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Endothelin-1 Stimulates Steroid Secretion of Human Adrenocortical Cells ex Vivo Via Both ET_A and ET_B Receptor Subtypes

Departments of Clinical and Experimental Medicine (G.P.R., G.A., S.H., A.C.P.) and Anatomy (G.N., P.G.A., G.G.N.), University of Padua, I-35121, Padua, Italy

Address all correspondence and requests for reprints to: Prof. Gastone G. Nussdorfer, Department of Anatomy, Via Gabelli 65, I-35121 Padova, Italy. E-mail: ggnanat{at}ipdunidx.unipd.it

The role played by endothelins (ETs) and their receptor subtypes (ET_A and ET_B) in the regulation of steroid hormone secretion in human adrenal gland remains unclear. Therefore, we investigated the gene expression of ET-1 and its receptors in highly pure preparations of human adrenocortical cells and the effect of ET-1 on their secretory activity. Reverse transcription-PCR with primers specific for prepro-ET-1, ET-converting enzyme-1, ET_A, and ET_B complementary DNAs demonstrated the expression of all of these genes in human adrenocortical cells. ET-1 increased the secretion of aldosterone and cortisol by enhancing both earlier and late steps of their synthesis. The secretory response to ET-1 was partially (60%) inhibited by BQ-123 and BQ-788, which are selective antagonists of the ET_A and ET_B receptors, respectively. When added together, the two antagonists suppressed the secretagogue effect of ET-1. Collectively, these findings suggest that ET-1, acting via both ET_A and ET_B receptors, may exert an autocrine/paracrine regulation of the function of the human adrenal cortex.

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