Affordable Access

Attenuation by reactive oxygen species of glucocorticoid suppression on proopiomelanocortin gene expression in pituitary corticotroph cells.

Authors
  • Asaba, Koichi
  • Iwasaki, Yasumasa
  • Yoshida, Masanori
  • Asai, Masato
  • Oiso, Yutaka
  • Murohara, Toyoaki
  • Hashimoto, Kozo
Type
Published Article
Journal
Endocrinology
Publication Date
Jan 01, 2004
Volume
145
Issue
1
Pages
39–42
Identifiers
PMID: 14576191
Source
Medline
License
Unknown

Abstract

Up-regulation of hypothalamo-pituitary-adrenal axis is maintained during acute inflammation and/or infection, in the face of sustained elevation of plasma glucocorticoid hormone. Inflammatory stress is usually associated with high plasma cytokine levels and increased generation of reactive oxygen species (ROS) as well. In this study, we examined the effect of ROS on the negative feedback regulation of glucocorticoid in hypothalamo-pituitary-adrenal axis using AtT20 corticotroph cells in vitro. When the cells were treated with H2O2, glucocorticoid suppression on the proopiomelanocortin gene promoter activity was attenuated in a dose-dependent manner. H2O2 also inhibited the ligand-stimulated nuclear translocation of glucocorticoid receptor. The released glucocorticoid suppression by H2O2 was not observed when the cells were cotreated with antioxidants. Together, these results suggest that increased ROS generation in the oxidative redox state attenuates the glucocorticoid negative feedback system, at least in part, by interfering with the nuclear translocation of glucocorticoid receptor and eliminating the repression on proopiomelanocortin gene expression.

Report this publication

Statistics

Seen <100 times