Calcium-dependent intracellular degradation of parathyroid hormone: a possible mechanism for the regulation of hormone stores.
The dynamics of parathyroid hormone (PTH) biosynthesis, storage, and secretion in bovine parathyroid slices in vitro in response to alterations in the concentrations of extracellular calcium were studied. Hormone biosynthesis was evaluated by using polyacrylamide gel electrophoresis to measure incorporation of [3H]leucine into newly synthesized PTH and proparathyroid hormone (ProPTH) during short (35 min) incubations. Amounts of newly synthesized PTH stored in and secreted from the tissue slices were determined by electrophoretic analysis of [3H]PTH in extracts of tissue and media. Total PTH and ProPTH is slices and media were measured by specific radioimmunoassays. PTH secretion rates changes 5-fold when calcium was lowered from 2mM to 1mM. Secretion of some PTH continued despite high concentrations of calcium (5 mM). Biosynthesis of ProPTH was changed only slightly, and conversion of ProPTH to PTH was independent of the extracellular calcium concentration. Tissue stores of PTH increased during incubation of parathyroid slices in medium containing high amounts of calcium. The increase in stores was much less, however, than predicted by the findings of marked suppression of secretion and little change in rates of PTH biosynthesis. In high concentrations of calcium, a large fraction (up to 50%) of newly synthesized PTH was degraded within the tissue, whereas in low concentrations of calcium, little (less than 10%) of the PTH was degraded. No fragments of PTH or ProPTH were identified in either extracts of tissue or media, suggesting that degradation occurred rapidly by general proteolysis rather than by limited, specific endopeptidase activity. The data suggest that the parathyroid cell contains a calcium-sensitive degradative pathway for PTH and that this pathway may be involved in the regulation of hormone production and secretion.
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002417:Cattle; D004591:Electrophoresis, Polyacrylamide Gel; D066298:In Vitro Techniques; D007930:Leucine / Q000378:metabolism; D010280:Parathyroid Glands / Q000187:drug effects / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D011498:Protein Precursors / Q000096:biosynthesis / Q000276:immunology; D011863:Radioimmunoassay; D013997:Time Factors
D010281:Parathyroid Hormone; D011498:Protein Precursors; D007930:Leucine; D002118:Calcium