The Role of Endothelins in the Paracrine Control of the Secretion and Growth of the Adrenal Cortex

Abstract

Endothelins (ETs) are a family of vasoactive peptides (ET-1, ET-2, and ET-3) mainly secreted by vascular endothelium and widely distributed in the various body systems, where they play major autocrine/paracrine regulatory functions, acting via two subtypes of receptors (ETA and ETB): Adrenal cortex synthesizes and releases ETS and expresses both ETA and ETB. Zona glomerulosa possesses both ETA and ETB, whereas zona fasciculata/reticularis is almost exclusively provided with ETB. ETS exert a strong mineralocorticoid and a less intense glucocorticoid secretagogue action, mainly via ETB receptors. ETS also appear to enhance the growth and steroidogenic capacity of zona glomerulosa and to stimulate its proliferative activity. This trophic action of ETS is likely to be mediated mainly by ETA receptors. The intraadrenal release of ETS undergoes a multiple regulation, with the rise in blood flow rate and the local release of nitric oxide being the main stimulatory factors. Data are also available that indicate that ETS may also have a role in the pathophysiology of primary aldosteronism caused by adrenal adenomas and carcinomas.