Endothelins as local activators of adrenocortical cells

Besides the classical corticotropic hormones, ACTH and angiotensin II, various regulatory peptides produced by the adrenal gland are thought to participate in the control of corticosteroid secretion. Here, we review the evidence that endothelins (ETs) synthesized within the adrenal cortex may act as autocrine and/or paracrine factors to regulate adrenocortical cell activity. The expression of ETs has been detected in normal, hyperplastic and neoplastic adrenocortical cells. The occurrence of ET receptors has been described in the different zones of the cortex. ETs stimulate the secretion of both glucocorticoids and mineralocorticoids, and modulate the proliferation of adrenocortical cells. The effects of ETs on steroidogenic cells are mediated through the activation of various signaling mechanisms including stimulation of phospholipase C, phospholipase A ₂ and adenylyl cyclase activity, as well as calcium influx through plasma channels. These observations suggest that locally produced ETs may play an important role in the regulation of corticosteroid secretion and in the control of mitogenesis in normal and tumoral adrenocortical cells.