Clark B J, Pezzi V, Stocco D M, Rainey W E
Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock 79430, USA.
Mol Cell Endocrinol. 1995 Dec 29;115(2):215-19. doi: 10.1016/0303-7207(95)03683-0.
Adrenal steroid hormone biosynthesis can be activated by the protein kinase A pathway by ACTH, the protein kinase C pathway by angiotensin II (AII), or by increasing intracellular Ca2+ levels by AII or K+. Although their mechanisms of action are not known, each of these pathways is dependent upon the de novo synthesis of a protein that is required for the acute production of steroids. We have recently proposed the steroidogenic acute regulatory (StAR) protein as this required protein, therefore, we examined the effect of different agonists on StAR's expression in H295R human adrenocortical carcinoma cells. (Bu)2cAMP, AII, K+, BAYK8644 (a calcium channel agonist) and TPA are all shown to induce StAR. Aldosterone synthesis was stimulated by all the agonists with the exception of TPA, indicating that AII-stimulated steroid production is mediated by increases in intracellular calcium. Thus, these data suggest that regulation of StAR expression may represent a common mechanism for divergent pathways to acutely control adrenal steroidogenesis.
肾上腺类固醇激素的生物合成可通过促肾上腺皮质激素激活蛋白激酶A途径、血管紧张素II（AII）激活蛋白激酶C途径，或通过AII或钾离子增加细胞内钙离子水平来实现。尽管它们的作用机制尚不清楚，但这些途径中的每一条都依赖于一种蛋白质的从头合成，而这种蛋白质是类固醇急性生成所必需的。最近我们提出类固醇生成急性调节（StAR）蛋白就是这种必需的蛋白质，因此，我们研究了不同激动剂对H295R人肾上腺皮质癌细胞中StAR表达的影响。双丁酰环磷腺苷（Bu）2cAMP、AII、钾离子、BAYK8644（一种钙通道激动剂）和佛波酯（TPA）均显示可诱导StAR。除TPA外，所有激动剂均刺激醛固酮合成，这表明AII刺激的类固醇生成是由细胞内钙离子增加介导的。因此，这些数据表明，StAR表达的调节可能是不同途径急性控制肾上腺类固醇生成的共同机制。
