title: ERK1/2 MAPKs and Wnt signaling pathways are independently involved in adipocytokine-mediated aldosterone secretion.
abstract: 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.
authors.affiliation: Medical Clinic III, University Hospital Carl Gustav Carus, Dresden, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Vleugels
authors.forename: S
authors.initials: S
authors.lastname: Schinner
authors.forename: D
authors.initials: D
authors.lastname: Krause
authors.forename: H
authors.initials: H
authors.lastname: Morawietz
authors.forename: S R
authors.initials: SR
authors.lastname: Bornstein
authors.forename: M
authors.initials: M
authors.lastname: Ehrhart-Bornstein
authors.forename: A W
authors.initials: AW
authors.lastname: Krug
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D054392:Adipokines / Q000378:metabolism*; D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism*; D000450:Aldosterone / Q000378:metabolism*; D002450:Cell Communication / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D005260:Female; D017930:Genes, Reporter / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D050505:Mutant Proteins / Q000378:metabolism; D050177:Overweight / Q000378:metabolism* / Q000473:pathology; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D054339:Steroidogenic Factor 1 / Q000378:metabolism; D050151:Subcutaneous Fat / Q000378:metabolism / Q000473:pathology; D060449:Wnt Signaling Pathway / Q000187:drug effects; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D054392:Adipokines; C495270:CTNNB1 protein, human; D050505:Mutant Proteins; C515057:NR5A1 protein, human; D010750:Phosphoproteins; D011994:Recombinant Proteins; D054339:Steroidogenic Factor 1; D051176:beta Catenin; D000098682:Steroidogenic Acute Regulatory Protein; D000450:Aldosterone