Hales D B, Payne A H
Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor 48109-0278.
Endocrinology. 1989 May;124(5):2099-104. doi: 10.1210/endo-124-5-2099.
The regulation of cholesterol side-chain cleavage enzyme (P450scc) by glucocorticoids was investigated in mouse Leydig cell cultures. We recently demonstrated that P450scc is constitutively synthesized in Leydig cells and that the rate of P450scc synthesis is increased by chronic treatment of the cultures with 8-bromo-cAMP. We now report that glucocorticoids, specifically, decrease the constitutive and cAMP-induced synthesis of P450scc protein as well as the accumulation of P450scc mRNA. The treatment of cultures with as little as 10 nM dexamethasone resulted in a 50-60% decrease in the rate of synthesis of P450scc protein and mRNA content. The glucocorticoid-mediated decrease in P450scc synthesis was prevented when cultures were treated with the antiglucocorticoid RU-486. RU-486 alone had no effect on the rate of protein synthesis. The effect was specific for glucocorticoids; corticosterone (100 nM) or cortisol (100 nM) brought about a similar decrease as dexamethasone. Treatment of cultures with the progesterone agonist R5020 (100 nM), testosterone (2 microM), or estradiol (50 nM) had no effect on the rate of specific protein synthesis. The synthesis of iron sulfur protein reductase (ISP-reductase) and F1-ATPase were not affected by dexamethasone, indicating that the effect was specific for P450scc. The amount of P450scc mRNA was decreased 61% by dexamethasone and increased 144% by treatment with 8-bromo-cAMP. These data together with our previous finding on the negative regulation of P450(17 alpha) protein synthesis by testosterone suggest that the steroidogenic P450 enzymes in Leydig cells are negatively regulated by steroid hormones acting via their cognate receptors.
在小鼠睾丸间质细胞培养物中研究了糖皮质激素对胆固醇侧链裂解酶（P450scc）的调节作用。我们最近证明，P450scc在睾丸间质细胞中组成性合成，并且用8-溴-cAMP长期处理培养物可增加P450scc的合成速率。我们现在报告，糖皮质激素，具体而言，可降低P450scc蛋白的组成性和cAMP诱导的合成以及P450scc mRNA的积累。用低至10 nM地塞米松处理培养物会导致P450scc蛋白合成速率和mRNA含量降低50 - 60%。当用抗糖皮质激素RU - 486处理培养物时，可防止糖皮质激素介导的P450scc合成减少。单独使用RU - 486对蛋白质合成速率没有影响。该作用对糖皮质激素具有特异性；皮质酮（100 nM）或皮质醇（100 nM）产生与地塞米松类似的降低作用。用孕酮激动剂R5020（100 nM）、睾酮（2 μM）或雌二醇（50 nM）处理培养物对特异性蛋白质合成速率没有影响。地塞米松不影响铁硫蛋白还原酶（ISP - 还原酶）和F1 - ATP酶的合成，表明该作用对P450scc具有特异性。地塞米松使P450scc mRNA的量减少61%，而用8 - 溴 - cAMP处理则使其增加144%。这些数据连同我们之前关于睾酮对P450(17α)蛋白合成的负调节作用的发现表明，睾丸间质细胞中类固醇生成的P450酶受到通过其同源受体起作用的类固醇激素的负调节。
