title: Novel insights into the potential involvement of 5-HT7 receptors in endocrine dysregulation in stress-related disorders.
abstract: A hyperactive hypothalamic-pituitary-adrenal (HPA) axis is a common feature of stress-related disorders, and the brain serotonin (5-HT) system plays a major role in HPA axis modulation. Glucocorticoids and stress profoundly affect the 5-HT system so it is possible that alterations of endocrine 5-HT mechanisms may underlie HPA axis overdrive in stress-related diseases. Available evidence suggests a role of 5-HT1A, 5-HT2A/2C and 5-HT7 receptors in HPA system activation, and pharmacological blockade of 5-HT7 receptors produces a fast-acting antidepressant-like action and shortens the onset of antidepressant-like effects of various classes of antidepressants. The mechanisms involved in this effect have not been elucidated, but recent findings suggest a role of 5-HT7 receptors in the development of HPA axis overdrive as a result of chronic stress. Remarkably, clinical findings have shown an association between corticosteroid-producing adenomas and expression of ectopic 5-HT7 receptors in corticosteroid-producing adrenocortical cells. These observations might therefore reveal an endocrine mechanism for the antidepressant-like action of 5-HT7 receptor blockers, possibly through normalization of HPA axis function. If such a preliminary hypothesis is confirmed, the potential therapeutic usefulness of 5-HT7 receptor antagonists could extend beyond depression to include other diseases, the pathophysiology of which has been associated with chronic stress and HPA axis dysregulation.
authors.forename: José A
authors.initials: JA
authors.lastname: Terrón
mesh_terms: D000818:Animals; D001526:Behavioral Symptoms / Q000150:complications*; D004700:Endocrine System Diseases / Q000209:etiology* / Q000378:metabolism*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D010913:Pituitary-Adrenal System / Q000187:drug effects; D011985:Receptors, Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000494:pharmacology
chemical_list: D011985:Receptors, Serotonin; D018490:Serotonin Agents; C104425:serotonin 7 receptor