G. Sornes et al., CALCITRIOL ATTENUATES THE THYROTROPIN-RELEASING HORMONE-STIMULATED INOSITOL PHOSPHATE PRODUCTION IN CLONAL RAT PITUITARY (GH4C1) CELLS, Molecular and cellular endocrinology, 93(2), 1993, pp. 149-156
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.