SEROTONERGIC REGULATION OF ADRENOCORTICAL FUNCTION

Serotonin (5-HT) plays a pivotal role in the regulation of the hypotha lamo-pituitary-adrenal axis. In particular, 5-HT is involved in the st imulation of ACTH secretion during stress. Recent data indicate that, at the adrenal level, 5-HT acts as a local regulator of corticosteroid secretion. The presence of 5-HT in the adrenal gland has been demonst rated immunohistochemically and biochemically in various species inclu ding frog, mouse, rat and human. In the mouse, 5-HT has been detected in nerve fibers while, in the frog and rat, 5-HT appears to be sequest ered in chromaffin cells. In man, 5-HT is stored in perivascular mast cells. In vivo and in vitro studies have shown that 5-HT stimulates mi neralo- and glucocorticoid secretion from adrenal cells. In rat, the t ype of receptor involved in the corticotropic effect of 5-HT is still controversial. In the frog and the human, the effect of 5-HT on the ad renal cortex is mediated through a 5-HT4 receptor subtype positively c oupled to adenylyl cyclase and calcium influx. Clinical studies indica te that 5-HT4 receptor agonists stimulate aldosterone secretion in hea lthy volunteers and in patients with aldosterone disorders. The 5-HT4 receptor agonist cisapride and angiotensin II exert additive effects o n aldosterone secretion. In contrast, cisapride has no influence on AC TH-induced aldosterone release. Collectively, these findings suggest t hat intra-adrenal 5-HT stimulates the secretory activity of adrenocort ical cells through a paracrine mode of communication involving a 5-HT4 receptor type. Serotonergic control of corticosteroid production may be involved in the physiological control of the activity of the adrena l cortex, in particular during inflammatory stress. 5-HT may also be i mplicated in the pathophysiology of aldosterone disorders.