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肾上腺类固醇激素的生物合成

Author
Lynnette K Nieman, MD
Section Editor
André Lacroix, MD
Deputy Editor
Kathryn A Martin, MD
Translators
邵加庆, 主任医师

引言

促肾上腺皮质激素(adrenocorticotropic hormone, ACTH)对肾上腺皮质的主要作用是，通过增加皮质醇的合成从而增加其分泌。在肾上腺内，皮质醇的储存量极小[1]。主要的几种肾上腺类固醇激素是在肾上腺皮质的不同区域合成的：糖皮质激素(尤其是皮质醇)、雄激素和雌激素是在束状带和网状带合成的，醛固酮是在球状带合成的。认识这些途径，是理解不同形式的先天性肾上腺皮质增生症(congenital adrenal hyperplasia, CAH)与孤立性醛固酮减少症的基础，在这两类疾病中，参与合成肾上腺类固醇激素的酶的功能存在缺陷。

本文将总结肾上腺类固醇激素生成所涉及的步骤。肾上腺类固醇激素的代谢详见其他专题。 (参见“肾上腺类固醇的代谢”)

ACTH作用机制

ACTH通过与细胞表面特定受体[黑皮质素受体2(melanocortin receptor-2, MC2R)]结合来发挥作用[2]。ACTH可上调这些受体的表达，从而导致在进一步ACTH刺激下类固醇生成增加[3]。

MC2R对ACTH无反应而未能激活时，可导致家族性糖皮质激素缺乏症(familial glucocorticoid deficiency, FGD)，这是一种罕见的常染色体隐形遗传病，其特征为严重的皮质醇缺乏伴ACTH血浆高水平和正常的盐皮质激素水平(参见“肾上腺皮质功能减退症的罕见病因”，关于‘家族性糖皮质激素缺乏症’一节)。1型FGD的原因在于MC2R基因突变导致受体功能的实际性丢失，FGD病例中1型占比可多达25%[4]。黑皮质素受体辅助蛋白(melanocortin receptor accessory protein, MRAP)和其旁系同源蛋白MRAP2都是小型单次跨膜蛋白，MRAP是MC2R/ACTH受体功能表达的关键辅助因子。临床观察发现，20%的FGD是由MRAP失活突变所致，这一观察结果突出了MRAP在肾上腺生理学中的重要性[5]。

ACTH与其受体结合，激活腺苷酸环化酶，从而增加环磷酸腺苷(cAMP)的生成，进一步刺激cAMP依赖性蛋白激酶(蛋白激酶A)，以及一系列蛋白的磷酸化。

             

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Literature review current through: 2017-06 . | This topic last updated: 2015-10-13.
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