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Examination of the Requirement for Metabolism of Parathyroid Hormone in Skeletal Tissue before Biological Action^*

The Department of Medicine, McGill University, and the Royal Victoria Hospital Montreal, Canada

The author is the recipient of a scholarship from the medical research council of Canada. Requests for reprints should be addressed to: Dr. D. Goltzman, Department of Experimental Medicine, Strathcona Medical Building Room 2-11, 3640 University Street, Montreal, Canada, H3A 2B2.

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 with the capacity to stimulate adenylate cyclase. That fraction of the hormone bound to tissue was also analyzed by immunochemical means and by bioassay after fractionation by gel chromatography. The results demonstrate that the 84-amino acid form of PTH is capable of activating adenylate cyclase in skeletal tissue in vitro without prior cleavage. Thus, metabolism of PTH does not appear to be a necessary requirement for biological activity (adenylate cyclase stimulation) in either major target tissue. (Endocrinology 102: 1555, 1978)

Footnotes

^* This work was supported by Grants MA-5775 and MA-5860 from the Medical Research Council of Canada and by Grant 760012 from the Quebec Medical Research Council.

Received August 22, 1977.

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