Estradiol reduces nonclassical transcription at cyclic adenosine 3',5'-monophosphate response elements in glioma cells expressing estrogen receptor alpha.

Abstract

Estradiol can protect the brain from a variety of insults by activating membrane-initiated signaling pathways, and thereby modulate gene expression and lead to functional changes in neurons. These direct neuronal effects of the hormone have been well documented; however, it is less understood what effects estradiol may have on nonneuronal cells of the central nervous system. There is evidence that estradiol levels can induce the release of glial-derived growth factors and other cytokines, suggesting that estradiol may both directly and indirectly protect neurons. To determine whether 17beta-estradiol (E2) can activate rapid signaling and modulate nonclassical transcription in astrocytes, we stably transfected the C6 rat glioblastoma cell line with human estrogen receptor (ER) alpha (C6ERalpha) or rat ERbeta (C6ERbeta). Introduction of a cAMP response element-luciferase reporter gene into C6, C6ERalpha, and C6ERbeta cells leads to the observation that E2 treatment reduced isoproterenol-stimulated luciferase activity by 35% in C6ERalpha but had no effect on reporter gene expression in C6ERbeta or untransfected C6 cells. A similar effect was seen with a membrane-impermeable estrogen (E2-BSA), suggesting the modulation of nonclassical transcription by estradiol treatment is mediated by the activation of a membrane-initiated signaling pathway. Furthermore, pretreatment with wortmannin (phosphatidylinsositol 3-kinase) or U73122 (phospholipase C) attenuated the E2-induced reduction in nonclassical transcription. We conclude that E2 treatment reduces cAMP response element-mediated transcription in glioma cells expressing ERalpha and that this reduction is dependent on the activation of membrane-initiated signaling. These findings suggest a novel model of estrogen rapid signaling in astrocytes that leads to modulation of nonclassical transcription.

• Authors: Andrew J Mhyre, Robert A Shapiro, Daniel M Dorsa
• Journal: Endocrinology (Endocrinology) Vol. 147 Issue 4 Pg. 1796-804 (Apr 2006) ISSN: 0013-7227 [Print] United States
• PMID: 16439453 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Estrogen Receptor alpha
• Estradiol
• Cyclic AMP
• Phosphatidylinositol 3-Kinases
• Type C Phospholipases

Topics

• Animals
• Cell Line, Tumor
• Cyclic AMP (physiology)
• Estradiol (pharmacology)
• Estrogen Receptor alpha (physiology)
• Glioma (metabolism)
• Phosphatidylinositol 3-Kinases (physiology)
• Rats
• Response Elements (physiology)
• Signal Transduction (drug effects)
• Transcription, Genetic (drug effects)
• Type C Phospholipases (physiology)