Format

Send to

Choose Destination
See comment in PubMed Commons below
Mol Cell Endocrinol. 2009 Mar 5;300(1-2):152-7. doi: 10.1016/j.mce.2008.11.010. Epub 2008 Nov 21.

New genes and/or molecular pathways associated with adrenal hyperplasias and related adrenocortical tumors.

Author information

1
Section on Endocrinology & Genetics, Program on Developmental Endocrinology & Genetics (PDEGEN), Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), Bethesda, MD 20892, USA. stratakc@mail.nih.gov

Abstract

Over the course of the last 10 years, we have studied the genetic and molecular mechanisms leading to disorders that affect the adrenal cortex, with emphasis on those that are developmental, hereditary and associated with adrenal hypoplasia or hyperplasia, multiple tumors and abnormalities in other endocrine glands. On the basis of this work, we propose an hypothesis on how adrenocortical tumors form and the importance of the cyclic AMP-dependent signaling pathway in this process. The regulatory subunit type 1-alpha (RIalpha) of protein kinase A (PKA) (the PRKAR1A gene) is mutated in most patients with Carney complex and primary pigmented nodular adrenocortical disease (PPNAD). Phosphodiesterase-11A (the PDE11A gene) and -8B (the PDE8B gene) mutations were found in patients with isolated adrenal hyperplasia and Cushing syndrome, as well in patients with PPNAD. PKA effects on tumor suppression and/or development and the cell cycle are becoming clear: PKA and/or cAMP act as a coordinator of growth and proliferation in the adrenal cortex. Mouse models in which the respective genes have been knocked out see m to support this notion. Genome-wide searches for other genes responsible for adrenal tumors and related diseases are ongoing; recent evidece of the involvement of the mitochondrial oxidation pathway in adrenocortical tumorigenesis is derived from our study of rare associations such as those of disorders predisposing to adrenomedullary and related tumors (Carney triad, the dyad of paragangliomas and gastric stromal sarcomas or Carney-Stratakis syndrome, hereditary leiomyomatosis and renal cancer syndrome) which appear to be associated with adrenocortical lesions.

PMID:
19063937
PMCID:
PMC2668239
DOI:
10.1016/j.mce.2008.11.010
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center