Transient Removal of Dopamine Potentiates the Stimulation of Prolactin Release by TRH but Not VIP: Stimulation via Ca ^{2 +}/Protein Kinase C Pathway

Abstract

The effectiveness of thyrotropin-releasing hormone (TRH) and vasoactive intestinal peptide (VIP) to release prolactin (PRL) after a brief interruption of the tonic inhibitory action of dopamine (DA) was investigated in enzymatically dispersed anterior pituitary cells in superfusion. We also studied the involvement of cAMP and Ca^{2 +} /protein kinase C second messenger systems in the mediation of the stimulated PRL release. Anterior pituitary cells from lactating or E2-treated rats were superfused for 10 min with secretagogues either during continual dopamine administration or 10–20 min after a 10-min transient interruption of DA (500 n M). Removal of DA for 10 min resulted in a significant increase in PRL release which had returned to basal levels 10 min after the return of DA to the superfusion. During continuous DA exposure, TRH administration (10 n M) did not alter the rate of PRL release from cells from lactating rats; however, TRH caused a 2-fold increase after the transient interruption of DA. The transient escape from DA inhibition also increased the effectiveness of TRH (100 n M) to release PRL from cells from E2-treated rats (from a 4- to a 15-fold stimulation). In contrast, VIP (0.5 or 5 µ M) caused a 2-fold stimulation of PRL release in both cells treated with continuous or transiently interrupted DA. The transient removal of DA also potentiated PRL release induced by treatment with the Ca^{2 +} ionophore A23187 (5 and 20 µ M) and/or the protein kinase C stimulator 12–0-tetradecanoyl-phorbol-3-acetate (TPA) (50 n M), but not following treatment with the adenylate cyclase activator forskolin (10 µ M) or the cAMP analog 8-Br-cAMP (2.5 m M). These data suggest that a transient escape from DA inhibition increases the responsiveness of lactotrophs to the PRL-re-leasing action of TRH but not to VIP. It appears that the potentiated action of TRH involves a Ca^{2 +} /protein kinase C-mediated pathway.