β₂-Adrenergic receptors in hamster smooth muscle cells are transcriptionally regulated by glucocorticoids

Steroid hormones modulate adrenergic receptor responsiveness and receptor number. To investigate the regulation of the β2-adrenergic receptor gene by glucocorticoids we examined the effects of the synthetic glucocorticoid agonist triamcinolone acetonide on the expression of β2-adrenergic receptors in DDT1MF-2 hamster smooth muscle cells. Glucocorticoid treatment (1 x 10-7 M) produced a 2.2 ± 0.4-fold (n = 8) increase in β2-adrenergic receptor number (maximum between 6 and 12 h) as determined by radioligand binding and a similar increase in catecholamine-stimulated adenylate cyclase activity. Steady-state levels of β2-adrenergic receptor mRNA, analyzed by Northern blot hybridization, were increased 2.4 ± 0.4-fold (n = 6) within 1 h, while actin mRNA levels were unchanged throughout the experiment. These steroid-induced increases in β2-adrenergic receptor mRNA returned to control levels by 24 h and were followed by a much slower decline in β2-adrenergic receptor in plasma membranes. The rate of β2-adrenergic receptor gene transcription, assessed by nuclear run-off transcription assays, increased 3.1 ± 0.1-fold (n = 2) in cells treated for 30 min with 1 x 10-7 M triamcinolone acetonide. These studies indicate that glucocorticoids regulate the β2-adrenergic receptor-adenylate cyclase system by controlling the rate of transcription of the β2-adrenergic receptor gene and hence the responsiveness of the enzyme to catecholamine stimulation.

Duke Scholars

Author Robert J. Lefkowitz Medicine, Cardiology