A mechanism for the suppression of estrogen production in polycystic ovary syndrome
A mechanism for the suppression of estrogen production in polycystic ovary syndrome
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DOI：
10.1210/jc.81.10.3686
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发表时间：
1996-10-01
影响因子：
5.8
通讯作者：
Magoffin, DA
中科院分区：
文献类型：
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作者：
Agarwal, SK;Judd, HL;Magoffin, DA
在多囊卵巢综合征（PCOS）中，卵泡发育在早期窦期停止，此时颗粒细胞（GC）模具中的芳香化酶表达正常发生。尽管卵泡内雄烯二酮和生物活性FSH浓度高，体内雌激素生物合成仍然很低。当来自PCOS卵泡的GC在体外用FSH刺激时，发生显著的雌激素产生刺激，表明PCOS卵泡含有雌激素产生的内源性抑制剂。为了验证这一假设，在雄烯二酮（10（-6）mol/L）的存在下，将来自过度刺激妇女的GC与来自PCOS和正常周期对照妇女的卵泡液（FF）进行培养。对照组妇女的FF引起雌二醇产生小幅下降（20%）。PCOS FF引起剂量相关的雌二醇产生抑制（60%），表明PCOS FF的抑制活性明显更强。为了确定雄激素代谢异常是否在抑制PCOS患者雌二醇产生中发挥作用，我们测定了对照组和PCOS患者血清和FF中的5 α-雄甾烷-3，17-二酮（一种芳香化酶活性的竞争性抑制剂）。PCOS患者血清中5 α-雄甾烷-3，17-二酮水平显著升高。PCOS FF中的5 α-雄甾烷-3，17-二酮水平比血清高1000倍。PCOS卵泡中FF水平显著高于正常优势卵泡和群组卵泡（P < 0.0001）。剂量反应研究显示，正常优势卵泡FF中5 α-雄甾烷-3，17-二酮的浓度（79.4 +/- 14.6 nmol/L）对雌二醇的产生几乎没有影响。相比之下，PCOS FF中的5 α-雄甾烷-3，17-二酮水平（581.6 +/- 62.9 nmol/L）抑制了75%的雌二醇产生。这些数据支持PCOS FF含有一种或多种芳香化酶活性的内源性抑制剂的假设，并表明PCOS FF中异常高的5 α-雄甾烷-3，17-二酮水平可能是雌二醇产生的重要抑制剂。
In polycystic ovary syndrome (PCOS), follicle development arrests in the early antral stage when aromatase expression in the granulosa cells (GC) mould normally occur. Despite high intrafollicular concentrations of androstenedione and bioactive FSH, in vivo estrogen biosynthesis remains low. When GC from PCOS follicles are stimulated with FSH in vitro, a marked stimulation of estrogen production occurs, suggesting that PCOS follicles contain an endogenous inhibitor of estrogen production. To test this hypothesis, GC from hyperstimulated women were cultured with increasing concentrations of follicular fluid (FF) from PCOS and normally cycling control women in the presence of androstenedione (10(-6) mol/L). FF from control women caused a small decrease (20%) in estradiol production. PCOS FF caused a dose-related inhibition of estradiol production (60%), indicating that there was significantly more inhibitory activity in PCOS FF. To determine whether abnormal androgen metabolism could play a role in inhibiting estradiol production in PCOS, we measured 5 alpha-Androstane-3,17-dione, a competitive inhibitor of aromatase activity, in serum and FF of control and PCOS women. 5 alpha-Androstane-3,17-dione levels in serum were significantly elevated in PCOS. 5 alpha-Androstane-3,17-dione levels were 1000-fold higher in PCOS FF than serum. Moreover, FF levels were markedly higher in PCOS follicles (P < 0.0001) than in normal dominant and cohort follicles. Dose-response studies revealed that the concentration of 5 alpha-androstane-3,17-dione present in FF from normal dominant follicles (79.4 +/- 14.6 nmol/L) had little effect on estradiol production. In contrast, 5 alpha-androstane-3,17-dione levels in PCOS FF (581.6 +/- 62.9 nmol/L) inhibited estradiol production by 75%. These data support the hypothesis that PCOS FF contains one or more endogenous inhibitors of aromatase activity and suggest that abnormally high 5 alpha-androstane-3,17-dione levels in PCOS FF may be an important inhibitor of estradiol production.