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Vohra, T.* ; Kemter, E.* ; Sun, N. ; Dobenecker, B.* ; Hinrichs, A.* ; Burrello, J.* ; Gomez-Sanchez, E.P.* ; Gomez-Sanchez, C.E.* ; Wang, J. ; Kinker, I.S.* ; Teupser, D.* ; Fischer, K.* ; Schnieke, A.* ; Peitzsch, M.* ; Eisenhofer, G.* ; Walch, A.K. ; Reincke, M.* ; Wolf, E.* ; Williams, T.A.*

Effect of dietary sodium modulation on pig adrenal steroidogenesis and transcriptome profiles.

Hypertension 76, 1769-1777 (2020)
Primary aldosteronism is a frequent form of endocrine hypertension caused by aldosterone overproduction from the adrenal cortex. Regulation of aldosterone biosynthesis has been studied in rodents despite differences in adrenal physiology with humans. We, therefore, investigated pig adrenal steroidogenesis, morphology, and transcriptome profiles of the zona glomerulosa (zG) and zona fasciculata in response to activation of the renin-angiotensin-aldosterone system by dietary sodium restriction. Six-week-old pigs were fed a low- or high-sodium diet for 14 days (3 pigs per group, 0.4 g sodium/kg feed versus 6.8 g sodium/kg). Plasma aldosterone concentrations displayed a 43-fold increase (P=0.011) after 14 days of sodium restriction (day 14 versus day 0). Low dietary sodium caused a 2-fold increase in thickness of the zG (P<0.001) and an almost 3-fold upregulation of CYP11B (P<0.05) compared with high dietary sodium. Strong immunostaining of the KCNJ5 (G protein-activated inward rectifier potassium channel 4), which is frequently mutated in primary aldosteronism, was demonstrated in the zG. mRNA sequencing transcriptome analysis identified significantly altered expression of genes modulated by the renin-angiotensin-aldosterone system in the zG (n=1172) and zona fasciculata (n=280). These genes included many with a known role in the regulation of aldosterone synthesis and adrenal function. The most highly enriched biological pathways in the zG were related to cholesterol biosynthesis, steroid metabolism, cell cycle, and potassium channels. This study provides mechanistic insights into the physiology and pathophysiology of aldosterone production in a species closely related to humans and shows the suitability of pigs as a translational animal model for human adrenal steroidogenesis.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Adrenal Cortex ; Aldosterone ; Hydrocortisone ; Hyperaldosteronism ; Hypertension ; Models ; Animal ; Sodium; Angiotensin-ii; Aldosterone Production; Adrenocortical Carcinoma; Potassium Channel; Zona Glomerulosa; Regulatory Genes; Kcnj5 Mutations; Binding Protein; 18-oxocortisol; Expression
ISSN (print) / ISBN 0194-911x
e-ISSN 1524-4563
Journal Hypertension
Quellenangaben Volume: 76, Issue: 6, Pages: 1769-1777 Article Number: , Supplement: ,
Publisher Lippincott Williams & Wilkins
Publishing Place Two Commerce Sq, 2001 Market St, Philadelphia, Pa 19103 Usa
Reviewing status Peer reviewed
Grants Deutsche Forschungsgemeinschaft
National Institute of General Medical Sciences from Department of Veterans Affairs
National Heart, Lung, and Blood Institute
Deutsche Forschungsgemeinschaft (German Research Foundation)
European Research Council under European Union