Calcified Tissue International

, Volume 34, Issue 1, pp 197–203 | Cite as

Parathyroid hormone and calcitonin interactions in bone: Irradiation-induced inhibition of escape in vitro

  • Nancy S. Krieger
  • Roy S. Feldman
  • Armen H. TashjianJr.


Calcitonin (CT) inhibits hormonally stimulated bone resorption only transiently in vitro. This phenomenon has been termed “escape,” but the mechanism for the effect is not understood. One possible explanation is that bone cell differentiation and recruitment of specific precursor cells, in response to stimulators of resorption, lead to the appearance of osteoclasts that are unresponsive to CT. To test this hypothesis, cell proliferation in neonatal mouse calvaria in organ culture was inhibited by irradiation from a cobalt-60 source. At a dose of 6000 R, [3H]thymidine incorporation into intact calvaria was inhibited approximately 90%. Irradiation had no effect on the resorptive response to 0.1 U/ml parathyroid hormone (PTH). However, irradiation induced a dose-dependent inhibition of the escape response which was maximal at 6000 R. A dose of 6000 R did not affect the binding of125I-salmon CT to calvaria and decreased PTH stimulation of cyclic AMP release from bone without affecting the cyclic AMP response to CT. Although irradiation caused a dose-dependent inhibition of DNA synthesis, the dose-response curves for that effect and inhibition of escape were not superimposable.

A morphologic study of hormonally treated calvaria demonstrated that irradiation prevented the early increase in number of osteoclasts in PTH-treated calvaria that had been observed previously in unirradiated bones. Autoradiography showed that irradiation also prevented the PTH-stimulated recruitment of newly divided mononuclear cell precursors into osteoclasts. This may be correlated with the effect of irradiation to prevent the loss of responsiveness to CT in the presence of PTH.

Key words

Parathyroid hormone Calcitonin Bone Escape Irradiation 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Raisz, L. G.: Mechanisms of bone resorption. In G. D. Aurbach (ed.): Handbook of Physiology, Section 7, Vol. VII, pp. 117–136. American Physiological Society, Washington, D.C., 1976Google Scholar
  2. 2.
    Tashjian, A. H., Jr., Wright, D. R., Ivey, J. L., Pont, A.: Calcitonin binding sites in bone: relationships to biological response and “escape,” Recent Prog. Horm. Res.34:285–331, 1978PubMedGoogle Scholar
  3. 3.
    Wener, J. A., Gorton, S. J., Raisz, L. G.: Escape from inhibition of resorption in cultures of fetal bone treated with calcitonin and parathyroid hormone, Endocrinology90:752–759, 1972PubMedCrossRefGoogle Scholar
  4. 4.
    Catt, K. J., Harwood, J. P., Aguilera, G., Dufau, M. L.: Hormonal regulation of peptide receptors and target cell responses, Nature280:109–116, 1979CrossRefPubMedGoogle Scholar
  5. 5.
    Robinson, D. R., Tashjian, A. H., Jr., Levine, L.: Prostaglandin-stimulated bone resorption by rheumatoid synovia, J. Clin. Invest.56:1181–1188, 1975PubMedGoogle Scholar
  6. 6.
    Tashjian, A. H., Jr., Levine, L.: Epidermal growth factor stimulates prostaglandin production and bone resorption in cultured mouse calvaria, Biochem. Biophys. Res. Commun.85:966–975, 1978PubMedCrossRefGoogle Scholar
  7. 7.
    Brown, B. L., Albano, J. D. M., Ekins, R. P., Sgherzi, A. M., Tampion, W.: A simple and sensitive saturation assay method for the measurement of adenosine 3′:5′-cyclic monophosphate, Biochem. J.121:561–562, 1971PubMedGoogle Scholar
  8. 8.
    Tashjian, A. H., Jr.: Immunoassay of thyrocalcitonin. I. The method and its serological specificity, Endocrinology84:140–148, 1969PubMedGoogle Scholar
  9. 9.
    Greenwood, F. C., Hunter, W. H., Glover, J. S.: The preparation of131I-labeled human growth hormone of high specific radioactivity, Biochem. J.89:114–123, 1963PubMedGoogle Scholar
  10. 10.
    Thomas, P. S., Farquhar, M. N.: Specific measurement of DNA in nuclei and nucleic acids using diaminobenzoic acid, Anal. Biochem.89:35–44, 1978CrossRefPubMedGoogle Scholar
  11. 11.
    Feldman, R. S., Krieger, N. S., Tashjian, A. H., Jr.: Effects of parathyroid hormone and calcitonin on osteoclast formationin vitro, Endocrinology107:1137–1143, 1980PubMedGoogle Scholar
  12. 12.
    Snedecor, G. W., Cochran, W. G.: Statistical Methods. Iowa State University Press, Ames, Iowa, 1967Google Scholar
  13. 13.
    Aurbach, G. D., Chase, L. R.: Cyclic nucleotides and biochemical actions of parathyroid hormone and calcitonin. In G. D. Aurbach (ed.): Handbook of Physiology, Section 7, Vol. VII, pp. 353–381. American Physiological Society, Washington, D.C., 1976Google Scholar
  14. 14.
    Ivey, J. L., Wright, D. R., Tashjian, A. H., Jr.: Bone resorption in organ culture. Inhibition by the divalent cation ionophore A23187 and X-537A, J. Clin. Invest.58:1327–1338, 1976PubMedCrossRefGoogle Scholar
  15. 15.
    Krieger, N. S., Feldman, R. S., Tashjian, A. H., Jr.: Multihormonal effects on osteoclast formationin vitro, Calcif. Tissue Int.28:149, 1979 (abst.)Google Scholar
  16. 16.
    Tatevossian, A.: Effect of parathyroid extract on blood calcium and osteoclast count in mice, Calcif. Tissue Res.11:251–257, 1973PubMedGoogle Scholar
  17. 17.
    King, G. J., Holtrop, M. E., Raisz, L. G.: The relationship of ultrastructural changes in osteoclasts to resorption in bone cultures stimulated with parathyroid hormone, Metab. Bone Dis. Rel. Res.1:67–74, 1978CrossRefGoogle Scholar
  18. 18.
    Goldhaber, P., Little, J. B.: The effect of various doses of x-irradiation on bone resorption and bone formation in tissue culture, J. Cell Biol.27:35, 1965 (abst.)CrossRefGoogle Scholar
  19. 19.
    Nijweide, P. J., Gaillard, P. J., Hekkelman, J. W., Hermann-Erlee, M. P. M., v.d. Plas, A., Vogt, G. B.: The effects of x-irradiation on embryonic bone and cartilagein vitro, Radiat. Res.73:234–250, 1978PubMedGoogle Scholar
  20. 20.
    Little, J. B., Williams, J. R.: Effects of ionizing radiation on mammalian cells. In: S. R. Geiger, H. L. Falk, S. D. Murphy, D. H. K. Lee (eds.): Handbook of Physiology, Section 9, pp. 127–155. American Physiological Society, Bethesda, MD, 1977Google Scholar
  21. 21.
    Patrick, G.: Effects of radiation on cell membranes. In: G. A. Jamieson, D. M. Robinson (eds.): Mammalian Cell Membranes, Vol. 5, pp. 72–80. Butterworths, London, 1977Google Scholar
  22. 22.
    Holtrop, M. E., Raisz, L. G., Simmons, H. A.: The effect of parathyroid hormone, colchicine and calcitonin on the ultrastructure and the activity of osteoclasts in organ culture, J. Cell. Biol.60:346–355, 1974CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 1982

Authors and Affiliations

  • Nancy S. Krieger
    • 1
  • Roy S. Feldman
    • 2
  • Armen H. TashjianJr.
    • 1
  1. 1.Laboratory of Toxicology, Harvard School of Public Health, Department of PharmacologyHarvard Medical SchoolBostonUSA
  2. 2.Harvard School of Dental Medicine and Veterans Administration Outpatient ClinicBostonUSA

Personalised recommendations