Glucocorticoids antagonize induction of prolactin-gene expression by calcitriol in rat pituitary tumour cells.
Clonal strains of rat pituitary tumour (GH4C1) cells are known to possess specific intracellular binding sites for calcitriol (1,25-dihydroxycholecalciferol, 1,25-dihydroxyvitamin D3). GH4C1 cells respond to calcitriol by a selective increase in prolactin(PRL)-gene expression. The interaction between calcitriol and glucocorticoids was studied by using this cultured-cell model. It was found that cortisol potently antagonized the induction of PRL mRNA and PRL production by calcitriol. The effects were concentration-dependent and were evident at glucocorticoid concentrations that did not alter basal PRL production. Inhibition was half-maximal at 3.2 nM-cortisol and 0.4 nM-dexamethasone. Calcitriol-induced PRL mRNA fell by more than 50% at 25 h and reached the control level 50 h after treatment with cortisol. The inhibition by cortisol of calcitriol induction of PRL production was selective when compared with effects on other inducers of PRL-gene expression [thyroliberin, epidermal growth factor and phorbol myristate acetate ('12-omicron-tetradecanoylphorbol 13-acetate')]. Potent antagonism by glucocorticoids of vitamin D action on specific gene expression has been demonstrated. Further studies with this cultured-cell model may help to explain the mechanism of this hormonal interaction, which assumes particular importance at major sites of vitamin D action such as the intestine.
Wark
J D
JD
Gurtler
V
V
D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000494:pharmacology*; D006854:Hydrocortisone / Q000494:pharmacology; D008297:Male; D010911:Pituitary Neoplasms / Q000235:genetics*; D011388:Prolactin / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology
D005938:Glucocorticoids; D012333:RNA, Messenger; D013973:Thyrotropin-Releasing Hormone; D004815:Epidermal Growth Factor; D011388:Prolactin; D002117:Calcitriol; D013755:Tetradecanoylphorbol Acetate; D006854:Hydrocortisone