Enhanced oxidative stress in GH-transgenic rat and acromegaly in humans

• Published in: Growth hormone & IGF research 2012-04, Vol.22 (2), p.64-68
• Main Authors: Nishizawa, Hitoshi, Handayaningsih, Anastasia-Evi, Iguchi, Genzo, Cho, Yoshitake, Takahashi, Michiko, Yamamoto, Masaaki, Suda, Kentaro, Kasahara, Kohei, Hakuno, Fumihiko, Yamanouchi, Keitaro, Nishihara, Masugi, Seino, Susumu, Takahashi, Shin-Ichiro, Takahashi, Yutaka
• Format: Article
• Language: English
• Subjects: Acromegaly; Acromegaly - metabolism; Advanced Basic Science; Animals; Animals, Genetically Modified; Dose-Response Relationship, Drug; Endocrinology & Metabolism; Female; GH-transgenic rat; Growth Hormone - genetics; Growth Hormone - metabolism; Humans; IGF-I; Insulin-Like Growth Factor I - metabolism; Male; Mice; Muscle Cells - cytology; Oxidative Stress; Oxygen - chemistry; Prevalence; Rats; Reactive Oxygen Species; ROS
• ISSN: 1096-6374; 1532-2238
• DOI: 10.1016/j.ghir.2012.02.001

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 and methods 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.