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DOI: 10.1055/s-2006-933060
Steroidogenic action of endothelial cell products on adrenocortical cells in vitro
Objective: The adrenal gland is one of the most vascularized organs in the body. Endothelin (ET)-1, a factor secreted by endothelal cells, was shown to increase aldosterone secretion by cultured adrenocortical cells, and endothelin receptors, including ET-A and ET-B, are thought to be involved.
Methods: We studied the influence of endothelial cell-derived factors on adrenal steroidogenesis in NCI-H295R cells in vitro, using endothelial cell-conditioned medium (ECCM), produced during incubation of HUVEC cells for 24 houres.
Results: Exposure of NCI-H295R cells to ECCM at concentrations of 0%, 1%, 5%, 10%, 20%, and 30% led to a significant increase in the secretion of cortisol and aldosterone in a concentration- and time-dependent manner. Likewise, steroidogenic acute regulatory protein promoter activity was 3.5 times higher in ECCM treated cells and steroidogenic factor-1 dependent promoter activity increased 6-fold as compared to control. These effects were not abolished after pre-treatment of NCI-H295R cells with the endothelin receptor antagonists BQ123 or BQ788, blocking ET-A and ET-B receptor subtypes, respectively, when added at concentrations of 10(-9)M.
Conclusion: We infer that products of endothelial cells are capable in regulating cortisol and aldosterone secretion by adrenal cells in vitro and that these steroidogenic effects are not mediated by endothelin-1, only.