Serotonin receptors and neuroendocrine responses

There is extensive pharmacologic evidence that serotonin receptors in the brain can activate the hypothalamic-pituitary-adrenocortical (HPA) axis in rats. Direct-acting serotonin agonists, serotonin uptake inhibitors, serotonin releasers and the serotonin precursor L-5-hydroxytryptophan all increase adrenocorticotrophin (ACTH) and corticosterone release. Serotonin-containing nerve terminals make synaptic contact with corticotrophin-releasing factor (CRF)-containing cells in rat hypothalamus, and serotonin and serotonin agonists stimulate CRF release from isolated rat hypothalamus in vitro. Current evidence, based partly on the ability of selective serotonin receptor antagonists to prevent the increases in ACTH and corticosterone in rats in vivo, implicates 5-HT1A and 5-HT2/5-HT1C receptor subtypes in regulating CRF secretion. The physiologic roles of serotonergic regulation of the HPA axis are not well understood. Serotonin neurons also appear to influence the secretion of other pituitary hormones, especially prolactin and gonadotropins.