Severe hyperaldosteronism in neonatal Task3 potassium channel knockout mice is associated with activation of the intraadrenal renin-angiotensin system

Endocrinology. 2013 Aug;154(8):2712-22. doi: 10.1210/en.2013-1101. Epub 2013 May 22.

Abstract

Task3 K(+) channels are highly expressed in the adrenal cortex and contribute to the angiotensin II and K(+) sensitivity of aldosterone-producing glomerulosa cells. Adult Task3(-/-) mice display a partially autonomous aldosterone secretion, subclinical hyperaldosteronism, and salt-sensitive hypertension. Here, we investigated the age dependence of the adrenal phenotype of Task3(-/-) mice. Compared with adults, newborn Task3(-/-) mice displayed a severe adrenal phenotype with strongly increased plasma levels of aldosterone, corticosterone, and progesterone. This adrenocortical dysfunction was accompanied by a modified gene expression profile. The most strongly up-regulated gene was the protease renin. Real-time PCR corroborated the strong increase in adrenal renin expression, and immunofluorescence revealed renin-expressing cells in the zona fasciculata. Together with additional factors, activation of the local adrenal renin system is probably causative for the severely disturbed steroid hormone secretion of neonatal Task3(-/-) mice. The changes in gene expression patterns of neonatal Task3(-/-) mice could also be relevant for other forms of hyperaldosteronism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Glands / metabolism*
  • Aldosterone / blood
  • Aldosterone / metabolism
  • Animals
  • Animals, Newborn
  • Corticosterone / blood
  • Corticosterone / metabolism
  • Cytochrome P-450 CYP11B2 / genetics
  • Cytochrome P-450 CYP11B2 / metabolism
  • Female
  • Fluorescent Antibody Technique
  • Gene Expression Profiling
  • Hyperaldosteronism / blood
  • Hyperaldosteronism / genetics*
  • Hyperaldosteronism / metabolism
  • Kidney / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oligonucleotide Array Sequence Analysis
  • Potassium Channels / deficiency
  • Potassium Channels / genetics*
  • Progesterone / blood
  • Progesterone / metabolism
  • Renin / blood
  • Renin / genetics
  • Renin / metabolism
  • Renin-Angiotensin System / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Zona Fasciculata / metabolism

Substances

  • Potassium Channels
  • TASK3 protein, mouse
  • Aldosterone
  • Progesterone
  • Cytochrome P-450 CYP11B2
  • Renin
  • Corticosterone