title: Corticosterone Inhibits the Proliferation of C6 Glioma Cells via the Translocation of Unphosphorylated Glucocorticoid Receptor.
abstract: Astroglial cells have been considered to have passive brain function by helping to maintain neurons. However, recent studies have revealed that the dysfunction of such passive functions may be associated with various neuropathological diseases, such as schizophrenia, Alzheimer's disease, amyotrophic lateral sclerosis and major depression. Corticosterone (CORT), which is often referred to as the stress hormone, is a well-known regulator of peripheral immune responses and also shows anti-inflammatory properties in the brain. However, it is still obscure how CORT affects astroglial cell function. In this study, we investigated the effects of CORT on the proliferation and survival of astroglial cells using C6 glioma cells. Under treatment with CORT for 24h, the proliferation of C6 glioma cells decreased in a dose-dependent manner. Moreover, this inhibition was diminised by treatment with mifepristone, a glucocorticoid receptor (GR) antagonist, but not by spironolactone, a mineralocorticoid receptor (MR) antagonist, and was independent of GR phosphorylation and other GR-related intracellular signaling cascades. Furthermore, it was observed that the translocation of GR from the cytosol to the nucleus was promoted by the treatment with CORT. These results indicate that CORT decreases the proliferation of C6 glioma cells by modifying the transcription of a particular gene related to cell proliferation independent of GR phosphorylation.
authors.affiliation: Department of Pharmacology, School of Pharmacy, International University of Health and Welfare.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Nakatani
authors.forename: Taku
authors.initials: T
authors.lastname: Amano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeda
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003345:Corticosterone / Q000494:pharmacology*; D005910:Glioma / Q000378:metabolism; D006727:Hormone Antagonists / Q000494:pharmacology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D015735:Mifepristone / Q000494:pharmacology; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D013148:Spironolactone / Q000494:pharmacology
chemical_list: D006727:Hormone Antagonists; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D015735:Mifepristone; D003345:Corticosterone