Glucocorticoids induce transcription and expression of the alpha 1B adrenergic receptor gene in DTT1 MF-2 smooth muscle cells.
Steroid hormones modulate physiological processes by a number of mechanisms including regulation of gene expression. We wondered if glucocorticoids might induce expression of alpha 1 adrenergic receptors, which could contribute to the increased sensitivity of vascular smooth muscle to catecholamines that may occur with glucocorticoid excess. We examined the effects of dexamethasone on the expression of the alpha 1B adrenergic receptor gene in DDT1 MF-2 smooth muscle cells. Dexamethasone (10(-6) M) produced a 1.8 +/- 0.2-fold increase in expression of alpha 1B receptors determined with [3H]prazosin. Steady-state values of alpha 1B adrenergic receptor mRNA, analyzed by Northern blotting, increased 2.8 +/- 0.7-fold after 48 h exposure to dexamethasone. This effect of dexamethasone occurred in the presence of the protein synthesis inhibitor cycloheximide. alpha 1B receptor mRNA abundance was also increased by testosterone and aldosterone, whereas beta estradiol and progesterone had no effect. The alpha 1B receptor gene transcription rate, determined in nuclear run-off assays, increased 2.6 +/- 0.6-fold in cells treated with dexamethasone for 24 h. The half-life of the alpha 1B receptor mRNA was unchanged by dexamethasone. These data indicate that glucocorticoids regulate expression of alpha 1B receptors by increasing the rate of transcription of this gene.
Sakaue
M
M
Department of Medicine, Stanford University School of Medicine, Palo Alto, California.
Hoffman
B B
BB
D000818:Animals; D002478:Cells, Cultured; D006224:Cricetinae; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000502:physiology*; D012739:Gonadal Steroid Hormones / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011942:Receptors, Adrenergic, alpha / Q000235:genetics*; D014158:Transcription, Genetic
D005938:Glucocorticoids; D012739:Gonadal Steroid Hormones; D012333:RNA, Messenger; D011942:Receptors, Adrenergic, alpha; D003907:Dexamethasone; D003513:Cycloheximide