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, p<0.05). Unexpectedly, NPY
mRNA levels in CRH-Tg were significantly decreased at 14 weeks old (WT: 1571.5±111.2, CRH-Tg: 949.1±139.3 dpm/mg, p<0.05), and there were no differences in
POMC mRNA levels between CRH-Tg and WT. On the other hand, AgRP
mRNA levels in CRH-Tg were significantly increased compared with WT at both ages (14w old: WT 365.6±88.6, CRH-Tg 660.1±87.2 dpm/ mg, p<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.