The goal of the Center for Reproductive Science and Medicine is to develop understanding of the mechanisms that govern normal and disordered function of the hypothalamic-pituitary-ovarian axis. This application represents our renewal for year 25 and our productivity has been outstanding over the most recent granting period with 86 papers published. We will continue to produce novel and important contributions to the reproductive sciences, integrating multidisciplinary clinical and basic research to facilitate and accelerate the translation of promising new discoveries into clinical medicine. We have chosen three innovative and complementary Research Projects, all with experienced, internationally renowned leaders. We will address the hormonal control of the gonadotropin beta-subunit genes in the pituitary, focusing on regulation by activin, GnRH, and steroid hormones. The emphasis will be on understanding the synergy and interdependence between these hormones in controlling transcription in model immortalized gonadotrope cells and genetically modified mice. We will chart new territory in the role of metabolic homeostasis in infertility. A broad based, in vivo and in vitro approach is proposed to elucidate the mechanisms of insulin, adiponectin and PPAR gamma action in impaired reproductive function, using novel animal models and immortalized hypothalamic GnRH-secreting immortalized neurons and gonadotrope cells. We will focus on the influence of gonadal steroids and insulin in the endocrine control of the ovarian granulosa cells in vivo in normal women and patients with polycystic ovary syndrome [PCOS], addressing fundamental mechanisms underlying PCOS. All three projects have teams of highly experienced investigators and all three Project Leaders serve as Co-investigators on at least one other component of the Center. These three projects are highly interactive and synergistic and create a coherent mechanistic and translational program for the Center. The only core will be the Administrative Core. The Administrative Core facilitates and supports all of the activities of the Center and provides the Enrichment Program. It also houses the Human Ovary Tissue Bank, which provides well-characterized human ovary tissue to all NIH-funded investigators in North America.
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