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首页> 外文期刊>Neuroendocrinology: International Journal for Basic and Clinical Studies on Neuroendocrine Relationships >Effects of hormones targeting nuclear receptors on transcriptional regulation of the growth hormone gene in the MtT/S rat somatotrope cell line.
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Effects of hormones targeting nuclear receptors on transcriptional regulation of the growth hormone gene in the MtT/S rat somatotrope cell line.

机译：靶向核受体的激素对MtT / S大鼠体细胞细胞系中生长激素基因转录调控的影响。

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摘要

We have examined the effects of nuclear receptor hormones such as glucocorticoid, gonadal steroid hormones, thyroid hormone and retinoids on the transcriptional regulation of the 5'-promoter activity of growth hormone (GH) gene using the MtT/S rat pure somatotrope cell line or MtT/SGL, a subclone of MtT/S in which the rat GH gene 5'-promoter (1.7 Kb)-luciferase fusion gene was stably incorporated. RT-PCR analyses revealed that receptors for all the hormones except androgen receptor were expressed in the cell line. Triiodothyronine (T(3), 10 nM) transiently but significantly stimulated the promoter activity of GH gene, whereas retinoic acids (9-cis and all-trans, both 1 microM) showed sustained stimulation. There were no additive effects among the T(3), all-trans, and9-cis retinoic acids. Synthetic glucocorticoid hormone dexamethasone (100 nM) showed an inhibitory effect but, interestingly, significantly enhanced T(3)-stimulated GH promoter activity during long-term incubation. Among the gonadal steroidhormones tested, estradiol and estriol had significant stimulatory effects, and deletion analysis showed that the estrogen effect was maintained with the shortest construct examined (-150 to +6, +1 denotes the transcription start site). These results suggest that thyroid hormone and retinoids stimulate the transcription of GH gene, probably through a common response element, whereas glucocorticoid has both negative and positive effects on GH expression, depending on the combination with other hormones and the time of exposure. Estrogens also have direct stimulatory effects through the proximal promoter region of GH gene.
机译：我们已经使用MtT / S大鼠纯种生长激素细胞系或MtT / S研究了核受体激素（如糖皮质激素，性腺甾体激素，甲状腺激素和类维生素A）对生长激素（GH）基因5'-启动子活性的转录调控的作用。 MtT / SGL，MtT / S的亚克隆，其中大鼠GH基因5'-启动子（1.7 Kb）-萤光素酶融合基因被稳定整合。 RT-PCR分析显示，除雄激素受体外，所有激素的受体均在细胞系中表达。 Triiodothyronine（T（3），10 nM）短暂但显着刺激了GH基因的启动子活性，而视黄酸（9-顺式和全反式，均为1 microM）显示出持续的刺激作用。 T（3），全反式和9-顺式视黄酸之间没有累加效应。合成的糖皮质激素激素地塞米松（100 nM）表现出抑制作用，但有趣的是，在长期孵育过程中，T（3）刺激的GH启动子活性显着增强。在所测试的性腺类固醇激素中，雌二醇和雌三醇具有显着的刺激作用，缺失分析表明，在检测到的最短构建体下，雌激素作用得以维持（-150至+ 6，+ 1表示转录起始位点）。这些结果表明，甲状腺激素和类维生素A可能通过共同的应答元件刺激GH基因的转录，而糖皮质激素对GH的表达既有正面影响又有负面影响，这取决于与其他激素的组合和暴露时间。雌激素还通过GH基因的近端启动子区域具有直接刺激作用。

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