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
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 E2 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.