Phosphodiesterases and Adrenal Cushing in Mice and Humans

E. Szarek; C. A. Stratakis

doi:10.1055/s-0034-1389916

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2014; 46(12): 863-868
DOI: 10.1055/s-0034-1389916

Review

Phosphodiesterases and Adrenal Cushing in Mice and Humans

Authors

E. Szarek

¹Section of Endocrinology and Genetics, Program on Developmental Endocrinology Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA
C. A. Stratakis

¹Section of Endocrinology and Genetics, Program on Developmental Endocrinology Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA

Abstract

The majority of benign adrenal cortex lesions leading to Cushing syndrome are associated to one or another abnormality of the cAMP/cGMP-phosphodiesterase signaling pathway. Phosphodiesterases (PDEs) are key regulatory enzymes of intracellular cAMP/cGMP levels. These second messengers play important regulatory roles in controlling steroidogenesis in the adrenal. Disruption of PDEs has been associated with a number of adrenal diseases. Specifically, genetic mutations have been associated with benign adrenal lesions, leading to Cushing syndrome and/or related adrenal hyperplasias. A Genome Wide Association study, in 2006, led to the identification of mutations in 2 PDE genes: PDE8B and PDE11A; mutations in these 2 genes modulate steroidogenesis. Further human studies have identified PDE2 as also directly regulating steroidogenesis. PDE2 decreases aldosterone production. This review focuses on the most recent knowledge we have gained on PDEs and their association with adrenal steroidogenesis and altered function, through analysis of patient cohorts and what we have learned from mouse studies.

Key words

PDE2A - PDE8B - PDE11A - Cushing syndrome - cAMP - bilateral adrenal hyperplasia

Full Text

References

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