Title: 17β-Estradiol transcriptionally represses human insulin receptor gene expression causing cellular insulin resistance
Authors: García-Arencibia, Moisés 
Molero, Susana
Dávila, Norma
Carmen Carranza, M.
Calle, Consuelo
UNESCO Clasification: 2302 Bioquímica
320507 Neurología
Keywords: 17β-Estradiol
Human insulin receptor gene
Transcriptional repression
Insulin resistance
Cell survival
DNA synthesis
Glucose transport
Glucose oxidation
U-937 cells
Issue Date: 2005
Publisher: 0145-2126
Journal: Leukemia Research 
Abstract: 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 −271 bp 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.
URI: http://hdl.handle.net/10553/43016
ISSN: 0145-2126
DOI: 10.1016/j.leukres.2004.05.012
Source: Leukemia Research[ISSN 0145-2126],v. 29, p. 79-87
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