Serotonergic regulation of adrenocortical function.
Serotonin (5-HT) plays a pivotal role in the regulation of the hypothalamo-pituitary-adrenal axis. In particular, 5-HT is involved in the stimulation 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 demonstrated immunohistochemically and biochemically in various species including 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 sequestered 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 mineralo- and glucocorticoid secretion from adrenal cells. In rat, the type 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 adrenal cortex is mediated through a 5-HT4 receptor subtype positively coupled to adenylyl cyclase and calcium influx. Clinical studies indicate that 5-HT4 receptor agonists stimulate aldosterone secretion in healthy volunteers and in patients with aldosterone disorders. The 5-HT4 receptor agonist cisapride and angiotensin II exert additive effects on aldosterone secretion. In contrast, cisapride has no influence on ACTH-induced aldosterone release. Collectively, these findings suggest that intra-adrenal 5-HT stimulates the secretory activity of adrenocortical 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 adrenal cortex, in particular during inflammatory stress. 5-HT may also be implicated in the pathophysiology of aldosterone disorders.
Lefebvre
H
H
European Institute for Peptide Research, Group for Hormone Research, CHU of Rouen, France.
Contesse
V
V
Delarue
C
C
Vaudry
H
H
Kuhn
J M
JM
D000302:Adrenal Cortex / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D000305:Adrenal Cortex Hormones / Q000096:biosynthesis / Q000097:blood; D000818:Animals; D006801:Humans; D011985:Receptors, Serotonin / Q000502:physiology; D012701:Serotonin / Q000032:analysis / Q000494:pharmacology / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D000305:Adrenal Cortex Hormones; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D012701:Serotonin