Glucocorticoids increase NPY gene expression in the arcuate nucleus by inhibiting mTOR signaling in rat hypothalamic organotypic cultures.
The mammalian target of rapamycin (mTOR) has been implicated in the regulation of physiological functions such as cell growth and proliferation, and glucocorticoids reportedly inhibit mTOR signaling in peripheral tissues. Recent studies suggest that the mTOR signaling in the hypothalamus plays a critical role in maintaining energy homeostasis. In this study, we examined whether the mTOR signaling in the hypothalamus is involved in the regulation of neuropeptide Y (Npy) gene expression in the arcuate nucleus by glucocorticoids. In the hypothalamic organotypic cultures, the incubation with rapamycin significantly inhibited the mTOR signaling which was shown by decreases in the levels of phosphorylated p70S6K1 and S6. Similar to the action of the mTOR inhibitor rapamycin, dexamethasone (DEX), a synthetic glucocorticoid, also inhibited the mTOR signaling in the hypothalamic explants. Analyses of the explants with in situ hybridization demonstrated that the DEX or rapamycin alone significantly increased Npy gene expression in the arcuate nucleus, but that there were no additive effects of DEX and rapamycin on the expression. These data suggest that glucocorticoids upregulate the Npy gene expression in the arcuate nucleus by inhibiting mTOR signaling, at least in part.
Shimizu
Hiroshi
H
Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
Arima
Hiroshi
H
Ozawa
Yoshiharu
Y
Watanabe
Minemori
M
Banno
Ryoichi
R
Sugimura
Yoshihisa
Y
Ozaki
Nobuaki
N
Nagasaki
Hiroshi
H
Oiso
Yutaka
Y
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D003907:Dexamethasone / Q000378:metabolism / Q000494:pharmacology; D005938:Glucocorticoids / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007031:Hypothalamus / Q000033:anatomy & histology* / Q000187:drug effects / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases; D046509:Tissue Culture Techniques
D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D047908:Intracellular Signaling Peptides and Proteins; D009478:Neuropeptide Y; D012333:RNA, Messenger; D003907:Dexamethasone; C546842:MTOR protein, human; C546845:mTOR protein, rat; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus