Glucocorticoid regulation of beta-adrenergic receptors in 3T3-L1 preadipocytes.
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.
D000273:Adipose Tissue / Q000166:cytology* / Q000187:drug effects; D000526:Alprenolol / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D020120:Iodocyanopindolol; D007700:Kinetics; D008566:Membranes / Q000378:metabolism; D051379:Mice; D009638:Norepinephrine / Q000494:pharmacology; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D014415:Tunicamycin / Q000494:pharmacology
D005938:Glucocorticoids; D011943:Receptors, Adrenergic, beta; D014415:Tunicamycin; D003609:Dactinomycin; D005576:Colforsin; D003907:Dexamethasone; D020120:Iodocyanopindolol; D000526:Alprenolol; D003513:Cycloheximide; D010869:Pindolol; D000242:Cyclic AMP; D009638:Norepinephrine; D004837:Epinephrine