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肾上腺髓质中类固醇对单胺氧化酶活性的调节。

Steroid regulation of monoamine oxidase activity in the adrenal medulla.

作者信息

Youdim M B, Banerjee D K, Kelner K, Offutt L, Pollard H B

机构信息

Laboratory of Cell Biology and Genetics, National Institute of Diabetes, Digestive, and Kidney Diseases, Bethesda, Maryland 20892.

出版信息

FASEB J. 1989 Apr;3(6):1753-9. doi: 10.1096/fasebj.3.6.2495232.

Abstract

Administration of different steroid hormones in vivo has distinct and specific effects on the MAO activity of the adrenal medulla. In an effort to reconstitute these effects in defined cells, we have isolated endothelial cells and chromaffin cells from the bovine adrenal medulla and tested each cell type for sensitivity to these steroids. As in the intact animal, we found that endothelial cell MAO activity was stimulated 1.5- 2.5-fold by 10 microM progesterone, hydrocortisone, and dexamethasone, inhibited by ca. 50% by 17-alpha-estradiol, but unaffected by testosterone. The type of MAO in the endothelial cells was found to be exclusively of the A type. The chromaffin cells had MAO B exclusively and were inert to treatment with dexamethasone. The mode of action of the various steroids on MAO A activity in endothelial cells seemed to be that of affecting the number of MAO molecules, as binding of [3H]pargyline, an MAO inhibitor, changed in proportion to changes in enzyme activity. Consistently, the kinetic parameters for MAO A showed changes in Vmax but not Km under all conditions. The specificity of steroid action on MAO A activity was also supported by the fact that steroid-induced changes in total cell division ([14C]thymidine incorporation) and total protein synthesis ([14C]leucine incorporation) were seen after changes in MAO A. We conclude that the differential effects of steroids on MAO activity in the intact adrenal medulla can be reproduced in cultured adrenal medullary endothelial cells but not in chromaffin cells. Therefore we suggest that the action of these steroid hormones on the intact adrenal medulla may be restricted to the endothelial cell component of this tissue.

摘要

在体内给予不同的类固醇激素对肾上腺髓质的单胺氧化酶(MAO)活性有独特而特定的影响。为了在特定细胞中重现这些效应,我们从牛肾上腺髓质中分离出内皮细胞和嗜铬细胞,并测试了每种细胞类型对这些类固醇的敏感性。与完整动物一样,我们发现10微摩尔的孕酮、氢化可的松和地塞米松可使内皮细胞MAO活性提高1.5至2.5倍,17-α-雌二醇可使其活性降低约50%,而睾酮对其无影响。发现内皮细胞中的MAO类型完全是A型。嗜铬细胞仅含有MAO B,对地塞米松处理无反应。各种类固醇对内皮细胞中MAO A活性的作用方式似乎是影响MAO分子的数量,因为MAO抑制剂[3H]帕吉林的结合与酶活性的变化成比例。一致地,在所有条件下,MAO A的动力学参数显示Vmax发生变化,但Km不变。MAO A活性的类固醇作用特异性还得到以下事实的支持:在MAO A发生变化后,观察到类固醇诱导的总细胞分裂([14C]胸腺嘧啶掺入)和总蛋白质合成([14C]亮氨酸掺入)的变化。我们得出结论,类固醇对完整肾上腺髓质中MAO活性的差异效应可以在培养的肾上腺髓质内皮细胞中重现,但在嗜铬细胞中则不能。因此,我们认为这些类固醇激素对完整肾上腺髓质的作用可能仅限于该组织的内皮细胞成分。

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