Unraveling the molecular basis of micronodular adrenal hyperplasia.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Horvath
Anelia
A
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.
Stratakis
Constantine A
CA
D000306:Adrenal Cortex Neoplasms / Q000145:classification / Q000235:genetics* / Q000503:physiopathology*; D000311:Adrenal Glands / Q000503:physiopathology; D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D006965:Hyperplasia / Q000235:genetics* / Q000503:physiopathology*; D015290:Second Messenger Systems