Evidence that Stimulation of Thyrotropin and Prolactin Secretion by Thyrotropin-Releasing Hormone Occur via Different Calcium-Mediated Mechanisms: Studies with Verapamil*

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Abstract
TRH stimulation of TSH and PRL secretion requires Ca2+. We determined whether influx of extracellular Ca2+ was involved in TRH action in TtT cells (mouse pituitary tumor cells in short term culture that produce TSH), in GH3 cells (clonal rat pituitary tumor cells that produce PRL), and in anterior pituitary cells in vitro derived from normal rats. TRH increased 45Ca2+ uptake by TtT cells by 40% but had no effect on 45Ca2+ uptake by GH3 cells. Verapamil, which totally inhibited 45Ca2+ uptake by TtT and GH3 cells induced by depolarization with 50 mM K+, was employed to block influx of extracellular Ca2+. Verapamil (50 JUM) abolished the increment in 45Ca2+ uptake by TtT cells caused by TRH. Verapamil had no effect on TRH-stimulated 45Ca2+ efflux and PRL release from GH3 cells but partially inhibited TRH-stimulated 45Ca2+ efflux and TSH release from TtT cells during perifusion. TRH-stimulated PRL release from GH3 cells was likewise not affected by verapamil during static incubation (7.2 ± 1.1 ng/ml vs. 6.2 ± 1.2 ng), but TRH-stimulated TSH release from TtT cells was inhibited by 64% (from 5.5 ± 0.7 ngeq/ml to 2.0 ± 0.6 ngeq). Similar findings on the effects of verapamil on hormone release were obtained from nonneoplastic anterior pituitary cells; TRH-stimulated PRL release was not affected, but TRH-stimulated TSH release was inhibited by 50%. Hence, TRH did not cause Ca2+ influx into mammotropic cells and TRH-stimulated PRL release was not affected when Ca2+ influx was blocked by verapamil. In contrast, TRH appeared to cause Ca2+ influx into thyrotropic cells, and TRH-stimulated TSH release was partially inhibited when Ca2+ influx was blocked by verapamil. We suggest that TRH action in mammotrophs involves only mobilization of cellular Ca2+, whereas TRH action in thyrotrophs involves mobilization of cellular Ca2+ and influx of extracellular Ca2+.