title: Similar changes of hypothalamic feeding-regulating peptides mRNAs and plasma leptin levels in PTHrP-, LIF-secreting tumors-induced cachectic rats and adjuvant arthritic rats.
abstract: Parathyroid hormone-related protein (PTHrP) is a causative factor of humoral hypercalcemia in malignancy. However, it is difficult to explain the mechanism of anorexia/cachexia with PTHrP secretion in detail. Previously, we demonstrated that the expressions of orexigenic peptides increased and anorexigenic peptides decreased under cachectic conditions in rats carrying tumors secreting PTHrP. In this study, we investigated whether such changes in the expression of hypothalamic feeding-regulating peptides can be solely attributed to PTHrP or are a general response under cachectic conditions. Cachectic syndromes were induced in rats by: (i) inoculation of human lung cancer LC-6 cells that secreted PTHrP, (ii) inoculation of human melanoma SEKI cells that secrete not PTHrP but LIF1, (iii) injection of heat-killed Mycobacterium leading to arthritis (AA) and (iv) oral administration of a high dose of 1α,25(OH)(2)D(3) that resulted in hypercalcemia. The LC-6-bearing rats and AA rats were treated with or without anti-PTHrP antibody and indomethacin, respectively, and the expression of the hypothalamic feeding-regulating peptide mRNAs were examined by in situ hybridization histochemistry. The orexigenic peptide mRNAs, such as neuropeptide Y and agouti-related protein, were significantly increased, and that of anorexigenic peptide mRNAs, such as proopiomelanocortin, cocaine- and amphetamine-regulated transcript and corticotropin-releasing hormone were significantly decreased when they developed cachectic syndromes and AA. A high dose of 1α,25(OH)(2)D(3) caused hypercalcemia and body weight loss but did not affect the expression of hypothalamic feeding-regulating peptide mRNAs. The expressions of the hypothalamic feeding-regulating peptides change commonly in different chronic cachectic models without relating to serum calcium levels.
authors.affiliation: Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hashimoto
authors.forename: Makoto
authors.initials: M
authors.lastname: Kawasaki
authors.forename: Miho
authors.initials: M
authors.lastname: Watanabe
authors.forename: Hiroki
authors.initials: H
authors.lastname: Otsubo
authors.forename: Toru
authors.initials: T
authors.lastname: Ishikura
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Fujihara
authors.forename: Hideo
authors.initials: H
authors.lastname: Ohnishi
authors.forename: Etsuro
authors.initials: E
authors.lastname: Onuma
authors.forename: Hisafumi
authors.initials: H
authors.lastname: Yamada-Okabe
authors.forename: Yoh
authors.initials: Y
authors.lastname: Takuwa
authors.forename: Etsuro
authors.initials: E
authors.lastname: Ogata
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nakamura
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ueta
mesh_terms: D054369:Agouti-Related Protein / Q000096:biosynthesis; D000818:Animals; D001169:Arthritis, Experimental / Q000150:complications / Q000378:metabolism*; D002100:Cachexia / Q000378:metabolism*; D045744:Cell Line, Tumor; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis; D006801:Humans; D006934:Hypercalcemia / Q000209:etiology; D007031:Hypothalamus / Q000378:metabolism*; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D020738:Leptin / Q000097:blood*; D053605:Leukemia Inhibitory Factor / Q000378:metabolism*; D008297:Male; D009374:Neoplasms, Experimental / Q000150:complications / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009478:Neuropeptide Y / Q000096:biosynthesis; D009479:Neuropeptides / Q000096:biosynthesis; D000068797:Orexins; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011923:Rats, Nude; D017208:Rats, Wistar; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D054369:Agouti-Related Protein; D047908:Intracellular Signaling Peptides and Proteins; C507837:LIF protein, human; D020738:Leptin; D053605:Leukemia Inhibitory Factor; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D009479:Neuropeptides; D000068797:Orexins; D044162:Parathyroid Hormone-Related Protein; D012333:RNA, Messenger; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D011333:Pro-Opiomelanocortin; D003346:Corticotropin-Releasing Hormone