Examination of the requirement for metabolism of parathyroid hormone in skeletal tissue before biological action.

Abstract

Previous studies have suggested that parathyroid hormone (1–84), the predominent glandular and secreted form of parathyroid hormone (PTH), might be cleaved to an active fragment before exerting its hormonal effect in target tissues. It was subsequently established that this form of the hormone is active without the requirement for proteolysis in stimulating adenylate cyclase in renal tissue. The present studies were undertaken to examine the necessity for cleavage of PTH (1–84) in the other major target tissue (bone) and thereby to determine if a tissue-specific enzyme might confer target organ specificity upon the PTH molecule. Unlabeled or 125I-labeled bovine PTH (1–84) was incubated for 10 min at 22 C or 37 C with fetal rabbit calvarial tissue, and the incubation mixtures were analyzed by gel filtration and gel electrophoresis. RIA, using antisera directed against the NH2- and COOHtermini, were employed for the detection of unlabeled hormone. Analysis of the metabolic fate of the hormone was correlated...