title: Effect of dihydrotestosterone on mouse embryonic stem cells exposed to H2O2-induced oxidative stress.
abstract: Oxidative stresses induced by reactive oxygen species (ROS) have been shown to be involved in several physiological and pathophysiological processes, such as cell proliferation and differentiation. Steroid hormones can protect cells against apoptosis or induce cell proliferation by several mechanisms. Among androgenic hormones, dihydrotestosterone (DHT) is generated by a 5alpha- reduction of testosterone. Unlike testosterone, DHT cannot be aromatized to estradiol, therefore DHT is considered a pure androgenic steroid. This study was conducted to examine the effect of DHT (10(-7) M) on H2O2 (10(-3) M) -induced injuries in mouse embryonic stem (ES) cells. H2O2 induced ROS generation and increased lipid peroxide formation and DNA fragmentation. These effects of H2O2 were inhibited by pretreatment with DHT. H2O2 also increased the phosphorylation of p38 MAPK, SAPK/JNK and nuclear factor kappa B (NF-kappaB), but DHT blocked these effects. Moreover, H2O2 decreased DNA synthesis and the levels of cell cycle regulatory proteins [cyclin D1, cyclin E, cyclin-dependent kinase (CDK) 2, and CDK 4]. These effects of H2O2 were inhibited by pretreatment with DHT. In conclusion, DHT may partially prevent H2O2-induced cell injury through inhibition of ROS and ROS-induced activation of p38 MAPK, SAPK/JNK and NF-kappaB in mouse ES cells.
authors: Department of Urology, Chonnam National University Medical School, Gwangju 501-746, Korea.
authors: Mi Na
authors: MN
authors: Lee
authors: Sang Hun
authors: SH
authors: Lee
authors: Min Young
authors: MY
authors: Lee
authors: Yun Hee
authors: YH
authors: Kim
authors: Jae Hong
authors: JH
authors: Park
authors: Jung Min
authors: JM
authors: Ryu
authors: Seung Pil
authors: SP
authors: Yun
authors: Yu Jin
authors: YJ
authors: Lee
authors: Mi Ok
authors: MO
authors: Kim
authors: Kwangsung
authors: K
authors: Park
authors: Ho Jae
authors: HJ
authors: Han
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000494:pharmacology*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*; D004789:Enzyme Activation; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D051379:Mice; D008954:Models, Biological; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013936:Thymidine / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D017382:Reactive Oxygen Species; D013196:Dihydrotestosterone; D006861:Hydrogen Peroxide; D048051:p38 Mitogen-Activated Protein Kinases; D013936:Thymidine