Sakaue M, Hoffman B B
Department of Medicine, Stanford University School of Medicine, Palo Alto, California.
J Clin Invest. 1991 Aug;88(2):385-9. doi: 10.1172/JCI115315.
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.
类固醇激素通过多种机制调节生理过程，包括基因表达调控。我们想知道糖皮质激素是否可能诱导α1肾上腺素能受体的表达，这可能导致血管平滑肌对儿茶酚胺的敏感性增加，而这种情况可能在糖皮质激素过量时发生。我们研究了地塞米松对DDT1 MF - 2平滑肌细胞中α1B肾上腺素能受体基因表达的影响。用地塞米松（10^(-6) M）处理后，用[3H]哌唑嗪测定的α1B受体表达增加了1.8±0.2倍。通过Northern印迹分析，α1B肾上腺素能受体mRNA的稳态值在暴露于地塞米松48小时后增加了2.8±0.7倍。地塞米松的这种作用在存在蛋白质合成抑制剂环己酰亚胺的情况下也会发生。睾酮和醛固酮也能增加α1B受体mRNA的丰度，而β-雌二醇和孕酮则没有作用。在核转录分析中测定的α1B受体基因转录率，在用地塞米松处理24小时的细胞中增加了2.6±0.6倍。地塞米松对α1B受体mRNA的半衰期没有影响。这些数据表明，糖皮质激素通过增加该基因的转录速率来调节α1B受体的表达。
