KCNJ5 mutations in aldosterone producing adenoma and relationship with adrenal cortex remodeling

Mol Cell Endocrinol. 2013 May 22;371(1-2):221-7. doi: 10.1016/j.mce.2013.01.018. Epub 2013 Jan 30.

Abstract

Somatic mutations of KCNJ5, coding for the potassium channel GIRK4, have recently been implicated in the formation of aldosterone producing adenoma (APA). While a causal link between KCNJ5 mutations, membrane depolarization and aldosterone production has been established, the precise mechanism by which these mutations promote cell proliferation and APA formation remains unclear. The aim of our study was to correlate KCNJ5 mutation status with morphological and functional characteristics of the adrenal cortex adjacent to APA. While GIRK4 was expressed in APA and in the zona glomerulosa of the adjacent cortex, significantly lower levels were detected in APA harboring a KCNJ5 mutation. There was no correlation between KCNJ5 mutation status and the morphological measures of adrenal cortex remodeling, including nodulation, vascularization and expression of CYP11B2. The cell composition of APA was not significantly different between groups. These results indicate that KCNJ5 mutations are not correlated with adrenal cortex remodeling in APA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Neoplasms / genetics*
  • Adrenal Cortex Neoplasms / metabolism
  • Adrenocortical Adenoma / genetics*
  • Adrenocortical Adenoma / metabolism
  • Aldosterone / biosynthesis
  • Aldosterone / metabolism*
  • Cell Proliferation
  • Cytochrome P-450 CYP11B2 / biosynthesis
  • Cytochrome P-450 CYP11B2 / genetics
  • Female
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels / genetics*
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels / metabolism
  • Humans
  • Male
  • Mutation
  • RNA, Messenger / biosynthesis
  • Zona Glomerulosa / metabolism*

Substances

  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • KCNJ5 protein, human
  • RNA, Messenger
  • Aldosterone
  • Cytochrome P-450 CYP11B2