THE OVARIAN CONTRIBUTION TO PERIPHERALLY DERIVED SERUM C-19 CONJUGATES

While serum markers of peripheral androgen metabolism, such as 5-alpha-androstane-3-alpha,17-beta-diol glucuronide (3-alpha-diolG) and androsterone glucuronide (AoG), have been highly correlated with adrenal androgen production, the relative ovarian contribution to the pool of various C19 conjugates has not been fully investigated. Our hypothesis was that whereas the ovary may not produce C19 conjugates directly, ovarian androgens, such as testosterone (T) and androstenedione (A), may be used as substrate for peripheral production of these conjugates. To determine whether the ovary contributes directly to the pool of C19 conjugates, blood was obtained from the ovarian and peripheral veins of eight normal women (NW) at hysterectomy. To assess the indirect ovarian contribution to C19 conjugate production, the effect of ovarian suppression and stimulation on circulating 3-alpha-diol and Ao conjugate levels was examined in 10 NW and 10 anovulatory nonhirsute patients with PCO (NH-PCO). Ovarian suppression was carried out with leuprolide acetate (1 mg, sc) daily until the serum estradiol level was 30 pg/mL and was continued thereafter during ovarian stimulation with im human menopausal gonadotropin or FSH. Blood samples were taken before, during, and after GnRH agonist suppression and just before hCG stimulation. Both unconjugated and conjugated androgens were quantified in serum by specific RIAs. No peripheral-ovarian gradients were found for 3-alpha-diol or Ao sulfates (3-alpha-diolS or AoS) or glucuronides. In the NH-PCO group, both T and A levels were elevated, and they were suppressed significantly to levels similar those in NW. With stimulation, T and A levels rose significantly to higher levels than those observed in NW. Both AoS and 3-alpha-diolS, but not AoG and 3-alpha-diolG, decreased significantly with agonist suppression in the two groups; the decrease in levels of AoS and T correlated significantly in the NH-PCO group. With stimulation, the Ao and 3-alpha-diol conjugate levels increased significantly in NH-PCO and were most marked for Ao S and 3-alpha-diol S, which were previously suppressed; the increase in AoG and A correlated highly. Our data suggest that while there is no evidence for the direct ovarian production of C19 conjugates, these markers of peripheral androgen action are influenced by precursors from the ovary, principally A and T.