Endothelial cells modulate aldosterone synthesis in human adrenocortical cells

Endothelial cells play an important role in the development and functioning of endocrine tissue. They populate the adrenal cortex as a part of the capillaries and sinusoids that engulf groups of steroidogenic cells. This arrangement enables sufficient paracrine interaction between the endothelial cells and the steroidogenic cells. Moreover, various endothelial cell-derived factors have been known to regulate mineralocorticoid release. In the present study, we analyzed the role of human endothelial cells in the synthesis and release of aldosterone from adrenocortical cells (NCI-H295R).

The human vein endothelial cells (HUVEC) were used to avail the endothelial cell-conditioned medium (ECM) with which the adrenocortical cells were stimulated to simulate a possible in-vivo paracrine regulation.

We observed that H295R cells treated with ECM for 24h exhibited an enhanced release of aldosterone synthesis by 2.5 folds. Further, the endothelial cell-induced aldosterone release was rapid and lasted as a long term effect over a period of 48h. This stimulant effect was influenced by the duration of endothelial cell conditioning and decreased linearly with increasing dilutions of ECM. At the molecular level, we observed an increase in the mRNA transcripts of aldosterone synthase and StAR. Moreover, ECM interaction with the cortical cells enhanced the activation of CRE, phosphorylation of CREB protein, and the promoter activity of both StAR and SF-1 reporter genes.

In conclusion, human endothelial cells exert a paracrine influence on adrenocortical cell aldosterone synthesis and may function as intraadrenal regulators of human aldosterone synthesis and release in-vivo.