Gilling-Smith C, Willis D S, Beard R W, Franks S
Department of Obstetrics and Gynecology, St. Mary's Hospital Medical School, Imperial College of Science, Technology, and Medicine, London, United Kingdom.
J Clin Endocrinol Metab. 1994 Oct;79(4):1158-65. doi: 10.1210/jcem.79.4.7962289.
The aim of this study was to examine the hypothesis that hypersecretion of ovarian androgens in polycystic ovary syndrome results from an intrinsic abnormality of androgen biosynthesis by thecal cells. Steroid accumulation by human thecal cells from normal and polycystic ovaries (PCO-theca) was examined under basal and LH-stimulated conditions. A method for dispersing and culturing human thecal cells as primary monolayers in serum-free medium was developed. LH increased androstenedione (A), progesterone (P), 17 alpha-hydroxyprogesterone, dehydroepiandrosterone, and estradiol accumulation in the overlying medium in a dose-dependent manner at a maximum effective dose of 2.5 ng/mL. The principal variables affecting the magnitude of steroid accumulation were plating density, duration of incubation, and follicle size. Using only theca from follicles less than 10 mm and keeping plating density constant, 48-h steroid production by theca from five normal ovaries was compared to that from nine polycystic ovaries isolated from both anovulatory and ovulatory women. There was a significant increase in both basal (median, 32.1 pmol/1000 cells.48 h; range, 18.7-250) and LH-stimulated (56 pmol/1000 cells; range, 40.7-406) A accumulation by PCO-theca compared to basal (1.7 pmol/1000 cells; range, 1.1-4.3) and LH-stimulated (2.8 pmol/1000 cells; range, 2.0-8.1) A accumulation by normal theca, with no overlap in values between the two. Although P production was also increased in the PCO-theca, the A to P ratios under both basal and LH-stimulated conditions were significantly higher in the PCO-theca [A/P ratio normal; PCO basal, 0.1 and 0.53 (P < 0.01); LH-stimulated, 0.04 and 0.65 (P < 0.001)], suggesting increased conversion of P to A. The steroid response to LH was similar in both groups. This is the first report of a difference in thecal androgen production between normal and polycystic ovaries and supports the hypothesis that there is a primary abnormality in the regulation of androgen production in PCOS.
多囊卵巢综合征中卵巢雄激素分泌过多是由卵泡膜细胞雄激素生物合成的内在异常所致。在基础和促黄体生成素（LH）刺激条件下，检测了来自正常卵巢和多囊卵巢（PCO-卵泡膜）的人卵泡膜细胞的类固醇积累情况。开发了一种在无血清培养基中将人卵泡膜细胞分散并培养为原代单层细胞的方法。LH以剂量依赖方式增加了上层培养基中雄烯二酮（A）、孕酮（P）、17α-羟孕酮、脱氢表雄酮和雌二醇的积累，最大有效剂量为2.5 ng/mL。影响类固醇积累量的主要变量是接种密度、孵育时间和卵泡大小。仅使用来自小于10 mm卵泡的卵泡膜，并保持接种密度恒定，比较了来自五个正常卵巢的卵泡膜与来自无排卵和有排卵女性的九个多囊卵巢的卵泡膜在48小时内的类固醇产生情况。与正常卵泡膜基础状态下（1.7 pmol/1000细胞；范围，1.1-4.3）和LH刺激状态下（2.8 pmol/1000细胞；范围，2.0-8.1）的A积累相比，PCO-卵泡膜基础状态下（中位数，32.1 pmol/1000细胞·48小时；范围，18.7-250）和LH刺激状态下（56 pmol/1000细胞；范围，40.7-406）的A积累显著增加，两组数值无重叠。虽然PCO-卵泡膜中的P产生也增加，但在基础和LH刺激条件下，PCO-卵泡膜中A与P的比值显著更高（正常A/P比值；PCO基础状态下，0.1和0.53（P<0.01）；LH刺激状态下，0.04和0.65（P<0.001）），表明P向A的转化增加。两组对LH的类固醇反应相似。这是关于正常卵巢和多囊卵巢卵泡膜雄激素产生差异的首次报道，并支持了多囊卵巢综合征中雄激素产生调节存在原发性异常的假设。
