The Oregon National Primate Research Center (ONPRC) at the Oregon Health &Science University (OHSU) proposes a Specialized Cooperative Center in Reproduction and Infertility Research (U54) that addresses the effects of hyperandrogenemia and obesity on female reproductive health. An interdisciplinary, translational program is designed to discern between the effects of excess androgen exposure and metabolic changes due to a typical Western-style diet (WSD, high fat and fructose content) on: (1) the hypothalamus-pituitary-ovary-reproductive tract axis, as well as adipose tissue;(2) the impact on fertility;and (3) if the treatment effects are reversible. Three research projects ue the nonhuman primate model, and one project focuses on the specific population of lean women with polycystic ovarian syndrome (PCOS). Project I, "Metabolic and Neuroendocrine Responses to Hyperandrogenemia and Diet", is directed by J. Cameron, via a consortium with the University of Pittsburgh and K. Grove at ONPRC. Project II, "Ovarian and Uterine Structure-Function: Influence of Androgen and Diet", is a collaboration between R. Stouffer and O. Slayden, ONPRC. Project III, "Effects of Androgen and Diet on Adipose Function," involves C. Roberts and colleagues at ONPRC. Project IV, "Androgen Excess as a Mechanism for Adipogenic Dysfunction in PCOS Women," incorporates a consortium with clinical experts (D. Dumesic, G. Chazenbalk) at the University of California, Los Angeles. Projects l-lll will be supported by a nonhuman primate (NHP) Core (O. Slayden, Supervisor) operating as a closed resource. This Core will maintain four treatment groups of young, female rhesus monkeys (controls, testosterone or T-treated, WSD-treated, and T + WSD) for four years, culminating in a fertility trial. In Year 05, reversibility of T and WSD actions will be examined. In addition, the Administrative Core (R. Stouffer, P.I.), and Outreach Core (D. Gordon and M. Zelinski) will promote interactions within and among SCCPIR Centers and increase public awareness and understanding of reproductive health research. Important, new information will accrue on the actions of androgen and diet-related factors, individually and in combination, relevant to the etiology and treatment of fertility disorders, such as PCOS.
The estimated prevalence of infertility in the human population is 9%, with recent evidence suggesting that hyperandrogenemia or obesity alone lead to reproductive dysfunction, and combine to further impair fertility. However, the causes versus effects of androgen, particularly as related to reproductive dysfunction, are controversial. Mechanistic studies in primates and lean PCOS women will discern between the roles of peripubertal androgen exposure and diet, and offer insight into improving therapy for infertility.
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