Maintenance of normocalcemia by continuous infusion of the synthetic bovine parathyroid hormone (1–34) in parathyroidectomized rats
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This work was conducted to estimate the replacement dose of the synthetic bovine parathyroid hormone [PTH(1–34)] that is required for maintenance of serum calcium (Ca) in parathyroidectomized (PTX) rats. Male rats were PTX and used in this study only if serum Ca was reduced to at least 7 mg/dl. We found that a solution of 2% cysteine, 150 mM NaCl, and 1 mM HCl was superior to 20 mM acetic acid for maintenance of biological activity of PTH (1–34) in situ during the period of hormone infusion studied. The PTH dose—calcemic response relationship was investigated using PTH in doses of 0.6, 1, and 3 U/h. The infusion of 1 U PTH per hour raised Ca to the normal level, whereas rats infused with 0.6 U/h were hypocalcemic and 3 U/h resulted in marked hypercalcemia. To extend this observation we carried out an infusion of 1 U PTH per hour for 14 days. We found that this infusion rate of bovine PTH (1–34) provided a relatively stable level of serum calcium with modest fluctuation from normocalcemic to somewhat hypercalcemic levels for the entire 14-day period of PTH infusion. Serum calcitonin was also elevated during the infusion period and then returned to the initial level when PTH treatment was stopped. After the minipumps containing PTH were removed, the serum Ca dropped rapidly to 5 mg/dl, which was significantly lower than the control (vehicle-infused) or initial values of serum Ca (7 mg/dl). Infusion of PTH at 3 U/h for 4 days did not produce this rebound hypocalcemia after the pumps were removed. Serum Ca in those experiments returned to the initial level after hormone treatment was discontinued.
Key wordsSerum calcium Parathyroidectomized rat Parathyroid hormone
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- 4.Obie JF, Cooper CW (1979) Loss of calcemic effects of calcitonin and parathyroid hormone infused continuously into rats using the Alzet osmotic minipump. J Pharmac Exp Ther 209:422–428Google Scholar
- 7.Snedecor GW, Cochran WG (1967) Statistical Methods, 6th ed. Iowa State University Press, Ames, p 59Google Scholar
- 8.Nickols GA, Carnes DL, Anast CS, Forte LR (1979) Parathyroid hormone-mediated refractoriness of rat kidney cyclic AMP system. Am J Physiol 236:E-401–E-409Google Scholar
- 10.DiBella FP, Arnaud CD, Brewer HB Jr (1976) Relative biologic activities of human and bovine parathyroid hormones and their synthetic NH2-terminal (1–34) peptides, as evaluatedin vitro with renal cortical adenylate cyclase obtained from three different species. Endocrinology 99:429–436Google Scholar
- 11.Herrmann-Erlee MPM, van der Meer JM, Hekkelman JW (1980)In vitro studies of the adenosine 3′,5′-monophosphate (cAMP) response of embryonic rat calvaria to bovine parathyroid hormone-(1–84) (b PTH-(1–84)), bPTH-(1–34), and bPTH-(3–34) and the loss of cAMP responsiveness after prolonged incubation. Endocrinology 106:2013–2018PubMedGoogle Scholar