HORMONAL AND DEVELOPMENTAL REGULATION OF THE STEROIDOGENIC ACUTE REGULATORY PROTEIN
HORMONAL AND DEVELOPMENTAL REGULATION OF THE STEROIDOGENIC ACUTE REGULATORY PROTEIN
复制标题
DOI：
10.1210/me.9.10.1346
复制
发表时间：
1995-10-01
影响因子：
--
通讯作者：
STOCCO, DM
中科院分区：
文献类型：
--
作者：
CLARK, BJ;SOO, SC;STOCCO, DM
营养激素对类固醇形成的急性调节中一个关键的事件是胆固醇进入线粒体，在那里它被胆固醇侧链切割酶转化为孕烯醇酮。尽管关于激素刺激下这种急性反应的确切机制存在相当大的争议，但最近的研究表明，类固醇急性调节（StAR）蛋白，一种激素诱导的30千顿线粒体蛋白，起着至关重要的作用。我们现在通过在MA-10小鼠间质肿瘤细胞中建立StAR表达水平与激素刺激下类固醇生成之间的时间关系来扩展这些研究。这些数据表明，营养激素在类固醇激素急性产生的时间框架内调节StAR mRNA和蛋白质，并提供了第一个证据，表明类固醇细胞对激素作用的功能反应中StAR转录和/或mRNA稳定性的变化。此外，对胚胎和成年小鼠StAR表达的原位杂交分析表明，StAR表达与体内产生类固醇激素的能力之间存在精确的时空关系，这些实验大大加强了StAR是急性诱导类固醇生成的关键介质的证据，并为营养激素激活类固醇生成细胞的机制提供了新的见解。
A crucial event in the acute regulation of steroidogenesis by trophic hormones is the delivery of cholesterol into the mitochondria where it is converted to pregnenolone by the cholesterol side chain cleavage enzyme. Although considerable controversy exists regarding the exact mechanisms that underlie this acute response to hormone stimulation, recent studies suggest that the Steroidogenic Acute Regulatory (StAR) protein, a hormone-induced 30-kilodalton mitochondrial protein, plays an essential role, We now extend these studies by establishing in MA-10 mouse Leydig tumor cells a temporal relationship between levels of StAR expression and steroidogenesis in response to hormone stimulation. These data indicate that trophic hormones regulate StAR mRNA and protein within a time frame concomitant with the acute production of steroid hormones and provide the first evidence implicating changes in StAR transcription and/or mRNA stability in the functional response of steroidogenic cells to hormone action. In addition, in situ hybridization analyses of StAR expression in embryonic and adult mice demonstrated a precise spatial and temporal relationship in vivo between StAR expression and the capacity to produce steroid hormones, These experiments strengthen considerably the evidence that StAR is the key mediator of the acute induction of steroidogenesis and provide new insights into the mechanisms by which trophic hormones activate steroidogenesis in steroidogenic cells.