Corticotropin-releasing hormone (CRH) transgenic mice display hyperphagia with increased Agouti-related protein mRNA in the hypothalamic arcuate nucleus

Endocrine Journal

Takafumi Taguchi¹  Masayuki Shinahara¹  Masayuki Tsuda²  Shuichi Nakayama¹  Kozo Hashimoto¹  Yoshio Terada¹  Shinya Makino¹  Mizuho Okazaki¹  Mitsuru Nishiyama¹  Yasumasa Iwasaki¹  Mary P Stenzel-Poore³  Yasushi Okada²  Makoto Tsugita¹ 

[1] Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, Nankoku, Japan;Department of Laboratory Animal Science, Kochi Medical School, Kochi University, Nankoku, Japan;Department of Molecular Microbiology and Immunology, Oregon Health Science University, Portland, USA

关键词: Cushing’s syndrome;    Appetite;    Obesity;    Glucocorticoid;    Agouti-related protein;   

DOI  :  10.1507/endocrj.K10E-370

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(36)Cited-By(7)Although glucocorticoid-induced hyperphagia is observed in the patients with glucocorticoid treatment or Cushing’s syndrome, its molecular mechanism is not clear.We thus explored the expression of neuropeptide mRNAs in the hypothalamus related to appetite regulation in CRH over-expressing transgenic mice (CRH-Tg), a model of Cushing’s syndrome.We measured food intake, body weight (including body fat weight) and plasma corticosterone levels in CRH-Tg and their wild-type littermates (WT) at 6 and 14 weeks old.We also examined neuropeptide Y (NPY), proopiomelanocortin (POMC) and Agouti-related protein (AgRP) mRNAs in the arcuate nucleus (ARC) using in situ hybridization.Circulating corticosterone levels in CRH-Tg were markedly elevated at both 6 and 14 weeks old.Body fat weight in CRH-Tg was significantly increased at 14 weeks old, which is considered as an effect of chronic glucocorticoid excess.At both 6 and 14 weeks old, CRH-Tg mice showed significant hyperphagia compared with WT (14w old: WT 3.9±0.1, CRH-Tg 5.1±0.7 g/day, ppp<0.05).These results suggest that glucocorticoid-induced hyperphagia is associated with increased hypothalamic AgRP.Our results also indicate that hypothalamic NPY does not have an essential role in the increased food intake during glucocorticoid excess.

【 授权许可】

Unknown