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非洲爪蟾肝脏中白蛋白基因表达的转录后调控:雌激素受体依赖性机制的证据。

Posttranscriptional regulation of albumin gene expression in Xenopus liver: evidence for an estrogen receptor-dependent mechanism.

作者信息

Riegel A T, Aitken S C, Martin M B, Schoenberg D R

机构信息

Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799.

出版信息

Mol Endocrinol. 1987 Feb;1(2):160-7. doi: 10.1210/mend-1-2-160.

Abstract

We have previously shown that estrogen administration to male Xenopus laevis results in the posttranscriptional suppression of serum albumin mRNA concurrent with the transcriptional activation of the genes for the yolk protein precursor vitellogenin. To determine whether the posttranscriptional regulation of albumin gene expression is mediated through a mechanism involving the high affinity estrogen receptor protein or through a receptor-independent mechanism involving a middle affinity cytoplasmic estrogen-binding protein we examined the effects of the competitive estrogen receptor antagonist 4-hydroxytamoxifen. Administration of 4-hydroxytamoxifen 24 h before estradiol completely blocked both the suppression of albumin mRNA and the transcriptional activation of the vitellogenin genes. Albumin gene transcription remained constitutive under all treatment regimens. Competitive binding experiments demonstrated that 4-hydroxytamoxifen has an affinity for the estrogen receptor similar to that of estradiol. However, 4-hydroxytamoxifen displays little or no interaction with the middle affinity cytoplasmic estrogen-binding protein. These data indicate that the estrogen receptor occupies a key role in the posttranscriptional regulation of albumin mRNA.

摘要

我们之前已经表明,给雄性非洲爪蟾施用雌激素会导致血清白蛋白mRNA的转录后抑制,同时伴随着卵黄蛋白前体卵黄生成素基因的转录激活。为了确定白蛋白基因表达的转录后调控是通过涉及高亲和力雌激素受体蛋白的机制介导的,还是通过涉及中等亲和力细胞质雌激素结合蛋白的非受体依赖机制介导的,我们研究了竞争性雌激素受体拮抗剂4-羟基他莫昔芬的作用。在雌二醇给药前24小时给予4-羟基他莫昔芬,完全阻断了白蛋白mRNA的抑制和卵黄生成素基因的转录激活。在所有治疗方案下,白蛋白基因转录保持组成性。竞争性结合实验表明,4-羟基他莫昔芬对雌激素受体的亲和力与雌二醇相似。然而,4-羟基他莫昔芬与中等亲和力细胞质雌激素结合蛋白几乎没有或没有相互作用。这些数据表明,雌激素受体在白蛋白mRNA的转录后调控中起关键作用。

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