Direct in vitro evidence of extracellular Ca2+-induced amino-terminal truncation of human parathyroid hormone (1-84) by human parathyroid cells

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Abstract

Context: Although serum calcium (Ca2+) concentration regulates the generation of amino-terminally (N-terminally) truncated forms of human PTH (hPTH) degraded from (1-84)hPTH, no studies have yet reported whether the parathyroid gland itself is responsible for this process. Objective: Our objective was to determine the site of N-terminal truncation and its roles in PTH metabolism in parathyroid cells in vitro. Methods: The effect of extracellular Ca2+ concentration was examined on N-terminal truncation in primary cultured parathyroid cells. The parathyroid glands were obtained from the patients with primary and uremia-associated secondary hyperparathyroidisms who underwent therapeutic parathyroidectomies. Results: The N-terminally truncated fragments were detectable with commercially available intact PTH (I-PTH) assays, but not with the bio-intact PTH (Bio-PTH) assay, which detected only the (1-84)hPTH. HPLC revealed that generation of N-terminally truncated fragments detectable by I-PTH increased with extracellular Ca2+ concentration. Suppression of PTH secretion by increasing the extracellular Ca2+ concentration was more evident with the Bio-PTH assay than with the I-PTH assay for both cultured parathyroid cells prepared from parathyroid adenomas and uremia-associated secondary hyperparathyroidism. The Bio-PTH/I-PTH ratio, which is the ratio of (1-84)hPTH to the sum of (1-84)hPTH and N-terminally truncated fragments, decreased in response to increases in extracellular Ca2+. Conclusions: These findings suggest that the N-terminal truncation is regulated by extracellular Ca2+ concentration and works to suppress the generation of (1-84)hPTH in parathyroid cells. Copyright © 2005 by The Endocrine Society.

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Kawata, T., Imanishi, Y., Kobayashi, K., Onoda, N., Takemoto, Y., Tahara, H., … Nishizawa, Y. (2005). Direct in vitro evidence of extracellular Ca2+-induced amino-terminal truncation of human parathyroid hormone (1-84) by human parathyroid cells. Journal of Clinical Endocrinology and Metabolism, 90(10), 5774–5778. https://doi.org/10.1210/jc.2005-0243

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