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Role of 5-HT in the regulation of the brain-pituitary-adrenal axis: effects of 5-HT on adrenocortical cells

2000; NRC Research Press; Volume: 78; Issue: 12 Linguagem: Inglês

10.1139/y00-098

1205-7541

Vincent Contesse, Hervé Lefèbvre, Sébastien Lenglet, Jean‐Marc Kuhn, Catherine Delarue, Hubert Vaudry,

Hormonal Regulation and Hypertension

Serotonin (5-HT) plays a pivotal role in the regulation of the brain-pituitary-adrenal axis. In particular, 5-HT has been shown to control the activity of hypothalamic CRF neurons and pituitary corticotrope cells through activation of 5-HT 1A and (or) 5-HT 2A/2C receptor subtypes. 5-HT, acting through 5-HT 2 receptors, can also trigger the renin-angiotensin system by stimulating renin secretion and consequently can enhance aldosterone production. At the adrenal level, 5-HT produced locally stimulates the secretory activity of adrenocortical cells through a paracrine mode of communication. The presence of 5-HT in the adrenal gland has been demonstrated immunohistochemically and biochemically in various species. In the frog, rat, and pig adrenal gland, 5-HT is synthesized by chromaffin cells, while in the mouse adrenal cortex, 5-HT is contained in nerve fibers. In man, 5-HT is present in perivascular mast cells. In vivo and in vitro studies have shown that 5-HT stimulates corticosteroid secretion in various species (including human). The type of receptor involved in the mechanism of action of 5-HT differs between the various species. In frogs and humans, the stimulatory effect of 5-HT on adrenocortical cells is mediated through a 5-HT 4 receptor subtype positively coupled to adenylyl cyclase and calcium influx. In the rat, the effect of 5-HT on aldosterone secretion is mediated via activation of 5-HT 7 receptors. Clinical studies indicate that 5-HT 4 receptor agonists stimulate aldosterone secretion in healthy volunteers and in patients with corticotropic insufficiency and primary hyperaldosteronism. Local serotonergic control of corticosteroid production may be involved in the physiological control of the activity of the adrenal cortex as well as in the pathophysiology of cortisol and aldosterone disorders.Key words: HPA axis, renin-angiotensin system, adrenal gland, corticosteroid secretion, serotonergic receptors.