Exp Clin Endocrinol Diabetes 2007; 115 - P01_059
DOI: 10.1055/s-2007-972315

Adipocyte-induced ERK1/2-mediated StAR activation enhances aldosterone secretion and sensitizes human adrenocortical cells to AngII

K Vleugels 1, S Schinner 2, U Buro 1, S Sperber 1, SR Bornstein 1, M Ehrhart-Bornstein 1, AW Krug 1
  • 1University Hospital Carl Gustav Carus, Medical Clinic III, Dresden, Germany
  • 2University Hospital Düsseldorf, Department of Endocrinology, Düsseldorf, Germany

Obesity is one of the most important risk factors for the development of arterial hypertension. Aldosterone plasma levels are frequently elevated in obese patients. Aldosterone enhances renal sodium and water retention, thus increasing blood pressure. Our previous work suggests a direct stimulatory effect of adipocyte secretory products on adrenal aldosterone secretion, providing a possible new link between adipose tissue function and high blood pressure. In addition to this direct mineralocorticoid stimulating activity fat cells might also sensitize adrenocortical cells to other stimuli, such as angiotensin II (AngII). Therefore, one aim of this study was to investigate whether adipokines induce sensitization of adrenocortical cells towards AngII as a further link between overweight and increased aldosterone secretion. In a next step we aimed at elucidating the intracellular signalling mechanisms involved in adipocyte-induced aldosterone production. AngII-mediated aldosterone secretion was dramatically increased by preincubation of adrenocortical cells (H295R cells) with adipocyte conditioned media (ACM).

Steroid acute regulatory protein (StAR) gene activity was enhanced after 3h incubation of H295R cells with ACM as indicated by real-time PCR and a StAR luciferase reporter assay. StAR protein expression was elevated after 24h incubation as shown by Western Blot analysis. Upregulation of StAR was accompanied by ERK1/2 MAPK activation in a time-and dose-dependent way and nuclear translocation of the kinases as demonstrated by Western Blot, ELISA and immunocytochemistry. Importantly, inhibition of MAPK by UO126 inhibited StAR gene activity as well as aldosterone secretion, indicating a major role for ERK1/2.

Taken together, our data indicate that adipocyte-mediated aldosterone secretion and sensitization of adrenocortical cells to AngII is mediated via ERK1/2-dependent upregulation of StAR activity in human adrenocortical cells.