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.