Bourdeau Isabelle, Stratakis Constantine A
Unit on Genetics and Endocrinology, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892-1862, USA.
Ann N Y Acad Sci. 2002 Jun;968:240-55. doi: 10.1111/j.1749-6632.2002.tb04339.x.
The adrenal glands are a major source of steroid hormone biosynthesis. In normal physiology, the pituitary hormone corticotropin (ACTH) regulates the secretion of glucocorticoids via its G protein-coupled receptor (ACTHR), the product of the MC2R gene. Aldosterone is another major product of the adrenal gland; its regulation is controlled mainly by the renin-angiotensin system, although ACTH plays a role, too, especially under certain pathological conditions. The adrenal gland also secretes lesser amounts of androgens and intermediate metabolites of all these steroids. Unregulated secretion of any of these hormones can be caused by tumors, adrenocortical adenomas or carcinomas, and/or bilateral (or, rarely, unilateral) hyperplasia. Cortisol-producing hyperplasia of the adrenal glands is caused by two distinct syndromes, both of which have been directly or indirectly associated with protein kinase A signaling: (i) primary pigmented nodular adrenocortical disease (PPNAD) (a micronodular form of bilateral adrenal hyperplasia), either isolated (rarely) or in the context of Carney complex, is caused (in most cases) by mutations of the PRKAR1A gene; and (ii) ACTH-independent macronodular adrenal hyperplasia (AIMAH), or massive macronodular adrenal disease (MMAD), has been associated with aberrant (ectopic) expression, and presumably regulation, of various G protein-coupled receptors. AIMAH is a rare, sporadic condition affecting predominantly middle-aged men and women with an almost equal ratio (the latter in contrast to other forms of endogenous Cushing's syndrome). Some familial cases of AIMAH have also been described, and it appears that the pathophysiological phenomena underlying AIMAH may be present in the far more common, sporadic adrenocortical tumors and, perhaps, in the nodular growth detected in the adrenal glands of the elderly in the general population. Thus, the study of ectopic receptor expression and cAMP-dependent PKA activity in AIMAH may have wider implications for adrenal and, indeed, endocrine tumorigenesis.
肾上腺是类固醇激素生物合成的主要来源。在正常生理状态下，垂体激素促肾上腺皮质激素（ACTH）通过其G蛋白偶联受体（ACTHR，即MC2R基因的产物）调节糖皮质激素的分泌。醛固酮是肾上腺的另一种主要产物；其调节主要受肾素-血管紧张素系统控制，不过ACTH也发挥作用，尤其是在某些病理情况下。肾上腺还分泌少量雄激素以及所有这些类固醇的中间代谢产物。这些激素中任何一种的分泌失调都可能由肿瘤、肾上腺皮质腺瘤或癌，和/或双侧（或极少情况下为单侧）增生引起。肾上腺产生皮质醇的增生由两种不同的综合征引起，这两种综合征均直接或间接与蛋白激酶A信号传导相关：（i）原发性色素沉着性结节性肾上腺皮质病（PPNAD）（双侧肾上腺增生的微结节形式），可单独出现（罕见）或在卡尼综合征的背景下出现，（在大多数情况下）由PRKAR1A基因突变引起；（ii）ACTH非依赖性大结节性肾上腺增生（AIMAH），或巨大结节性肾上腺疾病（MMAD），与各种G蛋白偶联受体的异常（异位）表达以及推测的调节有关。AIMAH是一种罕见的散发性疾病，主要影响中年男性和女性，男女比例几乎相等（这与其他形式的内源性库欣综合征不同）。也有一些AIMAH的家族病例被描述，似乎AIMAH潜在的病理生理现象可能存在于更为常见的散发性肾上腺皮质肿瘤中，或许也存在于普通人群中老年患者肾上腺中检测到的结节性生长中。因此，对AIMAH中异位受体表达和cAMP依赖性PKA活性的研究可能对肾上腺乃至内分泌肿瘤发生具有更广泛的意义。
