Glucocorticoids induce transcription and expression of the alpha 1B adrenergic receptor gene in DTT1 MF-2 smooth muscle cells.

Glucocorticoids induce transcription and expression of the alpha 1B adrenergic receptor gene in DTT1 MF-2 smooth muscle cells.
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糖皮质激素诱导 DTT1 MF-2 平滑肌细胞中 α 1B 肾上腺素受体基因的转录和表达。

DOI:
10.1172/jci115315
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发表时间:
1991
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
Hoffman,BB
Hoffman,BB
中科院分区:
--
文献类型:
--
作者:
Sakaue,M;Hoffman,BB

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类固醇激素通过包括基因表达调控在内的多种机制调节生理过程。我们想知道糖皮质激素是否可能诱导α 1肾上腺素能受体的表达,这可能有助于血管平滑肌对儿茶酚胺的敏感性增加,这可能与糖皮质激素过量有关。我们检测了地塞米松对DDT1 MF-2平滑肌细胞α 1B肾上腺素能受体基因表达的影响。地塞米松(10(-6)M)使α 1B受体表达增加1.8 +/- 0.2倍,[3H]吡唑嗪测定。通过Northern blotting分析α 1B肾上腺素能受体mRNA的稳态值,暴露于地塞米松48小时后增加2.8 +/- 0.7倍。地塞米松的这种作用发生在蛋白质合成抑制剂环己亚胺存在的情况下。睾酮和醛固酮也增加了α 1B受体mRNA的丰度,而雌二醇和孕酮对α 1B受体mRNA的丰度没有影响。通过核径流测定,α 1B受体基因转录率在地塞米松处理24小时的细胞中增加了2.6 +/- 0.6倍。α 1B受体mRNA的半衰期在地塞米松作用下没有变化。这些数据表明,糖皮质激素通过增加α 1B基因的转录率来调节α 1B受体的表达。图片
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.Images