TY - JOUR T1 - Glucocorticoid regulation of beta-adrenergic receptors in 3T3-L1 preadipocytes. JF - Molecular Pharmacology JO - Mol Pharmacol SP - 377 LP - 384 VL - 31 IS - 4 AU - M T Nakada AU - J M Stadel AU - K S Poksay AU - S T Crooke Y1 - 1987/04/01 UR - http://molpharm.aspetjournals.org/content/31/4/377.abstract N2 - Treatment of 3T3-L1 preadipocytes (fibroblasts) with 250 nM dexamethasone for 48 hr caused a doubling of total beta-adrenergic receptors and an increase in beta 2-adrenergic receptor subtype proportion from approximately 50% in controls to 85% in treated cells. The responses to epinephrine and norepinephrine in a whole cell cAMP accumulation assay reflected these changes. The effects of dexamethasone on beta-adrenergic receptors were mediated through the glucocorticoid receptor and were time and dose dependent with an EC50 of 2.77 +/- 0.73 nM for an increase in the proportion of beta 2-adrenergic receptors. The rank order of potency of steroids to effect these changes (betamethasone = dexamethasone greater than fludrocortisone greater than hydrocortisone = triamcinolone greater than aldosterone) correlated with their glucocorticoid potency. [3H]Dexamethasone binding to intact cells yielded a KD value of 3.47 +/- 0.38 nM for binding to the glucocorticoid receptor which correlated well with the EC50 for dexamethasone to alter beta-adrenergic receptors. Inhibition of [3H]dexamethasone binding by other steroids confirmed that the ability of steroids to regulate beta-adrenergic receptors correlated with the affinity of each compound for the 3T3-L1 glucocorticoid receptor. Progesterone, which can bind to the glucocorticoid receptor but has only weak agonist activity, competitively inhibited the ability of dexamethasone to alter beta-adrenergic receptors. Protein synthesis, RNA synthesis, and N-linked glycosylation appeared to be necessary for the change in receptor subtype expression and the increase in beta-adrenergic receptor number induced by dexamethasone. The present study suggests that regulation of beta-adrenergic receptor expression in 3T3-L1 preadipocytes by dexamethasone is a glucocorticoid-specific effect which may require gene activation. ER -