Steroid inhibition of calcitriol-induced prolactin production in GH4C1 cells. Specificity and sensitivity.
The induction of prolactin (PRL)-gene expression by calcitriol (1,25-dihydroxyvitamin D3, 1,25-dihydroxycholecalciferol) in clonal rat pituitary tumour (GH4C1) cells was selectively inhibited by cortisol [IC50 (concentration causing 50% inhibition) = 3.2-4.1 nM]. The steroid specificity of this effect was investigated and various steroids were found to inhibit calcitriol-stimulated PRL production with the following relative potencies: cortisol, 1; dexamethasone, 8; 11-deoxycortisol, 0.5; corticosterone, 0.4; aldosterone, 0.07; testosterone and oestradiol, less than 0.003. The steroid antagonist RU 38486 did not affect basal or calcitriol-stimulated PRL production, but antagonized the effect of 10 nM-cortisol in a concentration-dependent manner. Neither progesterone nor 11-deoxycortisol antagonized the effect of 10 nM-cortisol. Calcitriol-induced PRL production was 14 times more sensitive to dexamethasone inhibition than was non-stimulated PRL production. Growth-hormone production was stimulated by dexamethasone, in the presence or absence of calcitriol, with a concentration-dependence similar to that of dexamethasone inhibition of basal PRL production. These data indicate that steroid inhibition of calcitriol-stimulated PRL production is a specific glucocorticoid effect. The sensitivity of calcitriol-stimulated PRL production to dexamethasone was 14-26-fold greater than that of other measured responses in the same cells. Two of the possible explanations for this selectively increased sensitivity to glucocorticoids are: amplification of the glucocorticoid effect via an induced mediator; and the presence of very-high-affinity glucocorticoid-receptor-binding sites on DNA.
D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002478:Cells, Cultured; D003345:Corticosterone / Q000494:pharmacology; D003350:Cortodoxone / Q000494:pharmacology; D003864:Depression, Chemical; D003907:Dexamethasone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D006854:Hydrocortisone / Q000494:pharmacology; D015735:Mifepristone; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D013256:Steroids / Q000494:pharmacology*; D013739:Testosterone / Q000494:pharmacology
D004963:Estrenes; D013256:Steroids; D015735:Mifepristone; D013739:Testosterone; D000450:Aldosterone; D004958:Estradiol; D003907:Dexamethasone; D011388:Prolactin; D002117:Calcitriol; D003345:Corticosterone; D003350:Cortodoxone; D006854:Hydrocortisone