Estrogen augments glucose transporter and IGF1 expression in primate cerebral cortex

Abstract

Estrogen has many positive effects on neural tissue in experimental model systems, including stimulation of neurite growth and neurotransmitter synthesis and protection against diverse types of neural injury. In humans, estrogen treatment is reputed to protect against Alzheimer's disease. To investigate potential mediators of estrogen's action and determine whether selective estrogen receptor modulators (SERMs) such as tamoxifen have estrogen‐like effects in the primate brain, we evaluated the expression of glucose transporters and insulin‐like growth factor 1 (IGF1) and its receptor in the frontal cortex of ovariectomized rhesus monkeys. We treated one group for 3 days with vehicle, another with 17β estradiol (E2), and a third with tamoxifen. The expression of facilitative glucose transporters (Gluts) 1, 3, and 4 was investigated using in situ hybridization, immunohistochemistry, and immunoblot analysis. Gluts 3 and 4 were concentrated in cortical neurons and Glut1 in capillaries and glial cells. E2 treatment induced two‐ to fourfold increases in Glut3 and Glut4 mRNA levels and lesser but significant increases in Glut3 and 4 protein levels. E2 treatment induced an ~70% increase in parenchymal Glut1 mRNA levels, but did not appreciably affect vascular Glut1 gene expression. IGF1 and IGF1 receptor mRNAs were concentrated in cortical neurons in a distribution similar to Gluts 3 and 4. IGF1 mRNA levels were significantly increased in E2‐treated animals but IGF1 receptor mRNA levels were not altered by hormone treatment. Tamoxifen increased cerebral cortical Glut3 and 4 mRNA levels, but did not affect Glut1, IGF1, or IGF1 receptor expression. This study provides novel data showing that Gluts 3 and 4 and IGF1 are coexpressed by primate cerebral cortical neurons, where their expression is enhanced by estrogen. These findings suggest that up‐regulation of glucose transporter and IGF1 expression may contribute to estrogen's salutary effects on neural tissue. Tamoxifen, an antiestrogen at the breast, is shown to have estrogenlike effects on higher brain centers in the monkey, suggesting that some SERMs may share estrogen's neuroprotective potential for menopausal women.— Cheng, C., Cohen, M., Wang, J., Bondy, C. Estrogen augments glucose transporter and IGF1 expression in primate cerebral cortex. FASEB J. 15, 907–915 (2001)

Women's higher brain metabolic rate compensates for early Alzheimer's pathology

“…Estrogen is known to enhance brain metabolism and blood flow 33–35 . Primate studies show that estradiol increases glucose transporter and insuline‐like growth factor 1 (IGF1) expression in the frontal cortex 36 . In vivo studies demonstrate estradiol modulation of glucose transporter 1 (GLUT‐1) protein and messenger RNA (mRNA) expression in blood‐brain barrier endothelium 37 .…”

Comparison of near‐infrared fluorescent deoxyglucose probes with different dyes for tumor diagnosis in vivo

“…The GLUT1 expression on the different cancer cells were found to decrease in the following order: MCF-7/estradiol > MDA-MB-435 > U87MG > MCF-7. Because estrogen was reported to increase the GLUT1 expression in MCF-7 cancer cells and accelerate the tumor growth in mice (26)(27)(28), MCF-7 cancer cells with estradiol treatment were also investigated to confirm the influence of estradiol on the GLUT1 expression. Grayscale analysis ( Fig.…”

Non‐genomic mechanisms in the estrogen regulation of glycolytic protein levels in endothelial cells

“…The glucose transporter GLUT1 is the first rate‐limiting step in glucose utilization in tissues that rely on glycolysis as a source of energy, 35 such as the brain, and is the most abundant isoform in endothelial cells 36 . In addition, in vivo data demonstrate that E2 regulates GLUT1 levels at transcriptional or posttranscriptional levels 15,37 . However, the effect of E2 or selective ER agonists on endothelial GLUT1 levels has not been assessed yet.…”