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 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.
Sørnes
G
G
Hormone Laboratory, Aker Hospital, Oslo, Norway.
Haug
E
E
Torjesen
P A
PA
D015650:24,25-Dihydroxyvitamin D 3; D000818:Animals; D002112:Calcifediol / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002999:Clone Cells / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006887:Hydroxycholecalciferols / Q000494:pharmacology; D007295:Inositol Phosphates / Q000096:biosynthesis*; D008563:Membrane Lipids / Q000378:metabolism*; D037342:Pertussis Toxin; D010716:Phosphatidylinositols / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000378:metabolism / Q000473:pathology; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D013973:Thyrotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D006887:Hydroxycholecalciferols; D007295:Inositol Phosphates; D008563:Membrane Lipids; D010716:Phosphatidylinositols; D010566:Virulence Factors, Bordetella; C030711:24-hydroxyvitamin D3; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D015650:24,25-Dihydroxyvitamin D 3; D013973:Thyrotropin-Releasing Hormone; D011388:Prolactin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D002117:Calcitriol; D002112:Calcifediol; D002118:Calcium