White D, Leigh A, Wilson C, Donaldson A, Franks S
Department of Obstetrics and Gynaecology, St Mary's Hospital Medical School, London, UK.
Clin Endocrinol (Oxf). 1995 May;42(5):475-81. doi: 10.1111/j.1365-2265.1995.tb02665.x.
A previously published study has identified that anovulatory women with PCOS have an increased response of 17 alpha-hydroxyprogesterone (17OHP) and androstenedione to a GnRH analogue suggesting dysregulation of cytochrome P450c17 alpha. The object of this study was to compare the responses of the pituitary-ovarian axis to a single dose of a long-acting GnRH agonist (GnRHa) in both ovulatory and anovulatory women with PCOS with those in normal subjects.
Comparative study of responses of LH, FSH and ovarian steroids to buserelin and the adrenal steroid response to synthetic ACTH in two groups of women with hyperandrogenaemia and polycystic ovaries: those with anovulatory menses or amenorrhoea and those with equally elevated serum testosterone concentrations but regular menses. Results in both groups of women with PCO were compared with those in normal subjects.
Twenty-four women with hyperandrogenism and PCO (14 had oligo or amenorrhoea, 10 regular cycles) and 12 weight matched controls with normal ovaries, regular cycles and neither clinical nor biochemical evidence of hyperandrogenism. Subjects were given synthetic ACTH (Synacthen) 250 micrograms i.v. on day 1 of the study and blood collected at 30 and 60 minutes thereafter. On the evening of day 1, dexamethasone treatment was commenced to suppress adrenal androgens. GnRHa 100 micrograms s.c. was given on day 2 and blood samples collected at 30-minute intervals for 4 hours and once more at 24 hours after the injection.
The acute responses of both immunoactive and bioactive LH to GnRHa were significantly greater in the ovulatory PCO group (ovPCO) than controls but the response was greater in anovulatory women with polycystic ovaries (anovPCO) than in either ovPCO or controls, throughout the 24-hour study period. Despite the discrepancy in LH concentrations, basal serum concentrations of androstenedione were equally elevated in anovulatory and ovulatory women with PCO, compared with controls. There was a small but significant increase in androstenedione following GnRHa in both PCO groups at 24 hours but not in controls. A similar pattern was observed in the response of 17OHP to GnRHa although the response was significantly higher than controls in anovPCO women only. By contrast, the responses of both androstenedione and 17OHP to 250 micrograms synthetic ACTH were similar in PCO women to those in controls.
These data provide evidence for ovarian hypersecretion of androgens in ovulatory, as well as anovulatory women with PCO, supporting the concept of abnormal regulation of 17-hydroxylase and (17,20-lyase activity in the ovary. The finding of an equal degree of hyperandrogenaemia in ovPCO and anovPCO groups, even though LH levels were much higher in the latter, suggests that hypersecretion of LH is not the primary cause of ovarian hyperandrogenism. Hyperandrogenism in PCOs may therefore represent an intrinsic abnormality of ovarian theca-interstitial cell function.
一项先前发表的研究已确定，患有多囊卵巢综合征（PCOS）的无排卵女性对促性腺激素释放激素（GnRH）类似物的17α-羟孕酮（17OHP）和雄烯二酮反应增强，提示细胞色素P450c17α调节异常。本研究的目的是比较患有PCOS的排卵和无排卵女性以及正常受试者垂体-卵巢轴对单剂量长效GnRH激动剂（GnRHa）的反应。
对两组高雄激素血症和多囊卵巢女性中促黄体生成素（LH）、促卵泡生成素（FSH）和卵巢类固醇对布舍瑞林的反应以及肾上腺类固醇对合成促肾上腺皮质激素（ACTH）的反应进行比较研究：一组为无排卵性月经或闭经患者，另一组血清睾酮浓度同样升高但月经规律。将两组PCO女性的结果与正常受试者的结果进行比较。
24名患有高雄激素血症和PCO的女性（14名月经稀发或闭经，10名月经周期规律）以及12名体重匹配的对照者，对照者卵巢正常、月经周期规律，且无高雄激素血症的临床及生化证据。在研究第1天，受试者静脉注射250微克合成ACTH（辛纳科），并于注射后30分钟和60分钟采集血样。在第1天晚上，开始地塞米松治疗以抑制肾上腺雄激素。在第2天皮下注射100微克GnRHa，并在注射后4小时内每隔30分钟采集血样一次，注射后24小时再采集一次。
在整个24小时研究期间，排卵型PCO组（ovPCO）中免疫活性和生物活性LH对GnRHa的急性反应均显著高于对照组，但多囊卵巢无排卵女性（anovPCO）的反应高于ovPCO组和对照组。尽管LH浓度存在差异，但与对照组相比，无排卵和排卵型PCO女性的基础血清雄烯二酮浓度均同样升高。在24小时时，两组PCO女性在GnRHa注射后雄烯二酮均有小幅但显著的升高，而对照组无此变化。17OHP对GnRHa的反应也观察到类似模式，不过仅anovPCO女性的反应显著高于对照组。相比之下，PCO女性中雄烯二酮和17OHP对250微克合成ACTH的反应与对照组相似。
这些数据为排卵型以及无排卵型PCO女性卵巢雄激素分泌过多提供了证据，支持卵巢中17-羟化酶和（17,20-裂解酶活性调节异常的概念。ovPCO组和anovPCO组雄激素血症程度相同，尽管后者LH水平高得多，这表明LH分泌过多不是卵巢雄激素过多的主要原因。因此，PCO中的雄激素过多可能代表卵巢卵泡膜-间质细胞功能的内在异常。
