Matteri R K, Stanczyk F Z, Cassidenti D L, Paulson R J, Lobo R A
Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles 90033.
J Clin Endocrinol Metab. 1992 Sep;75(3):768-72. doi: 10.1210/jcem.75.3.1387653.
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.
虽然外周雄激素代谢的血清标志物，如5α-雄甾烷-3α，17β-二醇葡萄糖醛酸苷（3α-二醇G）和雄酮葡萄糖醛酸苷（AoG），与肾上腺雄激素的产生高度相关，但卵巢对各种C19共轭物池的相对贡献尚未得到充分研究。我们的假设是，虽然卵巢可能不直接产生C19共轭物，但卵巢雄激素，如睾酮（T）和雄烯二酮（A），可能用作这些共轭物外周产生的底物。为了确定卵巢是否直接对C19共轭物池有贡献，在子宫切除术中从8名正常女性（NW）的卵巢静脉和外周静脉采集血液。为了评估卵巢对C19共轭物产生的间接贡献，在10名NW和10名患有多囊卵巢综合征的无排卵非多毛患者（NH-PCO）中检查了卵巢抑制和刺激对循环3α-二醇和Ao共轭物水平的影响。每天用醋酸亮丙瑞林（1mg，皮下注射）进行卵巢抑制，直到血清雌二醇水平为30pg/mL，此后在用人绝经期促性腺激素或FSH进行卵巢刺激期间继续进行。在GnRH激动剂抑制前、抑制期间和抑制后以及hCG刺激前采集血样。通过特异性放射免疫分析法对血清中未结合和结合的雄激素进行定量。未发现3α-二醇或Ao硫酸盐（3α-二醇S或AoS）或葡萄糖醛酸苷存在外周-卵巢梯度。在NH-PCO组中，T和A水平均升高，并且它们被显著抑制至与NW组相似的水平。在刺激下，T和A水平显著升高至高于NW组观察到的水平。两组中，AoS和3α-二醇S（而非AoG和3α-二醇G）在激动剂抑制后显著降低；在NH-PCO组中，AoS和T水平的降低显著相关。在刺激下，NH-PCO组中Ao和3α-二醇共轭物水平显著升高，对于先前被抑制的AoS和3α-二醇S最为明显；AoG和A的升高高度相关。我们的数据表明，虽然没有证据表明卵巢直接产生C19共轭物，但这些外周雄激素作用的标志物受来自卵巢的前体物质（主要是A和T）的影响。
