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. 1981 Mar;67(3):885–892. doi: 10.1172/JCI110106

Peripheral Metabolism of Intact Parathyroid Hormone

ROLE OF LIVER AND KIDNEY AND THE EFFECT OF CHRONIC RENAL FAILURE

K A Hruska 1, A Korkor 1, K Martin 1, E Slatopolsky 1
PMCID: PMC370640  PMID: 7204561

Abstract

The plasma disappearance rate (metabolic clearance rate) of administered intact parathyroid hormone (intact PTH) was analyzed in awake dogs with indwelling hepatic and renal vein catheters. The metabolic clearance rate (MCR) of intact PTH was found to be very rapid, 21.6 ± 3.1 ml/min per kg in 11 normal dogs. The liver accounted for the greatest fraction of the MCR of intact PTH (61 ± 4%) by virtue of an arterial minus venous (a - v) difference across the liver of 45 ± 3%. The renal uptake of intact PTH accounted for 31 ± 3% of the MCR of intact PTH. The renal a - v difference for intact PTH of 29 ± 2% was significantly greater than the filtration fraction indicating renal uptake of intact PTH at sites independent of glomerular filtration. Together, the hepatic and renal clearances of intact PTH accounted for all but a small fraction of the MCR of intact PTH. The MCR of intact PTH, rendered biologically inactive by oxidation, was markedly decreased to 8.8 ± 1 ml/min per kg. The a - v difference of oxidized intact PTH was reduced both in the liver and kidney. These data suggested that the high uptake rates of intact PTH are dependent, at least in part, upon sites recognizing only biologically active PTH.

Chronic renal failure (CRF) decreased the MCR of intact PTH to 11.3 ± 1.3 ml/min per kg (n = 10). Both the hepatic and renal a - v differences of intact PTH were reduced in dogs with CRF. This resulted in reductions in the hepatic and renal clearances of intact PTH. These studies identify the liver as a major extrarenal site of PTH metabolism affected by CRF. They suggest that CRF impairs the function of the major uptake sites involved in intact PTH metabolism.

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Selected References

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

  1. Arnaud C. D., Goldsmith R. S., Bordier P. J., Sizemore G. W. Influence of immunoheterogeneity of circulating parathyroid hormone on results of radioimmunoassays of serum in man. Am J Med. 1974 Jun;56(6):785–793. doi: 10.1016/0002-9343(74)90806-7. [DOI] [PubMed] [Google Scholar]
  2. Barrett P. Q., Neuman W. F. The cleavage and adsorption of parathyroid hormone at high dilution: implications for receptor binding studies. Biochim Biophys Acta. 1978 Jun 15;541(2):223–233. doi: 10.1016/0304-4165(78)90395-1. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Carone F. A., Peterson D. R. Hydrolysis and transport of small peptides by the proximal tubule. Am J Physiol. 1980 Mar;238(3):F151–F158. doi: 10.1152/ajprenal.1980.238.3.F151. [DOI] [PubMed] [Google Scholar]
  5. Cohn D. V., Griffith F. D., Levy R. Parathyroid extract-induced changes in the oxidation of citrate, succinate and other organic acids by liver. Endocrinology. 1965 Oct;77(4):683–691. doi: 10.1210/endo-77-4-683. [DOI] [PubMed] [Google Scholar]
  6. D'Amour P., Segre G. V., Roth S. I., Potts J. T., Jr Analysis of parathyroid hormone and its fragments in rat tissues: chemical identification and microscopical localization. J Clin Invest. 1979 Jan;63(1):89–98. doi: 10.1172/JCI109283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Freitag J. J., Martin K. J., Conrades M. B., Slatopolsky E. Metabolism of parathyroid hormone by fetal rat calvaria. Endocrinology. 1979 Feb;104(2):510–516. doi: 10.1210/endo-104-2-510. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. 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]
  11. Hamilton J. W., Spierto F. W., MacGregor R. R., Cohn D. V. Studies on the biosynthesis in vitro of parathyroid hormone. II. The effect of calcium and magnesium on synthesis of parathyroid hormone isolated from bovine parathyroid tissue and incubation medium. J Biol Chem. 1971 May 25;246(10):3224–3233. [PubMed] [Google Scholar]
  12. Hruska K. A., Blondin J., Bass R., Santiago J., Thomas L., Altsheler P., Martin K., Klahr S. Effect of intact parathyroid hormone on hepatic glucose release in the dog. J Clin Invest. 1979 Oct;64(4):1016–1023. doi: 10.1172/JCI109538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hruska K. A., Kopelman R., Rutherford W. E., Klahr S., Slatopolsky E., Greenwalt A., Bascom T., Markham J. Metabolism in immunoreactive parathyroid hormone in the dog. The role of the kidney and the effects of chronic renal disease. J Clin Invest. 1975 Jul;56(1):39–48. doi: 10.1172/JCI108077. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hunziker W. H., Blum J. W., Fischer J. A. Plasma kinetics of exogenous bovine parathyroid hormone in calves. Pflugers Arch. 1977 Nov 23;371(3):185–192. doi: 10.1007/BF00586257. [DOI] [PubMed] [Google Scholar]
  15. KETTERER S. G., WIEGAND B. D., RAPAPORT E. Hepatic uptake and biliary excretion of indocyanine green and its use in estimation of hepatic blood flow in dogs. Am J Physiol. 1960 Sep;199:481–484. doi: 10.1152/ajplegacy.1960.199.3.481. [DOI] [PubMed] [Google Scholar]
  16. Katz A. I., Rubenstein A. H. Metabolism of proinsulin, insulin, and C-peptide in the rat. J Clin Invest. 1973 May;52(5):1113–1121. doi: 10.1172/JCI107277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kau S. T., Maack T. Transport and catabolism of parathyroid hormone in isolated rat kidney. Am J Physiol. 1977 Nov;233(5):F445–F454. doi: 10.1152/ajprenal.1977.233.5.F445. [DOI] [PubMed] [Google Scholar]
  18. Maack T., Johnson V., Kau S. T., Figueiredo J., Sigulem D. Renal filtration, transport, and metabolism of low-molecular-weight proteins: a review. Kidney Int. 1979 Sep;16(3):251–270. doi: 10.1038/ki.1979.128. [DOI] [PubMed] [Google Scholar]
  19. Martin K. J., Freitag J. J., Conrades M. B., Hruska K. A., Klahr S., Slatopolsky E. Selective uptake of the synthetic amino terminal fragment of bovine parathyroid hormone by isolated perfused bone. J Clin Invest. 1978 Aug;62(2):256–261. doi: 10.1172/JCI109124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Martin K. J., Hruska K. A., Lewis J., Anderson C., Slatopolsky E. The renal handling of parathyroid hormone. Role of peritubular uptake and glomerular filtration. J Clin Invest. 1977 Oct;60(4):808–814. doi: 10.1172/JCI108834. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Martin K., Hruska K., Greenwalt A., Klahr S., Slatopolsky E. Selective uptake of intact parathyroid hormone by the liver: differences between hepatic and renal uptake. J Clin Invest. 1976 Oct;58(4):781–788. doi: 10.1172/JCI108529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Moxley M. A., Bell N. H., Wagle S. R., Allen D. O., Ashmore J. Parathyroid hormone stimulation of glucose and urea production in isolated liver cells. Am J Physiol. 1974 Nov;227(5):1058–1061. doi: 10.1152/ajplegacy.1974.227.5.1058. [DOI] [PubMed] [Google Scholar]
  23. Neuman W. F., Neuman M. W., Lane K., Miller L., Sammon P. J. The metabolism of labeled parathyroid hormone. V. Collected biological studies. Calcif Tissue Res. 1975 Sep 17;18(4):271–287. doi: 10.1007/BF02546246. [DOI] [PubMed] [Google Scholar]
  24. Neuman W. F., Neuman M. W., Sammon P. J., Simon W., Lane K. The metabolism of labeled parathyroid hormone. III. Studies in rats. Calcif Tissue Res. 1975 Sep 17;18(4):251–261. doi: 10.1007/BF02546244. [DOI] [PubMed] [Google Scholar]
  25. Potts J. T., Jr, Aurbach G. D., Sherwood L. M., Sandoval A. Structural basis of biological and immunological activity of parathyroid hormone. Proc Natl Acad Sci U S A. 1965 Dec;54(6):1743–1751. doi: 10.1073/pnas.54.6.1743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. REISFELD R. A., LEWIS U. J., WILLIAMS D. E. Disk electrophoresis of basic proteins and peptides on polyacrylamide gels. Nature. 1962 Jul 21;195:281–283. doi: 10.1038/195281a0. [DOI] [PubMed] [Google Scholar]
  27. SELDINGER S. I. Catheter replacement of the needle in percutaneous arteriography; a new technique. Acta radiol. 1953 May;39(5):368–376. doi: 10.3109/00016925309136722. [DOI] [PubMed] [Google Scholar]
  28. SHOEMAKER W. C., WALKER W. F., VAN ITALLIE T. B., MOORE F. D. A method for simultaneous catheterization of major hepatic vessels in a chronic canine preparation. Am J Physiol. 1959 Feb;196(2):311–314. doi: 10.1152/ajplegacy.1959.196.2.311. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Segre G. V., Niall H. D., Sauer R. T., Potts J. T., Jr Edman degradation of radioiodinated parathyroid hormone: application to sequence analysis and hormone metabolism in vivo. Biochemistry. 1977 May 31;16(11):2417–2427. doi: 10.1021/bi00630a017. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. Singer F. R., Segre G. V., Habener J. F., Potts J. T., Jr Peripheral metabolism of bovine parathyroid hormone in the dog. Metabolism. 1975 Feb;24(2):139–144. doi: 10.1016/0026-0495(75)90014-1. [DOI] [PubMed] [Google Scholar]
  33. Sutcliffe H. S., Martin T. J., Eisman J. A., Pilczyk R. Binding of parathyroid hormone to bovine kidney-cortex plasma membranes. Biochem J. 1973 Aug;134(4):913–921. doi: 10.1042/bj1340913. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. 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]

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