Prolactin secretion from human prolactinomas perifused in vitro: effect of TRH, prostaglandin E1, theophylline, dopamine and dopamine receptor blockers

Abstract. To clarify the functional characteristics of prolactin (Prl)-producing adenoma cells, the effect of TRH, prostaglandin E1(PGE1), theophylline, dopamine and dopaminergic antagonists on Prl secretion was examined in vitro in perifused pituitary adenoma tissues obtained at surgery from 8 patients with prolactinoma. Perifusion with TRH at a concentration of 10−6to 10−5mresulted in a significant increase in effluent Prl levels in 3 of the 8 adenoma tissues. In the remaining 5 adenomas, TRH produced no effect on Prl release in vitro. On the other hand, PGE1(10−5m) stimulated Prl secretion in 2 of the 4 adenomas examined. Addition of theophylline (5.5 mm) caused a marked increase of effluent Prl levels in all 8 prolactinomas regardless of the reactivity to TRH or PGE1.Dopamine (5 × 10−7m) suppressed Prl secretion from adenoma tissue in 5 of 7 patients tested but had no effect in the remaining two adenomas. When perifused simultaneously with dopamine, sulpiride (D2-selective dopamine receptor blocker, 5 × 10−7m) blocked the inhibitory effect of dopamine on Prl release in 3 of the 4 dopamine-sensitive prolactinomas. In one adenoma responsive to dopamine but resistant to sulpiride, YM-09151-2 (relatively specific D1-dopamine receptor blocker, 5 × 10−7m) antagonized the dopaminergic inhibition of Prl release. When perifused alone, neither sulpiride nor YM-09151-2 affected Prl release from any of the adenoma tissues tested.These findings suggest that a direct action of TRH on the adenoma cells in stimulating Prl release may be lacking in some prolactinoma cells, and that quantitative and qualitative changes in the dopaminergic inhibition of Prl release may occur in some adenomatous lactotrophs.