title: Differential regulation of beta 1- and beta 2-adrenergic receptor protein and mRNA levels by glucocorticoids during 3T3-F442A adipose differentiation.
abstract: The regulation by dexamethasone of beta 1- and beta 2-adrenergic receptor expression during the adipose differentiation of 3T3-F442A cells was investigated at the receptor protein and mRNA level. Preadipocytes were poorly responsive to beta-adrenergic receptor (beta-AR) agonists and expressed few beta-ARs (approximately 3,000 sites/cell) solely of beta 1 subtype. Differentiation increased adrenergic sensitivity and total beta-AR number (approximately 16,000 sites/cell) with a beta 1/beta 2 ratio of approximately 90/10. Long term exposure of either differentiating cells or mature adipocytes to dexamethasone induced down-regulation of (-)-isoproterenol-sensitive adenylate cyclase activity which paralleled a 2- to 3.5-fold decrease in beta-ARs, while the beta 1/beta 2 ratio switched to approximately 20/80. The ratios of beta 1/beta 2 binding sites were always consistent with the rank order of potency of beta-adrenergic agonists in stimulating the adenylate cyclase system. The action of steroid agonists and antagonist suggested a glucocorticoid receptor-mediated mechanism. The beta 1-AR mRNA (3.2 kilobases) was stimulated 3-4.7 times in differentiated cells, as compared with preadipose cells; this beta 1-AR transcript was repressed in dexamethasone-treated cells. The beta 2-AR mRNA species (2.3 kilobases), absent in preadipocytes, was expressed at low levels in untreated adipocytes, but reached 11-fold this level in dexamethasone-exposed cells. The switch in receptor subtype protein and mRNA levels elicited by dexamethasone demonstrates the differential genetic control by glucocorticoids of beta-AR subtype expression in 3T3-F442A cells. We suggest that this regulation of beta-AR gene expression requires interactions of glucocorticoid receptors with specific DNA targets and with one (or several) transcription factor(s) that are cell- and differentiation state-dependent.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale-Centre National de la Recherche Scientifique, U 282, Hôpital Henri Mondor, Créteil, France.
authors.forename: B
authors.initials: B
authors.lastname: Fève
authors.forename: L J
authors.initials: LJ
authors.lastname: Emorine
authors.forename: M M
authors.initials: MM
authors.lastname: Briend-Sutren
authors.forename: F
authors.initials: F
authors.lastname: Lasnier
authors.forename: A D
authors.initials: AD
authors.lastname: Strosberg
authors.forename: J
authors.initials: J
authors.lastname: Pairault
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D011412:Propanolamines / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics*; D011943:Receptors, Adrenergic, beta / Q000235:genetics*
chemical_list: D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; C026777:ICI 118551; D003907:Dexamethasone; D000262:Adenylyl Cyclases; D007545:Isoproterenol