Troglitazone inhibits progesterone production in porcine granulosa cells
Troglitazone inhibits progesterone production in porcine granulosa cells
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DOI：
10.1210/en.139.12.4962
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发表时间：
1998-12-01
期刊：
影响因子：
4.8
通讯作者：
Urban, RJ
中科院分区：
文献类型：
--
作者：
Gasic, S;Bodenburg, Y;Urban, RJ
曲格列酮（一种改善胰岛素抵抗的噻唑烷二酮）降低多囊卵巢综合征患者升高的雄激素浓度。在这项研究中，我们评估了曲格列酮对猪颗粒细胞类固醇合成的直接影响。曲格列酮以剂量和时间依赖性方式抑制孕酮产生（最早作用于4 h，最大作用于24 h），而不影响细胞活力。在存在25-羟基胆固醇的情况下，曲格列酮也抑制了孕酮的产生，表明该药物不影响细胞内胆固醇转运。曲格列酮也抑制FSH和毛喉素刺激的孕酮分泌。孕酮产量的减少伴随着双烯醇酮浓度的明显升高，表明3 β-羟基类固醇脱氢酶（BP-HSD）的抑制。与对照组相比，24 h后，曲格列酮处理颗粒细胞中3 β-HSD的活性降低了60%以上。Troglitazone没有。影响猪颗粒细胞中芳香化酶的活性。总之，曲格列酮对猪颗粒细胞类固醇生成有直接影响。该药物特异性抑制3 β-HSD活性，导致孕酮产生受损。这种对类固醇合成的直接体外作用的临床相关性需要进一步研究。
Troglitazone (a thiazolidinedione that improves insulin resistance) lowers elevated androgen concentrations in women with polycystic ovarian syndrome. In this study, we assessed the direct effects of troglitazone on steroidogenesis in porcine granulosa cells. Troglitazone inhibited progesterone production in a dose- and time-dependent manner (earliest effects at 4 h, maximum at 24 h) without affecting cell viability. Progesterone production was also inhibited by troglitazone in the presence of 25-hydroxycholesterol, indicating that the drug does not affect intracellular cholesterol transport. Troglitazone also inhibited FSH- and forskolin-stimulated progesterone secretion. The reduced progesterone production was accompanied by narked elevations of pregnenolone concentrations, suggesting inhibition of 3 beta-hydroxysteroid dehydrogenase (BP-HSD). The activity of 3 beta-HSD in troglitazone-treated granulosa cells was decreased by more than 60%, compared with controls after 24 h. Troglitazone did not. affect aromatase activity in porcine granulosa cells. In summary, troglitazone has direct effects on porcine granulosa cell steroidogenesis. The drug specifically inhibits 3 beta-HSD activity, resulting in impaired progesterone production. The clinical relevance of this direct in vitro effect on steroidogenesis needs further investigation.