Endothelin-1 stimulates steroid secretion of human adrenocortical cells ex vivo via both ETA and ETB receptor subtypes

The role played by endothelins (ETs) and their receptor subtypes (ETA and ETB) 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-l, ET-converting enzyme-1, ETA, and ETB 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 ETA and ETB 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 ETA and ETB receptors, may exert an autocrine/paracrine regulation of the function of the human adrenal cortex.