Augmented androgen production is a stable steroidogenic phenotype of propagated theca cells from polycystic ovaries
Augmented androgen production is a stable steroidogenic phenotype of propagated theca cells from polycystic ovaries
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DOI：
10.1210/me.13.6.946
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发表时间：
1999-06-01
影响因子：
--
通讯作者：
McAllister, JM
中科院分区：
文献类型：
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作者：
Nelson, VL;Legro, RS;McAllister, JM
为了验证与多囊卵巢综合征（PCOS）相关的高雄激素血症是由于卵巢卵泡细胞类固醇生成的内在异常引起的假设，我们在长期培养中检测了正常和多囊卵巢综合征卵泡细胞的类固醇激素分泌、类固醇生成酶活性和mRNA表达。孕酮（P4）、17 α -羟孕酮（17OHP4）和睾酮(T)在PCOS卵泡膜细胞培养中显著增加。此外，基础和福斯克林刺激的孕烯醇酮、P4和脱氢表雄酮代谢在PCOS卵泡膜细胞中显著增加。PCOS的卵泡细胞能够将前体代谢为T，这反映了雄激素17 β -羟基类固醇脱氢酶的表达。与正常细胞相比，forskolin刺激的胆固醇侧链切割酶（CYP11A）和17 α -羟化酶/17,20-去糖化酶（CYP17）表达增加，而甾体源性急性调节蛋白mRNA表达无差异。总的来说，这些观察结果表明，增加的CYP11A和CYP17 mRNA表达，以及增加的CYP17、3 β -羟基类固醇脱氢酶和17 β -羟基类固醇脱氢酶活性，从而增加P4、17OHP4和T的产生，是PCOS卵泡膜细胞的稳定特性。这些发现与多囊卵巢综合征鞘细胞的类固醇生成活性存在内在改变的概念是一致的，这种改变包括生物合成途径中的多个步骤。
To test the hypothesis that the hyperandrogenemia associated with polycystic ovary syndrome (PCOS) results from an intrinsic abnormality in ovarian theca cell steroidogenesis, we examined steroid hormone production, steroidogenic enzyme activity, and mRNA expression in normal and PCOS theca cells propagated in long-term culture. Progesterone (P4), 17 alpha-hydroxyprogesterone (17OHP4), and testosterone (T) production per cell were markedly increased in PCOS theca cell cultures. Moreover, basal and forskolin-stimulated pregnenolone, P4, and dehydroepiandrosterone metabolism were increased dramatically in PCOS theca cells. PCOS theca cells were capable of substantial metabolism of precursors into T, reflecting expression of an androgenic 17 beta-hydroxysteroid dehydrogenase. Forskolin-stimulated cholesterol side chain cleavage enzyme (CYP11A) and 17 alpha-hydroxylase/17,20-desmolase (CYP17) expression were augmented in PCOS theca cells compared with normal cells, whereas no differences were found in steroidogenic acute regulatory protein mRNA expression. Collectively, these observations establish that increased CYP11A and CYP17 mRNA expression, as well as increased CYP17, 3 beta-hydroxysteroid dehydrogenase, and 17 beta-hydroxysteroid dehydrogenase enzyme activity per theca cell, and consequently increased production of P4, 17OHP4, and T, are stable properties of PCOS theca cells. These findings are consistent with the notion that there is an intrinsic alteration in the steroidogenic activity of PCOS thecal cells that encompasses multiple steps in the biosynthetic pathway.