Mechanism of action of endothelins on adrenocortical cells.

Endothelins (ETs) play a pivotal role in the control of various endocrine and neuroendocrine tissues. In this review, we discuss the involvement of ETs as possible regulators of steroid secretion and we describe the mechanism of action of ETs on adrenocortical cells. The occurrence 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 presence of ETs has also been detected in pheochromocytomas. In vitro studies have shown that ETs stimulate aldosterone secretion by adrenal tissues in various mammalian and amphibian animal models. The receptor subtype involved in the corticotropic action of ETs clearly differs among the various vertebrate species studied. In rat, the effect of ETs is mediated through an ET(B) receptor subtype while, in frog, an ET(A) receptor is implicated in the stimulatory action of ETs. In human adrenocortical cells, both ET(A) and ET(B) receptor subtypes are involved in the corticotropic effect of ETs. Activation of adrenal receptors causes an elevation of inositol trisphosphates associated with an increase in cytosolic calcium concentration. In addition, ETs induce an elevation of prostaglandin E2 (PGE2) and prostacyclin PGI2 production in the adrenal tissue, indicating that prostanoids may act as second messengers of ETs. It thus appears that ETs present in the adrenal gland may act as paracrine factors to stimulate the secretory activity of adrenocortical cells.