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. Recent studies demonstrated a positive association between relative androgenic hormonal milieu in postmenopausal women and the occurrence of metabolic syndrome (MBS) and cardiovascular disease (CVD). Furthermore, the inflexional rise in the incidence of ovarian cancer in the postmenopausal years and the predominance of androgen receptors in these ovarian surface epithelium-derived neoplasms also suggests an association with testosterone (T). Therefore, experiments were designed to test the hypothesis that chronic (2 year) exposure of young peripubertal female macaques to elevated T levels will be associated with physical and biochemical symptoms of MBS, indices associated with CV disease, and morphological markers of ovarian neoplasm. We will perform these experiments through an extension of a study (U54 HD018185- Project IV) that is currently being conducted at ONPRC. Eight peripubertal female macaques are exposed to elevated T levels starting before puberty (12 months) and continuing to post-menarche (36 months). Effects will be compared to the control (cholesterol-treated) group of six age-matched female macaques.
Our specific aims will determine if chronic exposure to an androgenic (elevated T) milieu leads to: 1. Physical (e.g., visceral adiposity) and biochemical (e.g., altered insulin sensitivity) features of MBS. 2. Indices of the inflammatory (e.g., C-reactive protein) and procoagulant (e.g., PAI-1) state associated with CVD. 3. Histological changes in the ovarian surface epithelium (e.g., inclusion cysts) predisposing it to neoplasm.
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