title: Estradiol induces expression of 5-hydroxytryptamine (5-HT) 4, 5-HT5, and 5-HT6 receptor messenger ribonucleic acid in rat anterior pituitary cell aggregates and allows prolactin release via the 5-HT4 receptor.
abstract: Serotonin [5-hydroxytryptamine (5-HT)] is known to control prolactin (PRL) release at a hypothalamic level, but a pituitary site of action remains poorly studied. The present study explores the acute effect of 5-HT on PRL release in rat anterior pituitary aggregate cell cultures, the influence of steroid and thyroid hormones, and the 5-HT receptor (5-HTR) subtype(s) involved. 5-HT elicited a prompt increase in basal PRL release, an effect strongly potentiated by estradiol (E(2)) in the culture medium (dose response 1-100 nm). In E(2) condition, the PRL response was not affected by the nonselective 5-HTR antagonists methysergide and methiothepin nor by 5-HTR1, 5-HTR2, 5-HTR3, 5-HTR6, and 5-HTR7/5 antagonists, but was fully blocked by the 5-HTR4 antagonist GR 113808. Among various agonist analogs, only the 5-HTR4 agonist cisapride and the 5-HTR2 agonist alpha-methyl-5-HT evoked PRL release. The effect of alpha-methyl-5-HT also required E(2) during culture and was abolished by GR 113808 but not by combined 5-HTR2A, B, and C blockade. In E(2)-treated aggregates, 5-HT caused a 5-fold increase in cAMP levels. The intact anterior pituitary expressed mRNA of all known members of the 5-HTR family. In aggregates, 5-HTR4, 5-HTR5, and 5-HTR6 mRNA expression required E(2) during culture. The effect of 5-HT on PRL release was not affected by blocking the serotonin transporter or the vesicular monoamine transporter. The present data suggest a widespread expression of 5-HTRs in the rat anterior pituitary, several of which are up-regulated by estrogen, and that, in the presence of estrogen, one of these, the 5-HTR4, mediates acute PRL release.
authors.affiliation: Laboratory of Cell Pharmacology, University of Leuven, Medical School, Campus Gasthuisberg (O & N), B-3000 Leuven, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Papageorgiou
authors.forename: C
authors.initials: C
authors.lastname: Denef
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D037342:Pertussis Toxin / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000378:metabolism*; D044422:Receptors, Serotonin, 5-HT4 / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
chemical_list: D012333:RNA, Messenger; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C078730:serotonin 5 receptor; C097216:serotonin 6 receptor; D044422:Receptors, Serotonin, 5-HT4; D004958:Estradiol; D011388:Prolactin; D000242:Cyclic AMP; D037342:Pertussis Toxin