Glucocorticoid receptors in cultured human skin fibroblasts: evidence for down-regulation of receptor by glucocorticoid hormone.
Glucocorticoid receptors in cultured human skin fibroblasts: evidence for down-regulation of receptor by glucocorticoid hormone.
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DOI：
10.2340/0001555567461468
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发表时间：
1987-11
影响因子：
3.6
通讯作者：
A. Oikarinen;H. Oikarinen;C. Meeker;E. Tan;J. Uitto
中科院分区：
文献类型：
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作者：
A. Oikarinen;H. Oikarinen;C. Meeker;E. Tan;J. Uitto
在本研究中，我们确定了特定的糖皮质激素受体在培养的人皮肤成纤维细胞与[3 H]地塞米松作为配体。采用全细胞测定法确定成纤维细胞培养物中糖皮质激素受体密度和结合亲和力，该培养物来自16名健康对照受试者、4名活动性进行性系统性硬化症（PSS）患者、3名疤痕疙瘩患者和3名糖尿病患者。PSS、瘢痕疙瘩、糖尿病和对照成纤维细胞中的受体密度在相同范围内，值分别为6.3 +/-4.9，7.7 +/-3.6，5.3 +/-1.3和7.9 +/-6.2 fmol/微克DNA（平均值+/- SD）。在进一步的研究中，在测定受体之前，将细胞与10（-7）M地塞米松孵育4或9天。[3 H]地塞米松在类固醇处理的文化中的特异性结合是在对照中观察到的62%和13%，表明下调。相反，用10（-5）M全反式维甲酸孵育成纤维细胞并没有改变[3 H]地塞米松的结合，表明在受体水平缺乏药理学干扰。
In the present study, we have determined the specific glucocorticoid receptors in cultured human skin fibroblasts with [3H]dexamethasone as the ligand. The whole-cell assay was employed for determination of glucocorticoid receptor densities and binding affinities in fibroblast cultures established either from 16 healthy control subjects, from 4 patients with active progressive systemic sclerosis (PSS), from 3 patients with keloids and 3 patients with diabetes mellitus. The receptor densities in PSS, keloid, diabetes and control fibroblasts were in the same range, the values being 6.3 +/- 4.9, 7.7 +/- 3.6, 5.3 +/- 1.3 and 7.9 +/- 6.2 fmol/micrograms DNA (mean +/- SD), respectively. In further studies, the cells were incubated with 10(-7) M dexamethasone for 4 or 9 days before the receptors were assayed. The specific binding of [3H]dexamethasone in steroid treated cultures was 62 and 13% of that observed in controls, suggesting down-regulation. In contrast, incubation of fibroblasts with 10(-5) M all-trans-retinoic acid did not alter the binding of [3H]dexamethasone, suggesting lack of pharmacologic interference at the receptor level.