follicles in the ovaries. Neuroendocrine indices will include the frequency and amplitude of circulating luteinizing hormone (LH) pulses secreted by the pituitary gland, sensitivity of LH secretion to exogenous gonadotropin-releasing hormone (GnRH), and steroid (exogenous progesterone) feedback inhibition of LH secretion after menarche. This project will greatly increase our knowledge of the effects of elevated androgen exposure in female adolescents, and possibly develop a primate model for better understanding of the causes, prevention and treatment of PCOS in women.