Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1981 Feb;67(2):439–448. doi: 10.1172/JCI110052

Effects of Hepatectomy, Nephrectomy, and Nephrectomy/Uremia on the Metabolism of Parathyroid Hormone in the Rat

Gino V Segre 1,2, Pierre D'Amour 1,2, Anne Hultman 1,2, John T Potts Jr 1,2
PMCID: PMC370585  PMID: 7462426

Abstract

Reports from several laboratories, showing extensive hepatic extraction of circulating parathyroid hormone, led us to examine the effect of near-total hepatectomy on the metabolism of the hormone to circulating fragments, and on its clearance from plasma. The rate of disappearance of 125I-labeled and unlabeled bovine parathyroid hormone from plasma, and the appearance, disappearance, and chemical and immunochemical characteristics of circulating fragments were examined by gel filtration and either sequence-specific radioimmunoassays or sequence analysis using the Edman reaction. Results from awake rats subjected to near-total hepatectomy were compared with those found in sham-treated, nephrectomized, and short-term uremic rats (studied 2 d after nephrectomy). When compared with the sham-treated group, all other groups clear 125I-labeled hormone more slowly; after hepatectomy, however, the clearance rate is most strikingly decreased.

After injection of intact hormone, the concentration of carboxy-terminal fragments in the circulation of hepatectomized rats is greatly reduced at all time intervals when compared with that in sham-treated rats. Sequence analysis of plasma samples, collected from rats into which 125I-labeled hormone had been injected, shows that carboxy-terminal fragments having positions 34 and 37 of the intact hormone sequence as their amino-terminal amino acids are abundant in sham-treated, nephrectomized, and nephrectomized/uremic rats, but are undetectable in hepatectomized rats. The data suggest that inasmuch as the liver in vivo generates most of the carboxy-terminal fragments resulting from the metabolism of injected hormone, specific cell types within the liver must be the principal locus of the responsible enzyme(s); thus, studies of the enzymic properties of isolated hepatic cells in vitro most likely will yield information of physiologic relevance to the metabolism of the hormone in the intact animal.

Full text

PDF

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. 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]
  3. Canterbury J. M., Bricker L. A., Levey G. S., Kozlovskis P. L., Ruiz E., Zull J. E., Reiss E. Metabolism of bovine parathyroid hormone. Immunological and biological characteristics of fragments generated by liver perfusion. J Clin Invest. 1975 Jun;55(6):1245–1253. doi: 10.1172/JCI108043. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. 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]
  6. DAVIS R., TALMAGE R. V. Evidence for liver inactivation of parathyroid hormone. Endocrinology. 1960 Feb;66:312–314. doi: 10.1210/endo-66-2-312. [DOI] [PubMed] [Google Scholar]
  7. Edman P., Begg G. A protein sequenator. Eur J Biochem. 1967 Mar;1(1):80–91. doi: 10.1007/978-3-662-25813-2_14. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Fischer J. A., Binswanger U., Dietrich F. M. Human parathyroid hormone. Immunological characterization of antibodies against a glandular extract and the synthetic amino-terminal fragments 1-12 and 1-34 and their use in the determination of immunoreactive hormone in human sera. J Clin Invest. 1974 Dec;54(6):1382–1394. doi: 10.1172/JCI107885. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Flueck J. A., Di Bella F. P., Edis A. J., Kehrwald J. M., Arnaud C. D. Immunoheterogeneity of parathyroid hormone in venous effluent serum from hyperfunctioning parathyroid glands. J Clin Invest. 1977 Dec;60(6):1367–1375. doi: 10.1172/JCI108897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Freitag J., Martin K. J., Hruska K. A., Anderson C., Conrades M., Ladenson J., Klahr S., Slatopolsky E. Impaired parathyroid hormone metabolism in patients with chronic renal failure. N Engl J Med. 1978 Jan 5;298(1):29–32. doi: 10.1056/NEJM197801052980107. [DOI] [PubMed] [Google Scholar]
  12. Funovics J. M., Cummings M. G., Shuman L., James J. H., Fischer J. E. An improved nonsuture method for portacaval anastomosis in the rat. Surgery. 1975 May;77(5):661–664. [PubMed] [Google Scholar]
  13. Goldsmith R. S., Furszyfer J., Johnson W. J., Fournier A. E., Sizemore G. W., Arnaud C. D. Etiology of hyperparathyroidism and bone disease during chronic hemodialysis. 3. Evaluation of parathyroid suppressibility. J Clin Invest. 1973 Jan;52(1):173–180. doi: 10.1172/JCI107161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. HUNTER W. M., GREENWOOD F. C. Preparation of iodine-131 labelled human growth hormone of high specific activity. Nature. 1962 May 5;194:495–496. doi: 10.1038/194495a0. [DOI] [PubMed] [Google Scholar]
  15. Habener J. F., Mayer G. P., Dee P. C., Potts J. T., Jr Metabolism of amino- and carboxyl-sequence immunoreactive parathyroid hormone in the bovine: evidence for peripheral cleavage of hormone. Metabolism. 1976 Apr;25(4):385–395. doi: 10.1016/0026-0495(76)90070-6. [DOI] [PubMed] [Google Scholar]
  16. Habener J. F., Powell D., Murray T. M., Mayer G. P., Potts J. T., Jr Parathyroid hormone: secretion and metabolism in vivo. Proc Natl Acad Sci U S A. 1971 Dec;68(12):2986–2991. doi: 10.1073/pnas.68.12.2986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hanley D. A., Takatsuki K., Sultan J. M., Schneider A. B., Sherwood L. M. Direct release of parathyroid hormone fragments from functioning bovine parathyroid glands in vitro. J Clin Invest. 1978 Dec;62(6):1247–1254. doi: 10.1172/JCI109245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Keutmann H. T., Aurbach G. D., Dawson B. F., Niall H. D., Deftos L. J., Potts J. T., Jr Isolation and characterization of the bovine parathyroid isohormones. Biochemistry. 1971 Jul 6;10(14):2779–2787. doi: 10.1021/bi00790a020. [DOI] [PubMed] [Google Scholar]
  20. Marcus R., Aurbach G. D. Bioassay of parathyroid hormone in vitro with a stable preparation of adenyl cyclase from rat kidney. Endocrinology. 1969 Nov;85(5):801–810. doi: 10.1210/endo-85-5-801. [DOI] [PubMed] [Google Scholar]
  21. Martin K. J., Hruska K. A., Freitag J. J., Klahr S., Slatopolsky E. The peripheral metabolism of parathyroid hormone. N Engl J Med. 1979 Nov 15;301(20):1092–1098. doi: 10.1056/NEJM197911153012005. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. 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]
  24. 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]
  25. Mayer G. P., Keaton J. A., Hurst J. G., Habener J. F. Effects of plasma calcium concentration on the relative proportion of hormone and carboxyl fragments in parathyroid venous blood. Endocrinology. 1979 Jun;104(6):1778–1784. doi: 10.1210/endo-104-6-1778. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. 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]
  28. Parsons J. A., Reit B., Robinson C. J. A chick bioassay for parathyroid hormone. Endocrinology. 1973 Feb;92(2):454–462. doi: 10.1210/endo-92-2-454. [DOI] [PubMed] [Google Scholar]
  29. Rosenblatt M., Segre G. V., Potts J. T., Jr Synthesis of a fragment of parathyroid hormone, bPTH-(28-48): an inhibitor of hormone cleavage in vivo. Biochemistry. 1977 Jun 28;16(13):2811–2816. doi: 10.1021/bi00632a001. [DOI] [PubMed] [Google Scholar]
  30. Sauer R. T., Niall H. D., Hogan M. L., Keutmann H. T., O'Riordan J. L., Potts J. T., Jr The amino acid sequence of porcine parathyroid hormone. Biochemistry. 1974 Apr 23;13(9):1994–1999. doi: 10.1021/bi00706a033. [DOI] [PubMed] [Google Scholar]
  31. Segre B. V., D'Amour P., Potts J. T. Metabolism of radioiodinated bovine parathyroid hormone in the rat. Endocrinology. 1976 Dec;99(6):1645–1652. doi: 10.1210/endo-99-6-1645. [DOI] [PubMed] [Google Scholar]
  32. Segre G. V., Habener J. F., Powell D., Tregear G. W., Potts J. T. Parathyroid Hormone in Human Plasma: IMMUNOCHEMICAL CHARACTERIZATION AND BIOLOGICAL IMPLICATIONS. J Clin Invest. 1972 Dec;51(12):3163–3172. doi: 10.1172/JCI107143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. 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]
  34. 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]
  35. Segre G. V., Tregear G. W., Potts J. T., Jr Development and application of sequence-specific radioimmunoassays for analysis of the metabolism of parathyroid hormone. Methods Enzymol. 1975;37:38–66. doi: 10.1016/s0076-6879(75)37005-5. [DOI] [PubMed] [Google Scholar]
  36. 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]
  37. 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]

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

RESOURCES