揭示微结节性肾上腺增生的分子基础。
Unraveling the molecular basis of micronodular adrenal hyperplasia.
作者信息
Horvath Anelia, Stratakis Constantine A
机构信息
Section on Endocrinology and Genetics, Program on Developmental Endocrinology & Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-1862, USA.
出版信息
Curr Opin Endocrinol Diabetes Obes. 2008 Jun;15(3):227-33. doi: 10.1097/MED.0b013e3282fe7416.
PURPOSE OF REVIEW
The present review discusses the molecular basis of micronodular adrenal hyperplasia. It focuses on the role of genetic defects in cyclic-AMP (cAMP) signaling-related molecules, namely PRKAR1A, GNAS, PDE11A, and PDE8B in the predisposition to tumor formation. This review also discusses the involvement of cAMP signaling and related pathways and their impact on the adrenocortical tumor formation.
RECENT FINDINGS
Molecular abnormalities in the phosphodiesterases family are the most recently discovered genetic abnormalities that predispose individuals to various adrenocortical tumors. In contrast to GNAS and PRKAR1A, defects in phosphodiesterases are associated more frequently with incomplete penetrance.
SUMMARY
Recent findings indicate the importance of cAMP signaling for normal adrenocortical functioning and the sensitivity of the adrenal gland to subtle alterations in cAMP levels. The identification of low-penetrance mutations in more than one phosphodiesterase in patients with adrenocortical hyperplasia is suggestive for a complementary role of the different phosphodiesterases in adrenal gland abnormalities and possible involvement of other members of this pathway in adrenocortical tumor defects.
综述目的
本综述探讨微结节性肾上腺增生的分子基础。重点关注环磷酸腺苷（cAMP）信号相关分子（即PRKAR1A、GNAS、PDE11A和PDE8B）中的基因缺陷在肿瘤形成易感性中的作用。本综述还讨论了cAMP信号及相关通路的参与情况及其对肾上腺皮质肿瘤形成的影响。
最新发现
磷酸二酯酶家族中的分子异常是最近发现的使个体易患各种肾上腺皮质肿瘤的基因异常。与GNAS和PRKAR1A不同，磷酸二酯酶缺陷更常与不完全外显率相关。
总结
最近的发现表明cAMP信号对正常肾上腺皮质功能的重要性以及肾上腺对cAMP水平细微变化的敏感性。在肾上腺皮质增生患者中，不止一种磷酸二酯酶存在低外显率突变，这提示不同磷酸二酯酶在肾上腺异常中具有互补作用，且该通路的其他成员可能参与肾上腺皮质肿瘤缺陷。
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