Differential regulation of beta 1- and beta 2-adrenergic receptor protein and mRNA levels by glucocorticoids during 3T3-F442A adipose differentiation.
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.[1]References
- Differential regulation of beta 1- and beta 2-adrenergic receptor protein and mRNA levels by glucocorticoids during 3T3-F442A adipose differentiation. Fève, B., Emorine, L.J., Briend-Sutren, M.M., Lasnier, F., Strosberg, A.D., Pairault, J. J. Biol. Chem. (1990) [Pubmed]
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