Dexamethasone inhibits the release of TSH from the rat anterior pituitary gland in vitro by mechanisms dependent on de novo protein synthesis and lipocortin 1

Abstract

Glucocorticoids have been shown repeatedly to inhibit the secretion of TSH in experimental animals and in man but their site and mode of action are unknown. In the present study, we have used an in vitro model to examine the effects of dexamethasone on the resting and pharmacologically evoked secretion of TSH by the rat anterior pituitary gland, and to show how they are influenced by inhibitors of RNA/protein synthesis. In addition, we have investigated the potential role of lipocortin 1 (LC1), a protein shown previously to contribute to glucocorticoid action in several systems, as a mediator of the glucocorticoid-induced suppression of TSH release in our in vitro preparation. The significant (PP2+ channel opener BAY K8644 (10 μmol/l) was unaffected by the steroid, although readily antagonised (P2+-dependent mechanism. Exposure of the tissue to dexamethasone (0·1 μmol/l) caused a pronounced increase in the amount of cellular LC1 attached to the outer surface of the cells and a concomitant decrease in the intracellular LC1 pool. Progesterone (0·1 μmol/l) and aldosterone (0·1 μmol/l) were also weakly active in this regard, but thyroxine and tri-iodothyronine (0·1 μmol/l) were not. Addition of an N-terminal LC1 fragment, LC1(1–188) (0·05–0·53 pmol/l) to the incubation medium reduced significantly (PPPde novo RNA/protein synthesis and that they involve an LC1 dependent mechanism. Journal of Endocrinology (1995) 147, 533–544