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Effects of oxidation of human parathyroid hormone on its biological activity in continuously infused, thyroparathyroidectomized rats
Author(s) -
Horiuchi Noboru
Publication year - 1988
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650030316
Subject(s) - parathyroid hormone , endocrinology , medicine , chemistry , calcium , hydrogen peroxide , metabolism , vitamin , hormone , methionine sulfoxide , vitamin d and neurology , urine , calcium metabolism , in vivo , methionine , amino acid , biochemistry , biology , microbiology and biotechnology
The effect of oxidation of human parathyroid hormone 1–34 (hPTH 1–34) on the hormone's biological activity was assessed in vivo using a multiparameter, thyroparathyroidectomized (TPTX) rat model. The peptide was oxidized by treatment with hydrogen peroxide, and the oxidized form (8,18‐methionine sulfoxide) was isolated by reverse‐phase HPLC. Vitamin D‐deficienf rats were infused with either intact or oxidized hormone along with a 5 m M calcium chloride solution for 4 or 18 hr. Infusion of nonoxidized hormone (0.1–0.8 nmoles/hr) resulted in dose‐dependent increases in serum calcium, decreases in serum phosphate, decreases in urine calcium, increases in urine phosphate and cAMP, and increased renal 1,25‐dihydroxyvitamin D 3 (1,25 (OH) 2 D 3 ) production. Oxidized PTH infused at doses up to 0.8 nmole/hr had no effect on any of these parameters. To assess the effect of oxidation on the ability of PTH to inhibit the production of the 24,25‐dihydroxyvitamin D 3 (24,25(OH) 2 D 3 ), the infusion protocol was performed in vitamin D‐deficient rats repleted with 1,25(OH) 2 D 3 by injection. In these experiments, intact hormone markedly suppressed 24,25(OH) 2 D 3 production, whereas the oxidized form was without effect. We conclude that intact methionine residues at positions 8 and 18 of hPTH 1–34 are necessary for all its major biological actions, including its effect on the renal metabolism of 25‐hydroxyvitamin D 3 (25(OH)D 3 ).