Dexamethasone regulates the β-adrenergic receptor subtype expressed by 3T3-L1 preadipocytes and adipocytes

The subtype of the β-adrenergic receptor expressed in 3T3-L1 preadipocytes and adipocytes differentiated with dexamethasone and methylisobutylxanthine was determined by comparing the affinity of the receptors for epinephrine, norepinephrine, and β-1 and β-2 selective drugs. Receptors in preadipocyte membranes exhibited the same affinity for epinephrine and norepinephrine and bound practolol, a β-1 selective antagonist, 8-fold more avidly than adipocyte receptors. In contrast, adipocyte β-receptors had a 10-fold higher affinity for epinephrine than for norepinephrine and complexed the β-2 selective agonist zinterol with a 20-fold higher affinity than preadipocyte receptors. Hofstee plots and computer analyses of the binding data revealed that the populations of β-1 receptors in preadipocytes and β-2 receptors in adipocytes were nearly homogeneous. Preliminary characterizations of the β-receptor phenotype in (nondifferentiating) 3T3-C2 cells treated with dexamethasone and methylisobutylxanthine and 3T3-422A adipocytes differentiated with insulin indicated that the expression of β-2 receptors was not correlated with differentiation, but rather with exposure of the cells to dexamethasone and methylisobutylxanthine. The regulator of β-receptor subtype was identified as the glucocorticoid analog, dexamethasone, by employing 3T3-L1 adipocytes which were stimulated to differentiate with methylisobutylxanthine and insulin. Detailed binding studies showed that under these conditions the adipocyte receptors retain β-1 character. Subsequent treatment with 0.5 μM dexamethasone promoted the loss of β-1 receptors, the appearance of β-2 receptors, and a net 2- to 3-fold increase in the number of β-receptors. Dexamethasone effected a complete switch from β-1 to β-2 subtype at concentrations as low as 2.5 nM while other steroids were effective below a concentration of 10 μM.