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乳腺上皮细胞中葡萄糖转运蛋白1(GLUT1)的高表达和极化表达:断奶对GLUT1载体的急性下调作用

High and polarized expression of GLUT1 glucose transporters in epithelial cells from mammary gland: acute down-regulation of GLUT1 carriers by weaning.

作者信息

Camps M, Vilaro S, Testar X, Palacín M, Zorzano A

机构信息

Departament de Bioquímica i Fisiologia, Facultat de Biologia, Universitat de Barcelona, Spain.

出版信息

Endocrinology. 1994 Feb;134(2):924-34. doi: 10.1210/endo.134.2.8299587.

Abstract

During lactation, the mammary gland shows high metabolic activity, which is dependent at least in part on the availability of glucose. We have studied the regulation of glucose transporter expression in different types of cell in rat mammary gland during the reproductive cycle. Glucose transporter expression varied markedly in the mammary gland during ontogeny. Thus, GLUT1 protein expression increased progressively during pregnancy, reaching the highest levels during lactation. A peak of lactation, GLUT1 protein content, expressed per g issue, was greater in mammary gland than in GLUT1-enriched tissues such as rat brain. In contrast, GLUT4 showed a marked decrease during pregnancy and practically disappeared during lactation. Regardless of the developmental stage, GLUT4 was expressed in adipocytes but not in epithelial cells from mammary gland. On the other hand, GLUT1 was expressed in both cell types. The overall pattern of GLUT1 and GLUT4 expression during the reproductive cycle reflects differences in the cell composition of the mammary gland. Thus, whereas adipocytes predominate before pregnancy, epithelial cells are the main cell type in the mammary gland during late pregnancy and lactation. Immunofluorescence and immunoelectron microscopy indicated that GLUT1 was essentially localized to the basolateral domain of epithelial cells in the mammary gland at peak of lactation, and hardly any labeling was found in the luminal membrane of epithelial cells. GLUT1 expression was acutely regulated in epithelial cells from mammary gland. Thus, GLUT1 protein markedly decreased in lactating rats 24 h after abrupt weaning in the presence of a moderate decrease in GLUT1 mRNA levels. The effect of weaning on GLUT1 protein content was not due to the fall in the plasma concentration of PRL. Thus, bromocriptine treatment for 24 h decreased GLUT1 mRNA levels in the mammary gland, but did not alter the content of GLUT1 protein. Our results demonstrate 1) the existence of a high and polarized expression of GLUT1 glucose transporters in epithelial cells from mammary gland, and 2) that GLUT1 expression is acutely regulated at a posttranslational level by weaning; this is not mimicked by bromocriptine treatment, which rules out PRL as the regulatory factor involved in the effect.

摘要

在哺乳期,乳腺表现出高代谢活性,这至少部分依赖于葡萄糖的可利用性。我们研究了大鼠乳腺在生殖周期中不同类型细胞中葡萄糖转运蛋白表达的调控。在个体发育过程中,乳腺中葡萄糖转运蛋白的表达有显著变化。因此,葡萄糖转运蛋白1(GLUT1)的蛋白表达在怀孕期间逐渐增加,在哺乳期达到最高水平。在泌乳高峰期,以每克组织计算,乳腺中GLUT1蛋白含量高于富含GLUT1的组织,如大鼠脑。相反,葡萄糖转运蛋白4(GLUT4)在怀孕期间显著减少,在哺乳期几乎消失。无论发育阶段如何,GLUT4在脂肪细胞中表达,但在乳腺上皮细胞中不表达。另一方面,GLUT1在这两种细胞类型中均有表达。生殖周期中GLUT1和GLUT4表达的总体模式反映了乳腺细胞组成的差异。因此,在怀孕前脂肪细胞占主导,而在怀孕后期和哺乳期上皮细胞是乳腺中的主要细胞类型。免疫荧光和免疫电子显微镜显示,在泌乳高峰期,GLUT1主要定位于乳腺上皮细胞的基底外侧结构域,在上皮细胞的腔膜中几乎没有发现标记。乳腺上皮细胞中GLUT1的表达受到急性调控。因此,在突然断奶24小时后,泌乳大鼠中的GLUT1蛋白显著减少,同时GLUT1 mRNA水平有适度下降。断奶对GLUT1蛋白含量的影响不是由于催乳素(PRL)血浆浓度的下降。因此,用溴隐亭处理24小时可降低乳腺中GLUT1 mRNA水平,但不改变GLUT1蛋白含量。我们的结果表明:1)乳腺上皮细胞中存在GLUT1葡萄糖转运蛋白的高表达和极化表达;2)GLUT1的表达在翻译后水平受到断奶的急性调控;溴隐亭处理不能模拟这种调控,这排除了PRL作为参与该效应的调节因子。

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