One important risk factor for the development of arterial hypertension is abdominal obesity. Aldosterone, secreted by adrenocortical cells, promotes sodium and water retention and by that regulates blood pressure homeostasis. Increased serum aldosterone levels have been linked to the development of obesity hypertension. Therefore, identifying the link between obesity and increased aldosterone secretion is of high importance for the management of obesity hypertension.
Isolated human adipocytes secrete factors that stimulate steroid secretion from human adrenocortical cells with a predominant effect on aldosterone secretion.
We could show that adipocyte-mediated aldosterone secretion and sensitization of human adrenocortical cells to angiotensin II (AngII) is mediated via ERK1/2-MAPKs-dependent upregulation of steroidogenic acute regulatory (StAR) protein activity. Inhibition of MAPKs by UO126 almost completely abolished adipocyte-induced steroidogenesis. Recent evidence also indicates the involvement of the Wnt-signalling pathway in fat cell-mediated aldosterone secretion.
We then evaluated possible interactions of the ERK1/2 MAPKs and the Wnt signalling pathways in adipocyte-induced adrenocortical aldosterone secretion. Exposure of human adrenocortical NCI H295R cells to Wnt-3a did not affect ERK 1/2-activation. Accordingly, fat cell-induced ERK1/2 phosphorylation was not inhibited by the Wnt-antagonist sFRP-1.
Therefore, ERK1/2 MAPKs pathway and the Wnt signalling pathway seem to be two independent mechanisms in adipocyte-mediated aldosterone secretion. These mechanisms might be important in the development of obesity hypertension.
03 - 07 May 2008
European Society of Endocrinology