title: Enhanced oxidative stress in GH-transgenic rat and acromegaly in humans.
abstract: BACKGROUND
  Excessive oxidative stress plays a causal role in various diseases such as diabetes, hypertension, atherosclerosis, and heart failure. Acromegaly is a pathological condition associated with excess growth hormone (GH) and insulin-like growth factor-I (IGF-I) and a high prevalence of diabetes, hypertension, atherosclerosis, and heart failure; resulting in premature death. We hypothesized that these conditions may be associated with increased oxidative stress.
  
  
  OBJECTIVE
  We explored the oxidative stress levels in the serum and tissues of GH-transgenic rats as an animal model for acromegaly. We also measured the oxidative stress levels in the serum of patients with acromegaly and age-, sex-, and BMI-matched control subjects. We examined the effects of GH and IGF-I on reactive oxygen species (ROS) production in C2C12 myocytes.
  
  
  RESULTS
  The levels of an oxidative stress marker, serum thiobarbituric acid reactive substances (TBARS) were increased in the GH-transgenic rats. Further, tissue oxidative stress damage was enhanced in the cardiomyocytes and vascular smooth muscle cells in the aorta of the GH-transgenic rats. In addition, serum TBARS levels and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were increased in acromegaly in humans. IGF-I but not GH induced ROS production in C2C12 myocytes in vitro.
  
  
  CONCLUSIONS
  These data indicate that the increased levels of IGF-I are associated with enhanced oxidative stress in rats and humans. In addition, increased ROS may play an important role in the complications and premature death in acromegaly.
authors.affiliation: Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nishizawa
authors.forename: Anastasia-Evi
authors.initials: AE
authors.lastname: Handayaningsih
authors.forename: Genzo
authors.initials: G
authors.lastname: Iguchi
authors.forename: Yoshitake
authors.initials: Y
authors.lastname: Cho
authors.forename: Michiko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Masaaki
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Kentaro
authors.initials: K
authors.lastname: Suda
authors.forename: Kohei
authors.initials: K
authors.lastname: Kasahara
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Hakuno
authors.forename: Keitaro
authors.initials: K
authors.lastname: Yamanouchi
authors.forename: Masugi
authors.initials: M
authors.lastname: Nishihara
authors.forename: Susumu
authors.initials: S
authors.lastname: Seino
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Takahashi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Takahashi
mesh_terms: D000172:Acromegaly / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D004305:Dose-Response Relationship, Drug; D005260:Female; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D051379:Mice; D032342:Muscle Cells / Q000166:cytology; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry; D015995:Prevalence; D051381:Rats; D017382:Reactive Oxygen Species
chemical_list: D017382:Reactive Oxygen Species; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D010100:Oxygen