Hypothalamic neuronal histamine signaling in the estrogen deficiency-induced obesity.
Menopause is one of the triggers that induce obesity. Estradiol (E2), corticotropin-releasing hormone (CRH), and hypothalamic neuronal histamine are anorexigenic substances within the hypothalamus. This study examined the interactions among E2, CRH, and histamine during the regulation of feeding behavior and obesity in rodents. Food intake was measured in rats after the treatment of E2, alpha-fluoromethyl histidine, a specific suicide inhibitor of histidine decarboxylase that depletes hypothalamic neuronal histamine, or CRH antagonist. We measured food intake and body weight in wild-type mice or mice with targeted disruption of the histamine receptors (H1-R) knockout (H1KO mice). Furthermore, we investigated CRH content and histamine turnover in the hypothalamus after the E2 treatment or ovariectomy (OVX). We used immunohistochemical staining for estrogen receptors (ERs) in the histamine neurons. The E2-induced suppression of feeding was partially attenuated in rats pre-treated with alpha-fluoromethyl histidine or CRH antagonist and in H1KO mice. E2 treatment increased CRH content and histamine turnover in the hypothalamus. OVX increased food intake and body weight, and decreased CRH content and histamine turnover in the hypothalamus. In addition, E2 replacement reversed the OVX-induced changes in food intake and body weight in wild-type mice but not in H1KO mice. Immunohistochemical analysis revealed ERs were expressed on histamine neurons and western blotting analysis and pre-absorption study confirmed the specificity of ER antiserum we used. These results indicate that CRH and hypothalamic neuronal histamine mediate the suppressive effects of E2 on feeding behavior and body weight.
Gotoh
Koro
K
Department of Internal Medicine 1, Faculty of Medicine, Oita University, Hasama, Yufu, Japan.
Masaki
Takayuki
T
Chiba
Seiichi
S
Higuchi
Keiko
K
Kakuma
Tetsuya
T
Shimizu
Hiroyuki
H
Mori
Masatomo
M
Sakata
Toshiie
T
Yoshimatsu
Hironobu
H
D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D004195:Disease Models, Animal; D004347:Drug Interactions; D004435:Eating / Q000187:drug effects / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D006632:Histamine / Q000378:metabolism*; D008762:Methylhistidines / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009765:Obesity / Q000139:chemically induced / Q000473:pathology*; D010052:Ovariectomy / Q000379:methods; D010286:Paraventricular Hypothalamic Nucleus / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000378:metabolism; D011969:Receptors, Histamine H1 / Q000172:deficiency; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D004791:Enzyme Inhibitors; D004967:Estrogens; D008762:Methylhistidines; D011960:Receptors, Estrogen; D011969:Receptors, Histamine H1; D004958:Estradiol; C028309:alpha-fluoromethylhistidine; D006632:Histamine; D003346:Corticotropin-Releasing Hormone