Corticotropin-releasing hormone stimulates the expression of the steroidogenic acute regulatory protein in MA-10 mouse cells
Corticotropin-releasing hormone stimulates the expression of the steroidogenic acute regulatory protein in MA-10 mouse cells
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DOI：
10.1095/biolreprod57.3.547
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发表时间：
1997-09-01
影响因子：
3.6
通讯作者：
Norman, RL
中科院分区：
文献类型：
--
作者：
Huang, BM;Stocco, DM;Norman, RL
我们以前已经证明，促肾上腺皮质激素释放激素（CRH）治疗MA-10小鼠Leydig肿瘤细胞的结果在剂量依赖性刺激孕酮的生产。鉴于这一观察结果，我们希望确定CRH对这些细胞中类固醇生成急性调节（星星）蛋白合成的影响。星星是一种类固醇生成的组织特异性蛋白质，由胆固醇诱导，快速合成，以前被证明参与类固醇生成的急性调节，可能是通过促进胆固醇转移到线粒体内膜和细胞色素P450侧链裂解酶。用cAMP类似物二丁酰cAMP（dbcAMP）处理MA-10细胞导致星星蛋白水平的剂量和时间依赖性增加，在800 μ M dbcAMP和6小时内达到最大值。此外，用CRH处理MA-10细胞也导致星星蛋白合成的剂量依赖性增加，在1 μ M时观察到最大反应。与用dbcAMP观察到的略有不同，在刺激后4小时观察到对1 μ M CRH的最大反应。这些结果表明，在MA-10 Leydig肿瘤细胞中观察到的响应于CRH的类固醇产生的增加与先前观察到的通过cAMP第二信使途径起作用的营养激素刺激相似，并且它是由于星星蛋白合成增加而发生的。
We have previously demonstrated that corticotropin-releasing hormone (CRH) treatment of MA-10 mouse Leydig tumor cells results in a dose-dependent stimulation of progesterone production. In view of this observation we wished to determine the effects of CRH on the synthesis of the steroidogenic acute regulatory (StAR) protein in these cells. StAR is a steroidogenic tissue-specific, hormone-induced, rapidly synthesized protein previously shown to be involved in the acute regulation of steroidogenesis, probably by promoting the transfer of cholesterol to the inner mitochondrial membrane and the cytochrome P450 side-chain cleavage enzyme. Treatment of MA-10 cells with the cAMP analogue dibutyryl cAMP (dbcAMP) resulted in a dose-and time-dependent increase in the levels of StAR protein that reached a maximum at 800 mu M dbcAMP and within a time period of 6 h. Further, treatment of MA-10 cells with CRH also resulted in a dose-dependent increase in the synthesis of the StAR protein with a maximal response observed at 1 mu M. Slightly different from that observed with dbcAMP, the maximal response to 1 mu M CRH was seen at 4 h following stimulation. These results indicate that the observed increase in steroid production in response to CRH in MA-10 Leydig tumor cells is similar to that previously seen with trophic hormone stimulation acting through the cAMP second messenger pathway, and that it occurs as a result of an increase in the synthesis of the StAR protein.