The biochemical basis for increased testosterone production in theca cells propagated from patients with polycystic ovary syndrome
The biochemical basis for increased testosterone production in theca cells propagated from patients with polycystic ovary syndrome
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DOI：
10.1210/jc.86.12.5925
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发表时间：
2001-12-01
影响因子：
5.8
通讯作者：
McAllister, JM
中科院分区：
文献类型：
--
作者：
Nelson, VL;Qin, KN;McAllister, JM
多囊卵巢综合征（PCOS）患者的卵巢卵泡膜细胞比正常卵泡膜细胞更有效地将类固醇前体转化为T。为了确定PCOS卵泡膜细胞增加T产生的基础，我们检测了从正常和PCOS卵巢分离的卵泡膜和颗粒细胞的长期培养物中I-V型17 β-羟基类固醇脱氢酶（17 β HSD）亚型的表达。RT-PCR分析表明卵泡膜细胞表达醛酮还原酶（AKR）超家族成员V型17 β HSD（17 β HSDV，AKR 1C 3），而表达短链脱氢酶/还原酶超家族成员I、II和IV型17 β HSD仅限于颗粒细胞。III型17 β HSD，睾丸亚型，未检测到颗粒或卵泡膜细胞。北方和实时荧光PCR分析表明，17 β HSDV转录本在PCOS卵泡膜细胞与正常卵泡膜细胞相比没有显着增加。RT-PCR分析显示，卵泡膜细胞还表达另一种AKR，20 α HSD（AKR 1C 1）。与正常卵泡膜细胞相比，PCOS卵泡膜细胞中基础和毛喉素刺激的20 α HSD mRNA水平均升高。然而，在PCOS中，每个卵泡膜细胞的17 β HSD酶活性并没有显著增加，这表明AKR 1C 3和AKR 1C 1在这种情况下都不有助于T的形成。相反，17 α-羟化酶/C17，20裂解酶和3 β HSD酶活性在PCOS卵泡膜细胞中升高，驱动T前体的产生增加。这些发现表明：1）PCOS卵泡膜细胞中T产生的增加不是由于“雄激素性”17 β HSD活性的失调或可能表达17 β HSD活性的AKR的表达改变所致;和2）T前体的合成增加是驱动PCOS中T分泌增加的主要因素。
Ovarian theca cells propagated from patients with polycystic ovary syndrome (PCOS) convert steroid precursors into T more efficiently than normal theca cells. To identify the basis for increased T production by PCOS theca cells, we examined type I-V 17 beta -hydroxysteroid dehydrogenase (17 beta HSD) isoform expression in long-term cultures of theca and granulosa cells isolated from normal and PCOS ovaries. RT-PCR analysis demonstrated that theca cells express type V 17 beta HSD a member of the aldo-keto reductase (AKR) superfamily (17 beta HSDV, AKR1C3), whereas expression of type I, II, and IV 17 beta HSD, which are members of the short-chain dehydrogenase/reductase superfamily, was limited to granulosa cells. Type III 17 beta HSD, the testicular isoform, was not detected in either granulosa or theca cells. Northern and real-time PCR analyses demonstrated that 17 beta HSDV transcripts were not significantly increased in PCOS theca cells compared with normal theca cells. RT-PCR analysis revealed that theca cells also express another AKR, 20 alpha HSD (AKR1C1). Both basal and forskolin-stimulated 20 alpha HSD mRNA levels were increased in PCOS theca cells compared with normal theca cells. However, 17 beta HSD enzyme activity per theca cell was not significantly increased in PCOS, suggesting that neither AKR1C3 nor AKR1C1 contributes to the formation of T in this condition. In contrast, 17 alpha -hydroxyIase/C17,20 lyase and 3 beta HSD enzyme activities were elevated in PCOS theca cells, driving increased production of T precursors. These findings indicate that 1) increased T production in PCOS theca cells does not result from dysregulation of "androgenic" 17 beta HSD activity or altered expression of AKRs that may express 17 beta HSD activity; and 2) increased synthesis of T precursors is the primary factor driving enhanced T secretion in PCOS.