title: The synthetic human parathyroid hormone-related protein is inhibited by a parathyroid hormone antagonist in rats in vivo.
abstract: The structure of a novel protein, parathyroid hormone-related protein (PTHrP), secreted by human tumors associated with hypercalcemia has recently been determined. Administration of a synthetic fragment of this protein in vivo reproduces features of the clinical paraneoplastic syndrome of humoral hypercalcemia of malignancy and produces biologic responses closely similar to those obtained with parathyroid hormone (PTH). A PTH antagonist designed to reversibly occupy PTH receptors inhibited major actions of the tumor peptide in vivo, including phosphaturia, urinary cAMP excretion, and increased serum ionized calcium. These studies indicate that PTHrP and PTH mediate their bioactivities through shared receptors in vivo and establish a potential specific mechanism-based approach utilizing PTH antagonists for the therapy of tumor-associated hypercalcemia.
authors.affiliation: Division of Endocrinology, Cedars-Sinai Medical Center/UCLA 90048.
authors.forename: N
authors.initials: N
authors.lastname: Horiuchi
authors.forename: T
authors.initials: T
authors.lastname: Hongo
authors.forename: T L
authors.initials: TL
authors.lastname: Clemens
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001681:Biological Assay; D002118:Calcium / Q000097:blood; D000242:Cyclic AMP / Q000652:urine; D006801:Humans; D008969:Molecular Sequence Data; D010281:Parathyroid Hormone / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000494:pharmacology*; D010710:Phosphates / Q000652:urine; D011506:Proteins / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: C470121:PTHLH protein, human; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D010710:Phosphates; D011506:Proteins; C038040:parathyroid hormone (7-34)amide, Tyr(34)-; D000242:Cyclic AMP; D002118:Calcium