Attenuation by reactive oxygen species of glucocorticoid suppression on proopiomelanocortin gene expression in pituitary corticotroph cells.
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.
Asaba
Koichi
K
Department of Clinical Pathophysiology, Nagoya University Graduate School of Medicine and Hospital, Nagoya 466-8550, Japan.
Iwasaki
Yasumasa
Y
Yoshida
Masanori
M
Asai
Masato
M
Oiso
Yutaka
Y
Murohara
Toyoaki
T
Hashimoto
Kozo
K
D000324:Adrenocorticotropic Hormone / Q000235:genetics; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D025461:Feedback, Physiological / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D016877:Oxidants / Q000494:pharmacology; D010902:Pituitary Gland / Q000166:cytology*; D011333:Pro-Opiomelanocortin / Q000235:genetics*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
D005938:Glucocorticoids; D008070:Lipopolysaccharides; D016877:Oxidants; D017382:Reactive Oxygen Species; D011333:Pro-Opiomelanocortin; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D006861:Hydrogen Peroxide