Clark Adrian J L, Metherell Louise A
Centre for Endocrinology, the William Harvey Research Institute at Barts and the London, UK.
Nat Clin Pract Endocrinol Metab. 2006 May;2(5):282-90. doi: 10.1038/ncpendmet0165.
The action of the peptide hormone adrenocorticotropin (ACTH) to stimulate glucocorticoid production by the adrenal gland is an essential physiologic process, yet is dependent on a single unique genetic component--the ACTH receptor or melanocortin 2 receptor. Genetic defects that cause abnormalities in this receptor or in a protein required for its expression at the cell surface result in a potentially fatal disease (familial glucocorticoid deficiency). Overexpression of this receptor or inability to desensitize it is found in adrenal adenomas or hyperplasia associated with glucocorticoid overproduction (Cushing syndrome). These disorders are uncommon, but there are considerable data to show that the hypothalamo-pituitary-adrenal axis is overactive, or in some circumstances underactive, in more common situations including depressive illness and septic shock. The origin of these latter disturbances is undoubtedly complex and multifactorial, but there is good evidence that a component of this phenomenon is an altered responsiveness of the ACTH receptor to ACTH. Understanding the basis of ACTH responsiveness might, therefore, contribute to the understanding of disorders such as these and perhaps enable the hypothalamo-pituitary-adrenal axis to be manipulated beneficially in these circumstances.
肽类激素促肾上腺皮质激素（ACTH）刺激肾上腺产生糖皮质激素的作用是一个重要的生理过程，但它依赖于一个独特的基因成分——ACTH受体或黑皮质素2受体。导致该受体或其在细胞表面表达所需蛋白质异常的基因缺陷会引发一种潜在的致命疾病（家族性糖皮质激素缺乏症）。在与糖皮质激素过度分泌相关的肾上腺腺瘤或增生（库欣综合征）中，发现该受体过度表达或无法脱敏。这些疾病并不常见，但有大量数据表明，在包括抑郁症和脓毒性休克在内的更常见情况下，下丘脑 - 垂体 - 肾上腺轴会过度活跃，或在某些情况下活动不足。后一种紊乱的起源无疑是复杂且多因素的，但有充分证据表明，这种现象的一个因素是ACTH受体对ACTH的反应性改变。因此，了解ACTH反应性的基础可能有助于理解此类疾病，并且或许能够在这些情况下对下丘脑 - 垂体 - 肾上腺轴进行有益的调控。
