Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1975 Jul;56(1):39–48. doi: 10.1172/JCI108077

Metabolism in immunoreactive parathyroid hormone in the dog. The role of the kidney and the effects of chronic renal disease.

K A Hruska, R Kopelman, W E Rutherford, S Klahr, E Slatopolsky, A Greenwalt, T Bascom, J Markham
PMCID: PMC436553  PMID: 1141439

Abstract

The role of the kidney in the metabolism of parathyroid hormone (PTH) was examined in the dog. Studies were performed in awake normal and uremic dogs after administration of bovine parathyroid hormone (b-PTH) or synthetic amino terminal tetratricontapeptide of b-PTH (syn b-PTH 1-34). The renal clearance of immunoreactive PTH was determined from the product of renal plasma flow and the percent extraction of PTH immunoreactivity by the kidney. Blood levels of circulating immunoreactive PTH were determined by radioimmunoassay. The normal dog kidney extracted 20 plus or minus 1% of the immunoreactive b-PTH delivered to it, and renal clearance (RC) of immunoreactivity was 60 ml/min. When RC was compared to an estimate of total metabolic clearance (MCR) of immunoreactivity, it accounted for 61% of the total. Both MCR and RC were markedly decreased in dogs with chronic renal disease. However, the percent extraction of immunoreactive PTH was unchanged in chronic renal disease, and the observed decrease in RC was due to changes in renal plasma flow. The largest portion of the reduction in total MCR was accounted for by the decrease in RC, and there was no compensation for the decrease in RC by extrarenal sites of PTH metabolism.

Full text

PDF
45

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arnaud C. D., Tsao H. S., Littledike T. Radioimmunoassay of human parathyroid hormone in serum. J Clin Invest. 1971 Jan;50(1):21–34. doi: 10.1172/JCI106476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aurbach G. D., Keutmann H. T., Niall H. D., Tregear G. W., O'Riordan J. L., Marcus R., Marx S. J., Potts J. T., Jr Structure, synthesis, and mechanism of action of parathyroid hormone. Recent Prog Horm Res. 1972;28:353–398. [PubMed] [Google Scholar]
  3. BERMAN M., SHAHN E., WEISS M. F. The routine fitting of kinetic data to models: a mathematical formalism for digital computers. Biophys J. 1962 May;2:275–287. doi: 10.1016/s0006-3495(62)86855-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. BRICKER N. S., KLAHR S., RIESELBACH R. E. THE FUNCTIONAL ADAPTATION OF THE DISEASED KIDNEY. I. GLOMERULAR FILTRATION RATE. J Clin Invest. 1964 Oct;43:1915–1921. doi: 10.1172/JCI105065. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Berson S. A., Yalow R. S. Immunochemical heterogeneity of parathyroid hormone in plasma. J Clin Endocrinol Metab. 1968 Jul;28(7):1037–1047. doi: 10.1210/jcem-28-7-1037. [DOI] [PubMed] [Google Scholar]
  6. Canterbury J. M., Levey G. S., Reiss E. Activation of renal cortical adenylate cyclase by circulating immunoreactive parathyroid hormone fragments. J Clin Invest. 1973 Feb;52(2):524–527. doi: 10.1172/JCI107211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Canterbury J. M., Reiss E. Multiple immunoreactive molecular forms of parathyroid hormone in human serum. 1. Proc Soc Exp Biol Med. 1972 Sep;140(4):1393–1398. doi: 10.3181/00379727-140-36681. [DOI] [PubMed] [Google Scholar]
  8. Coburn J. W., Koppel M. H., Brickman A. S., Massry S. G. Study of intestinal absorption of calcium in patients with renal failure. Kidney Int. 1973 Apr;3(4):264–272. doi: 10.1038/ki.1973.40. [DOI] [PubMed] [Google Scholar]
  9. Fang V. S., Tashjian A. H., Jr Studies on the role of the liver in the metabolism of parathyroid hormone. I. Effects of partial hepatectomy and incubation of the hormone with tissue homogenates. Endocrinology. 1972 May;90(5):1177–1184. doi: 10.1210/endo-90-5-1177. [DOI] [PubMed] [Google Scholar]
  10. GREENWOOD F. C., HUNTER W. M., GLOVER J. S. THE PREPARATION OF I-131-LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC RADIOACTIVITY. Biochem J. 1963 Oct;89:114–123. doi: 10.1042/bj0890114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. HARVEY R. B., BROTHERS A. J. Renal extraction of para-aminohippurate and creatinine measured by continuous in vivo sampling of arterial and renal-vein blood. Ann N Y Acad Sci. 1962 Oct 31;102:46–54. doi: 10.1111/j.1749-6632.1962.tb13624.x. [DOI] [PubMed] [Google Scholar]
  12. Habener J. F., Segre G. V., Powell D., Murray T. M., Potts J. T., Jr Immunoreactive parathyroid hormone in circulation of man. Nat New Biol. 1972 Aug 2;238(83):152–154. doi: 10.1038/newbio238152a0. [DOI] [PubMed] [Google Scholar]
  13. Herbert V., Lau K. S., Gottlieb C. W., Bleicher S. J. Coated charcoal immunoassay of insulin. J Clin Endocrinol Metab. 1965 Oct;25(10):1375–1384. doi: 10.1210/jcem-25-10-1375. [DOI] [PubMed] [Google Scholar]
  14. Hurst R. O. A simplified approach to the use of determinants in the calculation of the rat equation for a complex enzyme system. Can J Biochem. 1967 Dec;45(12):2015–2039. doi: 10.1139/o67-235. [DOI] [PubMed] [Google Scholar]
  15. Kraml M. A semi-automated determination of phospholipids. Clin Chim Acta. 1966 Apr;13(4):442–448. doi: 10.1016/0009-8981(66)90235-x. [DOI] [PubMed] [Google Scholar]
  16. Martin T. J., Melick R. A., de Luise M. Metabolism of parathyroid hormone. Degradation of 125I-labelled hormone by a kidney enzyme. Biochem J. 1969 Feb;111(4):509–514. doi: 10.1042/bj1110509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Melick R. A., Martin T. J. Parathyroid hormone metabolism in man: effect of nephrectomy. Clin Sci. 1969 Dec;37(3):667–674. [PubMed] [Google Scholar]
  18. ORIMO H., FUJITA T., MORII H., NAKAO K. INACTIVATION IN VITRO OF PARATHYROID HORMONE ACTIVITY BY KIDNEY SLICES. Endocrinology. 1965 Feb;76:255–258. doi: 10.1210/endo-76-2-255. [DOI] [PubMed] [Google Scholar]
  19. Reis E., Canterbury J. M. A radioimmunoassay for parathyroid hormone in man. Proc Soc Exp Biol Med. 1968 Jun;128(2):501–504. doi: 10.3181/00379727-128-33050. [DOI] [PubMed] [Google Scholar]
  20. Segre G. V., Niall H. D., Habener J. F., Potts J. T., Jr Metabolism of parathyroid hormone: physiologic and clinical significance. Am J Med. 1974 Jun;56(6):774–784. doi: 10.1016/0002-9343(74)90805-5. [DOI] [PubMed] [Google Scholar]
  21. Silverman R., Yalow R. S. Heterogeneity of parathyroid hormone. Clinical and physiologic implications. J Clin Invest. 1973 Aug;52(8):1958–1971. doi: 10.1172/JCI107380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Slatopolsky E., Caglar S., Gradowska L., Canterbury J., Reiss E., Bricker N. S. On the prevention of secondary hyperparathyroidism in experimental chronic renal disease using "proportional reduction" of dietary phosphorus intake. Kidney Int. 1972 Sep;2(3):147–151. doi: 10.1038/ki.1972.84. [DOI] [PubMed] [Google Scholar]
  23. Slatopolsky E., Caglar S., Pennell J. P., Taggart D. D., Canterbury J. M., Reiss E., Bricker N. S. On the pathogenesis of hyperparathyroidism in chronic experimental renal insufficiency in the dog. J Clin Invest. 1971 Mar;50(3):492–499. doi: 10.1172/JCI106517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. TAIT J. F. REVIEW: THE USE OF ISOTOPIC STEROIDS FOR THE MEASUREMENT OF PRODUCTION RATES IN VIVO. J Clin Endocrinol Metab. 1963 Dec;23:1285–1297. doi: 10.1210/jcem-23-12-1285. [DOI] [PubMed] [Google Scholar]
  25. Yalow R. S., Berson S. A. Purification of 131-I parathyroid hormone with microfine granules of precipitated silica. Nature. 1966 Oct 22;212(5060):357–358. doi: 10.1038/212357a0. [DOI] [PubMed] [Google Scholar]
  26. Zull J. E., Repke D. W. The tissue localization of tritiated parathyroid hormone in thyroparathyroidectomized rats. J Biol Chem. 1972 Apr 10;247(7):2195–2199. [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES