title: Regulation of Basal and stimulated prolactin release in prolactin-secreting rat pituitary tumors*.
abstract: Abstract To better understand the mechanisms of the inhibitory effects of dopamine on pituitary prolactin release, we have utilized an estrone-induced, benign and dopamine-sensitive rat pituitary adenoma and two malignant, transplantable and dopamine-resistant rat pituitary tumors, 7315a and MITW15. Enzymatically dispersed and Percoll purified cells obtained from the three tissues were incubated for 30 min in media with or without Na(+) and in the presence or the absence of dopamine and/or various prolactin releasers for evaluating the secretion of prolactin under baseline and experimental conditions. In some experiments, the cells were pretreated for 16 h with pertussis toxin to evaluate the eventual presence and role of pertussis toxin-sensitive G proteins. Dopamine inhibited baseline prolactin release by adenomatous lactotrophs in a Na(+)-dependent manner, but was totally inactive with 7315a and MtTW15 cells. The Ca(2+) channel agonist BAY K 8644 stimulated prolactin release with all three preparations and its effects were enhanced by a Na(+)-free medium. Dopamine antagonized the stimulatory effects of BAY K 8644 with adenomatous and 7315a cells only, even in the absence of Na(+). Pertussis toxin pretreatment significantly increased baseline prolactin release by adenomatous and MtTW15 cells and abolished dopamine inhibition of adenomatous lactotrophs baseline hormone release. BAY K 8644, TRH and vasoactive intestinal peptide, stimulated prolactin release by adenomatous cells and this effect was antagonized by dopamine in a pertussis toxin-sensitive manner. All prolactin releasers, except TRH, were effective also with 7315a cells, and its actions were not blocked by pertussin toxin. The stimulatory effects of BAY K 8644 and vasoactive intestinal peptide on 7315a cells were enhanced by pertussis toxin pretreatment. The results obtained with an almost pure preparation of adenomatous lactotrophs confirm the existence of a dual mechanism of dopamine inhibitory action on prolactin release: 1) a Na(+)-dependent action exerted on baseline, and 2) a Na(+)-independent action exerted on stimulated prolactin release. They also indicate that both actions are exerted through pertussis toxin-sensitive G proteins. Furthermore, our results show the presence in transplantable pituitary tumors 7315a and MtTW15 of multiple and diverse anomalies in the regulation of prolactin release probably due, at least partly, to anomalies of one or more G proteins and/or neurotransmitter receptors.
authors.affiliation: Research Unit on Reproductive and Developmental Biology, Pediatric Research Center, Hôpital Sainte-Justine and Université de Montreal, Montreal, Quebec H3T 1C5, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Lafond
authors.forename: C
authors.initials: C
authors.lastname: Bouvier
authors.forename: H
authors.initials: H
authors.lastname: Forget
authors.forename: G
authors.initials: G
authors.lastname: Lagace
authors.forename: S
authors.initials: S
authors.lastname: Kaufman
authors.forename: R
authors.initials: R
authors.lastname: Collu