Parathyroid hormone-related protein has an anorexigenic activity via activation of hypothalamic urocortins 2 and 3.
Cancer cachexia is reported to be a major cause of cancer-related death. Since the pathogenesis is not entirely understood, only few effective therapies have been established. Since myriad tumors produce parathyroid hormone-related protein (PTHrP), plasma concentrations of PTHrP are increased in cancer cachexia. We measured the food intake, gastric emptying, conditioned taste aversion (CTA), and gene expression of hypothalamic neuropeptides in mice after administering PTHrP intraperitoneally. We administered PTHrP intravenously in rats and examined the gastroduodenal motility and vagal nerve activities. We also examined whether chronic administration of PTHrP influenced the food intake and body weight. Peripherally administered PTHrP induced negative energy balance by decreasing the food intake and gastric emptying; however, it did not induce CTA. The mechanism involved the activation of hypothalamic urocortins 2 and 3 through vagal afferent pathways and the suppression of gastroduodenal motor activity. The continuous infusion of PTHrP reduced the food intake and body weight gain with a concomitant decrease in the fat and skeletal muscle. Our findings suggest that PTHrP influences the food intake and body weight; therefore, PTHrP can be considered as a therapeutic target for cancer cachexia.
Asakawa
Akihiro
A
Department of Social and Behavioral Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Sakuragaoka, Kagoshima, Japan.
Fujimiya
Mineko
M
Niijima
Akira
A
Fujino
Kazunori
K
Kodama
Noriko
N
Sato
Yuki
Y
Kato
Ikuo
I
Nanba
Hiroaki
H
Laviano
Alessandro
A
Meguid
Michael M
MM
Inui
Akio
A
D000818:Animals; D000855:Anorexia / Q000139:chemically induced* / Q000378:metabolism; D001067:Appetite Depressants / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D004435:Eating / Q000187:drug effects; D005746:Gastric Emptying / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D057967:Infusions, Intraventricular; D008297:Male; D051379:Mice; D044162:Parathyroid Hormone-Related Protein / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D054832:Urocortins / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D015430:Weight Gain / Q000187:drug effects
D001067:Appetite Depressants; D044162:Parathyroid Hormone-Related Protein; D054832:Urocortins