Effect of ethanol on follicle stimulating hormone-induced steroidogenic acute regulatory protein (StAR) in cultured rat granulosa cells.
Effect of ethanol on follicle stimulating hormone-induced steroidogenic acute regulatory protein (StAR) in cultured rat granulosa cells.
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乙醇对培养的大鼠颗粒细胞中卵泡刺激素诱导的类固醇生成急性调节蛋白（StAR）的影响。
DOI：
10.1016/j.alcohol.2006.01.001
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Dees,WLes
中科院分区：
文献类型：
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作者：
Srivastava,VinodK;Vijayan,E;Hiney,JillK;Dees,WLes
甾体源性急性调节蛋白（StAR）在营养激素刺激的类固醇生物合成中起着关键作用，它通过促进胆固醇在线粒体膜上的转移，而细胞色素P450scc酶位于线粒体膜上，启动类固醇激素的生物合成。由于卵泡刺激素（FSH）是颗粒细胞中雌二醇（E2）合成的重要调节因子，并且由于已知乙醇可抑制促性腺激素刺激的卵巢类固醇生成，因此我们评估了乙醇对卵泡刺激素刺激的卵巢颗粒细胞StAR的影响。用妊娠母马血清促性腺激素预处理未成熟大鼠的颗粒细胞，在无血清培养基中，单独（仅培养基）或与FSH （25ng/ml）在存在或不存在乙醇（50mM）的情况下培养24小时。实时聚合酶链反应（PCR）分析显示，与仅接受培养基的细胞相比，fsh处理的细胞中StAR转录物的表达增加（p<0.01）。乙醇的存在阻断了StAR转录本对FSH的刺激（p<0.01）。这种效应与培养基中e2分泌的减少相一致。我们还研究了乙醇是否会影响环AMP （cAMP）的产生，cAMP是卵巢内介导促性腺激素作用的主要第二信使。FSH处理颗粒细胞显著增加cAMP水平（p<0.001），乙醇没有改变这一效应。重要的是，FSH诱导前列腺素E2（PGE2）释放增加（p<0.01），这一作用被乙醇阻断。Real-time PCR分析显示，乙醇对环氧合酶-1 （COX-1）的表达无影响，但能抑制fsh刺激下COX-2的表达（p<0.01）。这些结果表明，乙醇能够抑制fsh诱导的卵巢StAR，从而至少部分地通过抑制cox -2 - pge2途径抑制e2分泌。
Steroidogenic acute regulatory protein (StAR) plays a critical role in trophic hormone-stimulated steroid biosynthesis by facilitating the transfer of cholesterol across the mitochondrial membrane, where the cytochrome P450scc enzyme resides to initiate steroid hormone biosynthesis. Because follicle stimulating hormone (FSH) is a critically important regulator of estradiol (E2) synthesis in granulosa cells and because ethanol is known to suppress gonadotropin-stimulated ovarian steroidogenesis, we evaluated the effects of ethanol on FSH-stimulated StAR in ovarian granulosa cells. Granulosa cells from immature rats pretreated with pregnant mare serum gonadotropin were cultured for 24h in serum-free medium, either alone (medium only) or with FSH (25ng/ml) in the presence or absence of ethanol (50mM). Real-time polymerase chain reaction (PCR) analysis showed increased (p<0.01) expression of the StAR transcript in FSH-treated cells, when compared with cells that received medium only. The FSH stimulation of StAR transcript was blocked (p<0.01) by the presence of ethanol. This effect coincided with a decrease in E2secretion into the culture medium. We also examined whether ethanol could affect the production of cyclic AMP (cAMP), the main second messenger that mediates gonadotropin action within the ovary. FSH treatment of granulosa cells markedly increased (p<0.001) cAMP levels, an effect that was not altered by ethanol. Importantly, FSH induced an increase (p<0.01) in the release of prostaglandin E2(PGE2), an effect that was blocked by ethanol. Real-time PCR analysis showed that ethanol had no effect on the expression of cyclooxygenase-1 (COX-1), but blocked (p<0.01) FSH-stimulated expression of COX-2. These results demonstrate that ethanol is capable of inhibiting FSH-induced ovarian StAR and thus, contributing to suppressed E2secretion, at least in part, through an inhibitory action on the COX-2–PGE2pathway.