Role of Serotonin in the Paracrine Control of Adrenal Steroidogenesis in Physiological and Pathophysiological Conditions

Serotonin (5-hydroxytryptamine, 5-HT) and 5-HT receptors are present in adrenals from various species. In rats and humans, 5-HT mainly stimulates aldosterone secretion through activation of 5-HT7 and 5-HT4 receptors, respectively. The 5-HT-ergic control of adrenal steroidogenesis is strengthened in extreme physiological conditions such as sodium depletion and chronic stress. Especially, the emergence of a 5-HT regulatory loop in glucocorticoid-producing cells may be regarded as an adaptive mechanism aimed at potentiating the glucocorticoid response to stress. In humans, upregulation of the 5-HT signalling pathway occurs in aldosterone-producing adenomas and cortisol-producing hyperplasias and adenomas in response to overactivation of protein kinase A. These data suggest that the intra-adrenal 5-HT-ergic regulatory system represents a potential target for pharmacological treatments of primary adrenocortical diseases.