The synthetic human parathyroid hormone‐related protein is inhibited by a parathyroid hormone antagonist in rats in vivo

Noboru Horiuchi, Takashi Hongo, Thomas L. Clemens

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)541-545
Number of pages5
JournalJournal of Bone and Mineral Research
Volume5
Issue number6
DOIs
StatePublished - Jun 1990
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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