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

In this study, we demonstrate that 17β-estradiol (E 2) 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 wit...

Full description

Saved in:
Bibliographic Details
Published in:Leukemia research 2005, Vol.29 (1), p.79-87
Main Authors: Garcı́a-Arencibia, Moisés, Molero, Susana, Dávila, Norma, Carmen Carranza, M., Calle, Consuelo
Format: Article
Language:English
Subjects:
17β-Estradiol
Cell survival
DNA synthesis
Glucose oxidation
Glucose transport
Human insulin receptor gene
Insulin resistance
Transcriptional repression
U-937 cells
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:In this study, we demonstrate that 17β-estradiol (E 2) 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 E 2, 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.
ISSN:0145-2126
1873-5835
DOI:10.1016/j.leukres.2004.05.012