CALCITRIOL ATTENUATES THE THYROTROPIN-RELEASING HORMONE-STIMULATED INOSITOL PHOSPHATE PRODUCTION IN CLONAL RAT PITUITARY (GH4C1) CELLS

Three days pretreatment of the prolactin (PRL) secreting GH4C1 cells w ith 10 nM calcitriol attenuated both the basal and thyrotropin-releasi ng hormone (TRH)-stimulated (1 muM, 5 s) inositol trisphosphate (IP3) production by 30 and 26%, respectively. The effect was detectable at 1 0 nM (basal) and 1 pM (TRH-stimulated), and maximal at 1 muM (basal) a nd 10 nM (TRH), respectively. Calcitriol was at least 100 times more p otent than calcidiol and 24-hydroxycalcidiol, and the effect was rever sible upon cessation of pretreatment. Calcitriol pretreatment (1 muM, 5 days) also decreased the levels of phosphatidyl-inositol, phosphatid ylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate by 23 , 55 and 32%, respectively. GTPgammaS-stimulated (100 muM, 30 s) IP3 p roduction was decreased by 45% after calcitriol pretreatment (10 nM, 5 days). Pertussis toxin (1 nM, 4 h) attenuated both the basal and TRH- stimulated IP3 production, but this effect was omitted by calcitriol p retreatment. Thus, calcitriol specifically attenuates both the basal a nd TRH-stimulated inositol phosphate production in GH4C1 cells. The me chanism, at least partly, involves decreased availability of phosphoin ositides for phospholipase C. Calcitriol regulation of a pertussis tox in-sensitive G-protein might also play some role.