Metabolism of parathyroid hormone by fetal rat calvaria.

These studies examine the metabolism of highly purified bovine parathyroid hormone [bPTH-(1--84)] by fetal rat calvaria. Enzymatically dispersed bone cells and intact (minced) calvaria were incubated with bPTH-(1--84) and the incubation medium was analyzed for degradation of PTH by polyacrylamide gel electrophoresis. Eluates of gel slices were assayed for immunoreactive PTH (iPTH) in carboxy- and amino-terminal RIAs. Both bone preparations metabolized bPTH-(1--84). The intact hormone progessively decreased with time and carboxy-terminal iPTH fragments were evident by 5 min of incubation. In the isolated cell preparations, intact hormone was completely degraded at submaximal doses of PTH (5 X 10(-9) M), as assessed by cAMP production. Degradation was incomplete in intact calvarial preparations at all doses studied. Intact calvaria were less sensitive to PTH with regard to cAMP production. No amino-terminal fragments were detected in the medium with either cell preparation. Oxidized (biologically inactive) bPTH-(1--84) was not metabolized in these systems. These findings contrast with studies in liver and kidney preparations, where oxidized bPTH has been shown to be degraded. These findings contrast with studies in liver and kidney preparations, where oxidized bPTH has been shown to be degraded. These data suggest that biological activity may be necessary for the metabolism of intact bPTH-(1--84) by bone cells and that skeletal tissue may contribute to the immunoheterogeneity of circulating PTH in the rat.