Evidence for the Role of Calcium and Diacylglycerol as Dual Second Messengers in Thyrotropin-Releasing Hormone Action: Involvement of Diacylglycerol*

Abstract

TRH stimulates the secretion of PRL [prolactin] by clonal [rat] GH3 pituitary cells. The secretory response during the first 30-60 min is biphasic (phase I, 0-3 min; phase II, 5-60 min); the phase I response may be mediated through mechanisms involving Ca+2 translocation. TRH treatment has rapidly induced the breakdown of inositol phospholipids with accompanying diacylglycerol accumulation. Evidence for a possible role for diacylglycerol as a 2nd messenger which mediates the phase II response to TRH is presented. A role for lipid-dependent mechanisms in regulating PRL secretion in GH3 cells was supported by the finding that phospholipase C, phorbol esters, melittin, and exogenous diacylglycerols were effective secretagogues in GH3 cells. Secretion promoted by these agents was persistent, as was the phase II response to TRH. For 3 of the agents examined (TRH, phorbol esters and phospholipase C), stimulated PRL release was nonadditive, suggesting the presence of some common element in the pathways by which these agents exert their effects. This lipid-linked pathway of activation was distinguished from a cAMP-mediated pathway.