ERK1/2 MAPKs and Wnt signaling pathways are independently involved in adipocytokine-mediated aldosterone secretion

• Published in: Experimental and clinical endocrinology & diabetes Vol. 119; no. 10; p. 644
• Main Authors: Vleugels, K, Schinner, S, Krause, D, Morawietz, H, Bornstein, S R, Ehrhart-Bornstein, M, Krug, A W
• Format: Journal Article
• Language: English
• Published: Germany 01.11.2011
• Subjects: Adipocytes - secretion; Adipokines - secretion; Adrenal Cortex - drug effects; Adrenal Cortex - metabolism; Adrenal Cortex - secretion; Aldosterone - secretion; beta Catenin - genetics; beta Catenin - metabolism; Cell Communication - drug effects; Cell Line; Cells, Cultured; Female; Genes, Reporter - drug effects; Humans; MAP Kinase Signaling System - drug effects; Mutant Proteins - metabolism; Overweight - metabolism; Overweight - pathology; Phosphoproteins - genetics; Phosphoproteins - metabolism; Phosphorylation - drug effects; Promoter Regions, Genetic - drug effects; Protein Processing, Post-Translational - drug effects; Recombinant Proteins - antagonists & inhibitors; Recombinant Proteins - metabolism; Steroidogenic Factor 1 - metabolism; Subcutaneous Fat - pathology; Subcutaneous Fat - secretion; Wnt Signaling Pathway - drug effects
• ISSN: 1439-3646
• DOI: 10.1055/s-0031-1284367

Obesity is one major risk factor for the development of arterial hypertension, and the development of obesity-related hypertension has been associated with increased plasma aldosterone levels. Our previous work shows a direct stimulatory effect of adipokines on aldosterone secretion from human adrenocortical cells, mediated via ERK1/2-dependent upregulation of steroid acute regulatory protein (StAR) activity. Recent evidence also indicates the involvement of the Wnt-signaling pathway in fat cell-mediated aldosterone secretion. Wnt-signaling molecules are secreted by adipocytes and regulate the activity of SF-1, a key transcription factor in adrenal steroidogenesis. The goal of this study was to investigate the cellular mechanisms of adipocyte-induced aldosterone secretion in detail, and to evaluate effects and possible interactions of the ERK1/2 MAPK- and the Wnt-signaling pathways on adipocyte-induced adreno-cortical aldosterone secretion. Our results show that, similar to adipocyte-conditioned medium (ACM), β-catenin, which is an intracellular mediator of canonical Wnt-signaling, induced StAR promotor activity in human NCI-H295R adrenocortical cells, and ACM-induced StAR promotor activity depended on intact SF-1 binding sites. Wnt antagonist sFRP-1 inhibited adipokine-mediated StAR activity, but did not affect ERK1/2 MAPK activation. Accordingly, Wnt did not stimulate ERK1/2 phosphorylation in adrenocortical cells, indicating that ERK1/2 MAPK and Wnt signaling pathways are independently involved in adipocyte-mediated aldosterone secretion.