ERK1/2 MAPKs and Wnt Signaling Pathways are Independently Involved in Adipocytokine-Mediated Aldosterone Secretion

K. Vleugels; S. Schinner; D. Krause; H. Morawietz; S. R. Bornstein; M. Ehrhart-Bornstein; A. W. Krug

doi:10.1055/s-0031-1284367

Experimental and Clinical Endocrinology & Diabetes, Inhaltsverzeichnis

Exp Clin Endocrinol Diabetes 2011; 119(10): 644-648
DOI: 10.1055/s-0031-1284367

Article

ERK1/2 MAPKs and Wnt Signaling Pathways are Independently Involved in Adipocytokine-Mediated Aldosterone Secretion

K. Vleugels

¹Medical Clinic III, University Hospital Carl Gustav Carus, Dresden, Germany

,

S. Schinner

²Department of Endocrinology, Diabetes and Rheumatology, University Hospital Düsseldorf, Düsseldorf, Germany

,

D. Krause

²Department of Endocrinology, Diabetes and Rheumatology, University Hospital Düsseldorf, Düsseldorf, Germany

,

H. Morawietz

¹Medical Clinic III, University Hospital Carl Gustav Carus, Dresden, Germany

,

S. R. Bornstein

¹Medical Clinic III, University Hospital Carl Gustav Carus, Dresden, Germany

,

M. Ehrhart-Bornstein

³Brigham and Women’s Hospital, Harvard Medical School, Division of Endocrinology, Diabetes, and Hypertension, Boston, United States

,

A. W. Krug

³Brigham and Women’s Hospital, Harvard Medical School, Division of Endocrinology, Diabetes, and Hypertension, Boston, United States

› Institutsangaben

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 adrenocortical 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.

Key words

obesity - adipocytokines - hypertension - aldosterone - adrenal cortex - ERK1/2 MAPK - Wnt

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Referenzen

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