Regulation of 3 beta-hydroxysteroid dehydrogenase in adrenocortical cells: effects of angiotensin-II and transforming growth factor beta.
Regulation of 3 beta-hydroxysteroid dehydrogenase in adrenocortical cells: effects of angiotensin-II and transforming growth factor beta.
复制标题
肾上腺皮质细胞中 3 β-羟基类固醇脱氢酶的调节：血管紧张素-II 和转化生长因子 β 的作用。
DOI：
10.1080/07435809109027202
复制
发表时间：
1991
影响因子：
2.1
通讯作者：
Mason,JI
中科院分区：
文献类型：
--
作者：
Rainey,WE;Naville,D;Mason,JI
肾上腺皮质细胞中最佳类固醇生成的维持主要取决于 ACTH 促进各种类固醇代谢酶合成的长期作用。在类固醇生成途径中，3β-羟基类固醇脱氢酶 (3β-HSD) 与 17α-羟化酶细胞色素 P450 (P-45017α) 的比率在确定肾上腺细胞释放的最终类固醇产物中起着关键作用。当考虑肾上腺区域和区域特异性类固醇的分泌时，这些酶的差异尤其重要。在本研究中，我们研究了 3βHSD 在酶活性、蛋白质水平以及编码该酶的特定 mRNA 变化方面的调节。原代培养八天后，发现牛肾上腺皮质 (BAC) 细胞通过增加皮质醇产量来对 ACTH 和 Bu2cAMP 做出反应。此外，3βHSD 活性、酶蛋白和 mRNA 水平因这两个因素而增加。活性的增加从 2 倍到 mRNA 的 5-7 倍不等。 ACTH 和 Bu2cAMP 也使 P-45017α 从对照细胞中几乎不可检测的水平大大增加。为了检查这些肾上腺类固醇生成酶差异调节的可能性，我们确定了血管紧张素 II (A-II) 和转化生长因子 β (TGFβ) 对这些酶水平的影响。这两个因素均将 ACTH 刺激的 P-45017α 酶和 mRNA 水平降低至对照细胞中观察到的接近不可检测的水平。此外，这些化合物还抑制 3βHSD 的 ACTH 诱导。虽然 TGFβ 的作用机制尚不清楚，但 A-II 可能是通过蛋白激酶 C 发挥作用。事实上，激活佛波酯 (TPA) 的蛋白激酶 C 模拟了 A-II 对 3βHSD 和 P45017α 的抑制作用。然而，重要的是要指出，A-II 和 TGFβ 对 P45017α 活性的影响似乎比 3βHSD 的作用更明显。这一观察结果可能与 3βHSD 与 P45017α 相比的相对稳定性有关。综合这些数据表明，虽然 A-II 和 TGFβ 各自降低类固醇代谢酶的水平，但观察到 P-45017α 蛋白和活性水平对这些因子的治疗更加敏感，存在差异调节。
The maintenance of optimal steroidogenesis in adrenocortical cells primarily depends on the chronic action of ACTH to promote the synthesis of the various steroid metabolizing enzymes. In the steroidogenic pathway, the ratio of 3β-hydroxysteroid dehydrogenase (3β-HSD) to 17α-hydroxylase cytochrome P450 (P-45017α) plays a key role in determining the final steroid products released by adrenal cells. The differences in these enzymes are particularly important when one considers the adrenal zones and the secretion of the zone-specific steroids. In the present study we have investigated the regulation of 3βHSD with regard to its enzyme activity, levels of protein and changes in specific mRNA encoding for this enzyme. Following eight days in primary culture, bovine adrenocortical (BAC) cells were found to respond to both ACTH and Bu2cAMP by increased cortisol production. In addition, 3βHSD activity, enzyme protein and mRNA levels were increased in response to both factors. The increases varied from 2-fold for activity to 5-7 fold for mRNA. ACTH and Bu2cAMP also greatly increased P-45017αfrom the near undetectable levels in control cells. In order to examine the possibility of differential regulation of these adrenal steroidogenic enzymes we determined the effects of angiotensin II (A-II) and transforming growth factor beta (TGFβ) on the levels of these enzymes. Both of these factors decreased the ACTH-stimulated levels of P-45017αenzyme and mRNA to near nondetectable levels observed within control cells. In addition, these compounds inhibited the ACTH induction of 3βHSD. While the mechanism of TGFβ action is not clear, A-II probably is acting through protein kinase C. Indeed the protein kinase C activating phorbol ester, TPA, mimicked the inhibitory effects of A-II on 3βHSD and P45017α. It is important to point out, however, that the effects of A-II and TGFβ on P45017αactivity appeared more pronounced than their action of 3βHSD. This observation may relate to the relative stability of 3βHSD as compared to P45017α. Taken together these data indicate that, while A-II and TGFβ each decrease the levels of steroid-metabolizing enzymes, a differential regulation is observed in that P-45017αprotein and activity levels are much more sensitive to treatment with these factors.