MECHANISM OF ACTION OF ENDOTHELINS ON ADRENOCORTICAL-CELLS

Endothelins (ETs) play a pivotal role in the control of various endocr ine and neuroendocrine tissues. In this review, we discuss the involve ment of ETs as possible regulators of steroid secretion and we describ e the mechanism of action of ETs on adrenocortical cells. The occurren ce of ETs has been demonstrated in the human, porcine and rat adrenal gland, in humans, immunohistochemical and biochemical techniques have reported that ETs are localized exclusively in the cortex but the pres ence of ETs has also been detected in pheochromocytomas. In vitro stud ies have shown that ETs stimulate aldosterone secretion by adrenal tis sues in various mammalian and amphibian animal models. The receptor su btype involved in the corticotropic action of ETs clearly differs amon g the various vertebrate species studied. In rat, the effect of ETs is mediated through an ETB receptor subtype while, in frog, an ETA recep tor is implicated in the stimulatory action of ETs. In human adrenocor tical cells, both ETA and ETB receptor subtypes are involved in the co rticotropic effect of ETs. Activation of adrenal receptors causes an e levation of inositol trisphosphates associated with an increase in cyt osolic calcium concentration. In addition, ETs induce an elevation of prostaglandin E-2 (PGE(2)) and prostacyclin PGl(2) production in the a drenal tissue, indicating that prostanoids may act as second messenger s of ETs. It thus appears that ETs present in the adrenal gland may ac t as paracrine factors to stimulate the secretory activity of adrenoco rtical cells.