Endocrinology, Vol 122, 2098-2102, Copyright © 1988 by Endocrine Society

ARTICLES

Inhibition of in vitro bone resorption by a parathyroid hormone receptor antagonist in the canine adenocarcinoma model of humoral hypercalcemia of malignancy

TJ Rosol and CC Capen
Department of Veterinary Pathobiology, Ohio State University, Columbus 43210.

In vitro bone resorption induced by tumor extract derived from a hypercalcemic canine adenocarcinoma was significantly inhibited by the PTH receptor antagonist, [Nle8,18,Tyr34]bovine (b) PTH-(3-34) amide. Dose-response curves were prepared for in vitro bone resorption induced in neonatal mouse calvaria by tumor extract, bPTH-(1-34), and prostaglandin E2. A 1:2000-fold ratio of bPTH-(1-34) to [Nle8,18,Tyr34]bPTH-(3-34) amide significantly inhibited bone resorption induced by bPTH-(1-34); however, a 1:10,000 ratio completely antagonized bone resorption. At equivalent potency (1.80-fold stimulation of in vitro bone resorption) of tumor extract compared to bPTH-(1-34), [Nle8,18,Tyr34]bPTH-(3-34) amide (5.0 microM) was capable of significantly reducing in vitro bone resorption. Bone resorption induced by tumor extract (1.35-fold stimulation) was inhibited by [Nle8,18,Tyr34]bPTH-(3-34) amide at concentrations of 5.0 and 1.0 microM. Bone resorption induced by prostaglandin E2 (300 nM) was not inhibited by [Nle8,18,Tyr34]bPTH-(3-34) amide (5.0 microM). These data indicate that [Nle8,18,Tyr34]bPTH-(3-34) amide antagonizes in vitro bone resorption induced by bPTH-(1-34) in a dose-dependent manner and significantly inhibits bone resorption induced by the canine adenocarcinoma model of humoral hypercalcemia of malignancy.