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 ovary syndrome (PCOS) is among the most common endocrine disorders of premenopausal women, affecting 7% of this population. It has substantial reproductive and metabolic morbidities. This project supports Aim 3 of NIH/NICHD U54 HD034449. We have identified a potential biochemical phenotype of elevated dehydroepiandrosterone sulfate (DHEAS) levels in the brothers of PCOS probands. It is our hypothesis that hyperandrogenemia in the sisters of PCOS probands is due to a defect in ovarian and adrenal steroidogenesis and that elevated DHEAS levels may reflect the same defect in affected male relatives. We plan to assess adrenal steroidogenic responses to ACTH in the brothers of PCOS probands. Further, it may be the case that subtle abnormalities in testicular steroidogenesis can be unmasked with provocative testing of potentially affected male relatives. We will investigate this with GnRH analog testing. We will also determine whether brothers have similar gene expression patterns to their PCOS proband sisters.
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