Differences inthe interaction between dopamine and estradiol onprolactin release bycultured normal and tumorous human pituitary cells

Westudied the interaction between dopamine and estradiol onPRL release bycultured normal and tumorous PRL-secreting cells prepared from human pituitaries. If pituitary glands were obtained within 3 h after sudden death of previously normal individuals, theviability of isolated pituitary cells prepared by dispersion with dispase was more than75%. After 4days ofcultur, dopamine (500 nM) inhibited PRL release by cells prepared from four normal pituitaries by 24±3%(±SEM). Pretreatment of the cells with 100 nM estradiol did not alter dopamine-mediated inhibition of PRL release. Estradiol alone increased basal PRL release andcell PRL content.Cultured PRL-secreting pituitary tumor cells, obtained by transsphenoidal operation from four patients, were similarly sensitive to dopamine. Estradiol stimulated tumor cell PRL releaseand content, but significantly diminished the inhibitory effect of dopamine. Theestrogen receptor blocker tamoxifen didnotalter PRL release, butitdidreverse theestradiol-induced insensitivity of the prolactinoma cells tothedopamine agonist bromocriptine. In conclusion, these invitro results indicate that estrogensdo notantagonize theeffect of dopamine on normal human PRL-secreting pituitary cells. In human pituitarytumor cells, how-ever, estradiol decreased the sensitivity of PRL release to do-pamine (agonists), andthe estrogen action canbe acutely reversed by tamoxifen.