Nishikawa T, Omura M, Suematsu S
Department of Medicine, Yokohama Rosai Hospital, Yokohama City, Japan.
Endocr J. 1997 Dec;44(6):895-8. doi: 10.1507/endocrj.44.895.
Steroidogenic acute regulatory (StAR) protein plays a crucial role in the regulation of cholesterol transport from the outer mitochondrial membrane to the inner membrane, where P450scc participates in a rate-limiting step of adrenal steroidogenesis. We have already reported that both of cAMP- and protein kinase C-dependent processes may play a crucial role in the regulation of expression of StAR protein when bovine fasciculata cells are stimulated with ACTH. In the present study, ACTH increased cytosolic calcium movement and activated expression of StAR protein, resulting in enhancing cortisol production by bovine adrenal fasciculata cells. The role of the calcium/calmodulin-dependent protein kinase process in the regulation of expression of the StAR protein by ACTH was studied. The activating effects of ACTH on the StAR protein and cortisol production were inhibited by pretreatment with KN-93, a specific inhibitor of calcium/calmodulin-dependent protein kinase II. These findings suggest that ACTH can enhance expression of the StAR protein as well as cortisol synthesis in bovine adrenal fasciculata cells, in part via a calcium/calmodulin-dependent protein kinase process.
类固醇生成急性调节(StAR)蛋白在胆固醇从线粒体外膜转运至内膜的过程中发挥着关键作用,在此过程中,细胞色素P450侧链裂解酶(P450scc)参与肾上腺类固醇生成的限速步骤。我们已经报道,当用促肾上腺皮质激素(ACTH)刺激牛束状带细胞时,cAMP依赖性和蛋白激酶C依赖性过程可能在StAR蛋白表达的调节中起关键作用。在本研究中,ACTH增加了胞质钙转运并激活了StAR蛋白的表达,从而导致牛肾上腺束状带细胞皮质醇生成增加。研究了钙/钙调蛋白依赖性蛋白激酶过程在ACTH对StAR蛋白表达调节中的作用。用钙/钙调蛋白依赖性蛋白激酶II的特异性抑制剂KN-93预处理可抑制ACTH对StAR蛋白和皮质醇生成的激活作用。这些发现表明,ACTH可以增强牛肾上腺束状带细胞中StAR蛋白的表达以及皮质醇的合成,部分是通过钙/钙调蛋白依赖性蛋白激酶过程实现的。