Effects of thyroliberin and 4-aminopyridine on action potentials and prolactin release and synthesis in rat pituitary cells in culture.

Effects of thyroliberin (TRH) and 4-aminopyridine (4AP) were studied on prolactin (PRL) secreting rat pituitary tumour cells in culture (GH3 cells). Intracellular recordings obtained from the same cell before and during TRH stimulation showed this peptide to increase the spontaneous firing frequency and prolong the Ca2+ dependent action potentials. These effects were mimicked by 4 AP, which acts by interfering selectively with voltage dependent ionic channels without affecting resting membrane properties. Optimal doses of TRH and 4AP approximately doubled the release of PRL. In contrast, TRH increased PRL synthesis 1.9-fold while 4AP had no effect. Increased PRL synthesis is thus not a direct consequence of the hormone release. We conclude that TRH and 4AP both stimulates PRL release via the facilitating effects on the action potentials. TRH has additional intracellular effects which lead to increased synthesis of the hormone. The effects of TRH responsible for stimulation of PRL synthesis are not causally related to the impulse activity of the surface membrane of the cell.