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This version published online on October 23, 2003
Endocrinology, doi:10.1210/en.2003-0375
A more recent version of this article appeared on January 1, 2004
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Submitted on March 26, 2003
Accepted on October 3, 2003

Attenuation by Reactive Oxygen Species of Glucocorticoid Suppression on Proopiomelanocortin Gene Expression in Pituitary Corticotroph Cells

KOICHI ASA BA,1, YASUMASA IWASAKI1*, MASANORI YOSHIDA1, MASATO ASAI1, YUTAKA OISO1, TOYOAKI MUROHARA1, and KOZO HASHIMOTO1

1 Departments of Clinical Pathophysiology (K.A., Y.I.) and Internal Medicine (M.Y., M.A., Y.O., T.M.), Nagoya University Graduate School of Medicine and Hospital, Nagoya 466-8560; Second Department of Internal Medicine (K.A., K.H.), Kochi Medical School, Nankoku, Kochi 783-8505, Japan

* To whom correspondence should be addressed. E-mail: iwasakiy{at}med.nagoya-u.ac.jp.

Up-regulation of hypothalamo-pituitary-adrenal (HPA) 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 HPA axis using AtT20 corticotroph cells in vitro. When the cells were treated with H2O2, glucocorticoid suppression on the proopiomelanocortin (POMC) 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 co-treated 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 GR and eliminating the repression on POMC gene expression.
Key words: proopiomelanocortin • glucocorticoid • redox • reactive oxygen species Abbreviated title: ROS and POMC Negative Feedback Regulation






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