Ovarian 11β-Hydroxysteroid Dehydrogenase (11βHSD) Activity Is Suppressed in Women With Anovulatory Polycystic Ovary Syndrome (PCOS): Apparent Role for Ovarian Androgens

Context: Altered hepatic cortisol-cortisone metabolism by type 1 11β-hydroxysteroid dehydrogenase (11βHSD1) has previously been linked with polycystic ovary (PCO) syndrome (PCOS). Objectives: Our objectives were to establish whether ovarian 11βHSD activities are also altered in PCOS and to determine whether any changes in ovarian cortisol metabolism might reflect exposure to elevated concentrations of insulin or androgens. Design: Cortisol and cortisone concentrations were measured in follicular fluid aspirated from size-matched follicles dissected from normal, ovulatory, and anovulatory PCOs. Human granulosa-lutein cells, recovered during oocyte retrieval for assisted conception, were maintained in primary culture for 4 days, after which 11βHSD1 activities were measured as the net oxidation of [3H]cortisol (100 nmol/L) in the absence and presence of insulin (100 nmol/L) with or without metformin (1 μmol/L) or a range of androgens/oxy-androgen metabolites (0.01–10 μmol/L). Results: Intrafollicular cortiso...