[PTHrP and cancer cachexia].

Parathyroid hormone-related peptide (PTHrP) was discovered to be a causative factor of humoral hypercalcemia of malignancy (HHM) . It also causes cachexia including reduced food intake, body weight loss, and decreased locomotor activity by a mechanism that is independent of hypercalcemia and proinflammatory cytokine actions. PTHrP-induced cachexia is not associated with the repression of orexigenic peptides or induction of anorexigenic peptides ; unexpectedly, the expression of orexigenic peptides was increased and that of anorexigenic peptides was decreased in animals that developed PTHrP-induced cachexia. A neutralizing antibody against PTHrP rapidly restored food intake, body weight, and locomotor activity and also normalized the expression of orexigenic and anorexigenic peptides. Thus, PTHrP induces cachexia by mechanisms other than directly affecting the hypothalamic feeding regulated peptides.