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.