Beta-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 beta 2-adrenergic receptor gene by glucocorticoids we examined the effects of the synthetic glucocorticoid agonist triamcinolone acetonide on the expression of beta 2-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 beta 2-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 beta 2-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 beta 2-adrenergic receptor mRNA returned to control levels by 24 h and were followed by a much slower decline in beta 2-adrenergic receptor in plasma membranes. The rate of beta 2-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 beta 2-adrenergic receptor-adenylate cyclase system by controlling the rate of transcription of the beta 2-adrenergic receptor gene and hence the responsiveness of the enzyme to catecholamine stimulation.
Collins
S
S
Howard Hughes Medical Institute, Duke University Medical Center, Department of Medicine, Durham, North Carolina 27710.
Caron
M G
MG
Lefkowitz
R J
RJ
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D005786:Gene Expression Regulation / Q000187:drug effects*; D005796:Genes / Q000187:drug effects*; D009130:Muscle, Smooth / Q000378:metabolism*; D009693:Nucleic Acid Hybridization; D010957:Plasmids; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D011943:Receptors, Adrenergic, beta / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014222:Triamcinolone Acetonide / Q000494:pharmacology*
D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D000262:Adenylyl Cyclases; D014222:Triamcinolone Acetonide