Inhibition by glucocorticoids of PGE2 and ACTH secretion induced by phorbol esters and EGF in rat pituitary cells.
In rat pituitary cells in primary culture glucocorticoids specifically inhibit PGE2 and ACTH secretions induced by TPA, a potent phorbol ester derivative (triamcinolone acetonide greater than dexamethasone greater than cortisol greater than or equal to corticosterone). However, while PGE2 secretion can be inhibited up to 80%, ACTH secretion can only be inhibited up to 40%. Similar inhibitory effects are observed with mepacrine, an inhibitor of phospholipase A2 (PLA2). Glucocorticoids having also been described as PLA2-inhibitors, their inhibitory effect on TPA-induced secretions could thus be related to their anti-PLA2 activity. Their inhibitory effect on PLA2 has been attributed to their ability to induce the synthesis of lipocortin, the activity of which could be regulated by activation of kinase C or EGF-receptor kinase. Since in our model, EGF-induced PGE2 secretion is also inhibited by dexamethasone, these results suggest that a lipocortin-like protein could be present in pituitary cells and involved in the effect of TPA and EGF on PGE2, and, at least partly, on ACTH release.
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Centre de Recherches Roussel-Uclaf, Romainville, France.
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D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone; D005938:Glucocorticoids / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D010703:Phorbol Esters / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011458:Prostaglandins E / Q000378:metabolism*; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014222:Triamcinolone Acetonide / Q000494:pharmacology
D002273:Carcinogens; D005938:Glucocorticoids; D010703:Phorbol Esters; D011458:Prostaglandins E; C008876:phorbol-12,13-didecanoate; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D014222:Triamcinolone Acetonide; D011796:Quinacrine; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate