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Biological activities of prostaglandin analogues and metabolites on bone in organ culture

Naturevolume 266pages645647 (1977) | Download Citation

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Abstract

PROSTAGLANDINS, especially the E-series, are potent stimulators of bone resorption in several in vitro systems1–4. Studies with two experimental tumours (HSDM1 mouse fibrosarcoma and VX2 rabbit carcinoma) have indicated that excessive synthesis and secretion of prostaglandin E2 (PGE2) by the neoplastic cells is associated with and seems likely to be responsible for the hypercalcaemia observed in these tumour-bearing animals2,5–8. A similar hypercalcaemic syndrome occurs in some patients with cancer, is associated with excessive PGE2 metabolite excretion in urine and is reversed at least in part by treatment with aspirin-like drugs9,10. Finally, intravenous infusion of PGE2 in intact, unanaesthetised rats causes an increase of plasma calcium concentration11. The most straightforward interpretation of these findings is that PGE2 is secreted by certain tumour cells into plasma in such quantity that the steady-state plasma concentration of PGE2 is sufficiently high to stimulate osseous target cells to resorb bone. An alernative interpretation is that unmeasured intermediates in arachidonic acid metabolism or PGE2 metabolites have sufficient bone resonption-stimulating activity to be the agent acting on bone cells. This hypothesis gains a degree of support from knowledge that some prostaglandin metabolites have longer half lives in plasma than PGE2 itself12. We have now measured the biological activities of several endoperoxide analogues and PGE2 metabolites in a bone culture assay system and compared their potencies with that of PGE2.

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References

  1. 1

    Klein, D. C. & Raisz, L. G. Endocrinology 86, 1436–1440 (1970).

  2. 2

    Tashjian, A. H., Jr, Voelkel, E. F., Levine, L. & Goldhaber, P. J. exp. Med., 136, 1329–1343 (1972).

  3. 3

    Dietrich, J. W., Goodson, J. M. & Raisz, L. G. Prostaglandins 10, 231–240 (1975).

  4. 4

    Powles, T. J., Easty, D. M., Easty, G. C., Bondy, P. K. & Munro-Neville, A. Nature new Biol. 245, 83–84 (1973).

  5. 5

    Tashjian, A. H., Jr, Voelkel, E. F., Goldhaber, P. & Levine, L. Fedn Proc. 33, 81–86 (1974).

  6. 6

    Tashjian, A. H., Jr., Voelkel, E. F., Goldhaber, P. & Levine, L. Prostaglandins 3, 515–524 (1973).

  7. 7

    Voelkel, E. F., Tashjian, A. H., Jr. Franklin, R., Wasserman, E. & Levine, L. Metabolism 24, 973–986 (1975).

  8. 8

    Tashjian, A. H., Jr, Voelkel, E. F. & Levine, L. Biochem. biophys. Res. Commun. 74, 199–207 (1977).

  9. 9

    Seyberth, H. W. et al. New Engl. J. Med. 293, 1278–1283 (1975).

  10. 10

    Tashjian, A. H., Jr, New Engl. J. Med. 293, 1317–1318 (1975).

  11. 11

    Franklin, R. B. & Tashjian, A. H., Jr, Endocrinology 97, 240–243 (1975).

  12. 12

    Samuelsson, B., Granström, E., Green, K., Hamburg, M. & Hammarström, S. A. Rev. Biochem. 44, 669–695 (1975).

  13. 13

    Corey, E. J., Nicolaou, K. C., Machida, Y., Malmsten, C. L. & Samuelsson, B. Proc. natn. Acad. Sci. U.S.A. 72, 3355–3358 (1975).

  14. 14

    Robinson, D. R., Tashjian, A. H., Jr. & Levine, L. J. clin. Invest. 56, 1181–1188 (1975).

  15. 15

    Seyberth, H. W., Hubbard, W. C. Jr, Morgan, J. L., Sweetman, B. J. & Oates, J. A. Clin. Res. 24, 370A (1976).

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Affiliations

  1. Harvard School of Dental Medicine, Harvard Medical School, Boston, Massachusetts, 02115

    • ARMEN H. TASHJIAN JR
    • , JANET E. TICE
    •  & KAREN SIDES

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https://doi.org/10.1038/266645a0

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