Thyrotropin-Releasing Hormone Stimulation of Prolactin Secretion Is Coordinately but Not Synergistically Regulated by an Elevation of Cytoplasmic Calcium and 1,2-Diacylglycerol*

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Abstract
The precise roles of the calcium and lipid pathways in TRH-stimulated PRL secretion from rat pituitary (GH3) cells are controversial. In particular, it is debated whether elevation of cytoplasmic free Ca2+ concentration ([Ca2+]i) is sufficient to cause burst secretion (0-2 min) or whether an increase in 1,2-diacylglycerol must accompany the Ca2+ elevation. In this study, the effects of TRH, which elevates 1,2-diacylglycerol, on [Ca2+]i and stimulation of burst secretion were compared with those of depolarization by high extracellular K+, which does not increase 1,2-diacylglycerol. A maximal concentration of TRH (1 .mu.M) and depolarization by 17.5 mM K+ caused elevation of [Ca2+]i from the resting level of 140 .+-. 20 nM to 470 .+-. 70 nM and 514 .+-. 60 nM, respectively, and stimulated burst secretion from 0.6 .+-. 0.2 ng/106 cells/min to 3.3 .+-. 0.8 and 3.1 .+-. 0.4 ng/106 cells/min, respectively, when a small component of TRH-stimulated secretion that is independent of elevation of [Ca2+]i was subtracted. A detailed comparison of multiple levels to which [Ca2+]i was elevated (up to 600 nM) and the degree of stimulation of burst phase secretion demonstrated the same positive linear correlation (correlation coefficient = 0.96) for TRH and K+ depolarization. Hence, elevation of [Ca2+]i is sufficient to cause burst secretion irrespective of elevation of 1,2-diacylglycerol. Optimal stimulation by TRH sustained secretion of PRL did not depend on elevation of [Ca2+]i; sustained PRL secretion stimulated by 10 nM TRH was 2.6 .+-. 0.4 and 2.7 .+-. 0.2 ng/106 cells/min in control cells and arachidonic acid-pretreated cells in which [Ca2+]i was not elevated, respectively. The data from this and previous studies demonstrate that elevation of [Ca2+]i and 1,2-diacyglycerol may act coordinately, but not synergistically, to mediate TRH stimulation of PRL secretion from GH3 cells.

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