title: Severe hyperaldosteronism in neonatal Task3 potassium channel knockout mice is associated with activation of the intraadrenal renin-angiotensin system.
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.
authors.affiliation: Department of Medical Cell Biology, University of Regensburg, 93053 Regensburg, Germany. sascha.bandulik@ur.de
authors.forename: Sascha
authors.initials: S
authors.lastname: Bandulik
authors.forename: Philipp
authors.initials: P
authors.lastname: Tauber
authors.forename: David
authors.initials: D
authors.lastname: Penton
authors.forename: Frank
authors.initials: F
authors.lastname: Schweda
authors.forename: Ines
authors.initials: I
authors.lastname: Tegtmeier
authors.forename: Christina
authors.initials: C
authors.lastname: Sterner
authors.forename: Enzo
authors.initials: E
authors.lastname: Lalli
authors.forename: Florian
authors.initials: F
authors.lastname: Lesage
authors.forename: Michaela
authors.initials: M
authors.lastname: Hartmann
authors.forename: Jacques
authors.initials: J
authors.lastname: Barhanin
authors.forename: Richard
authors.initials: R
authors.lastname: Warth
mesh_terms: D000311:Adrenal Glands / Q000378:metabolism*; D000450:Aldosterone / Q000097:blood / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D003345:Corticosterone / Q000097:blood / Q000378:metabolism; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D006929:Hyperaldosteronism / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D015221:Potassium Channels / Q000172:deficiency / Q000235:genetics*; D011374:Progesterone / Q000097:blood / Q000378:metabolism; D012083:Renin / Q000097:blood / Q000235:genetics / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015383:Zona Fasciculata / Q000378:metabolism
chemical_list: D015221:Potassium Channels; C511784:TASK3 protein, mouse; D000450:Aldosterone; D011374:Progesterone; D019405:Cytochrome P-450 CYP11B2; D012083:Renin; D003345:Corticosterone