24-hydroxyvitamin-d3 and Pituitary-Neoplasms

Three days pretreatment of the prolactin (PRL) secreting GH4C1 cells with 10 nM calcitriol attenuated both the basal and thyrotropin-releasing hormone (TRH)-stimulated (1 microM, 5 s) inositol trisphosphate (IP3) production by 30 and 26%, respectively. The effect was detectable at 10 nM (basal) and 1 pM (TRH-stimulated), and maximal at 1 microM (basal) and 10 nM (TRH), respectively. Calcitriol was at least 100 times more potent than calcidiol and 24-hydroxycalcidiol, and the effect was reversible upon cessation of pretreatment. Calcitriol pretreatment (1 microM, 5 days) also decreased the levels of phosphatidyl-inositol, phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate by 23, 55 and 32%, respectively. GTP gamma S-stimulated (100 microM, 30 s) IP3 production 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 pretreatment. Thus, calcitriol specifically attenuates both the basal and TRH-stimulated inositol phosphate production in GH4C1 cells. The mechanism, at least partly, involves decreased availability of phosphoinositides for phospholipase C. Calcitriol regulation of a pertussis toxin-sensitive G-protein might also play some role.

Topics: 24,25-Dihydroxyvitamin D 3; Animals; Calcifediol; Calcitriol; Calcium; Clone Cells; GTP-Binding Proteins; Guanosine 5'-O-(3-Thiotriphosphate); Hydroxycholecalciferols; Inositol Phosphates; Membrane Lipids; Pertussis Toxin; Phosphatidylinositols; Pituitary Gland, Anterior; Pituitary Neoplasms; Prolactin; Rats; Signal Transduction; Thyrotropin-Releasing Hormone; Tumor Cells, Cultured; Virulence Factors, Bordetella