17β-Estradiol transcriptionally represses human insulin receptor gene expression causing cellular insulin resistance

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• 作者：Garcí ; a-Arencibia ; Moisé ; s ; Molero ; Susana ; Dá ; vila ; Norma ; Carmen Carranza ; M. ; et. al.
• 关键词：E₂ ; 17&#946 ; -estradiol ; IR ; insulin receptor ; PI3-kinase ; phosphatidylinositol 3-kinase ; ER ; estrogen receptor ; ERα ; estrogen receptor alpha ; ER&#946 ; estrogen receptor beta ; ERE ; estrogen response element ; 17&#946 ; -Estradiol ; Human insul
• 刊名：Leukemia Research
• 出版年：2005
• 出版时间：January, 2005
• 年：2005
• 卷：29
• 期：1
• 页码：79-87
• 全文大小：295 K

文摘

In this study, we demonstrate that 17β-estradiol (E₂) inhibits human insulin receptor (IR) gene expression in a dose- and time-dependent manner in U-937 human promonocytic cells. Using cells transfected with the −1819 to −271bp fragment of the human IR promoter (wild type promoter) and treated with E₂, we show that this repression is regulated at the transcriptional level. The steroid was also found to diminish the insulin responsiveness of the cells in terms of cell survival, DNA synthesis, glucose transport, and glucose oxidation, this last effect possibly involving reduced phosphatidylinositol 3-kinase (PI3-kinase) activity. These data provide new information on the molecular mechanisms of estrogen-inducing insulin resistance in human cells.