Abstract
GROWTH and differentiation of mammalian cells is considered to be controlled in part by the interaction of various hormones and other growth promoting factors1. Corticosteroids are hormones with a wide range of tissue specificity, intracellular receptor proteins having been described in various tissues2 and cultured cells3,4. Glucocorticoids exert paradoxical effects on cell proliferation. Thus they promote cell growth of the mammary gland epithelium in mice and rats5,6 and in mouse and rat organ7–9 and rat tissue culture systems10, and DNA synthesis in cultured parenchymal rat liver cells11. But they inhibit all stages of the inflammatory response, including the reparative growth of fibroblasts, loss of immune competence due to damage to lymphocytes, lipolysis and other anabolic (contra-insulin) effects in adipose tissue12. In cultured fibroblasts hydrocortisone can, in different conditions, either stimulate13 or inhibit14–16 DNA synthesis and cell devision. The growth promoting effects of the corticosteroids in fibroblasts and mammary epithelial cells may be related to their ability to synergise with the fibroblast growth factor (FGF) (refs 17 and 18) and prolactin10 respectively. Growth inhibitory effects may be due to the predominantly catabolic action of the glucocorticoids12. Here we report that hydrocortisone can inhibit specifically the stimulation of DNA synthesis and cell division induced by prostaglandin F2α (ref. 19) in Swiss mouse 3T3 and 3T6 cells. We suggest that the cell-growth-regulating properties of the corticosteroids are in part dependent on the identity of the co-inducing growth controlling factors, and that glucocorticoid inhibition of prostaglandin-stimulated cell growth may have a role in the anti-inflammatory response.
Similar content being viewed by others
References
Armelin, H. A., Nishikawa, K. & Sato, G. H. in Control of Proliferation in Animal Cells 1 (eds Clarkson, B. & Baserga, R.) 97–104 (Cold Spring Harbor Laboratory, New York, 1974).
King, R. & Mainwaring, W. I. P. in Steroid-Cell Interactions 102–161 (Butterworths, London, 1974).
Ishii, D. N., Pratt, W. B. & Aronow, L., Biochemistry 11, 3896–3904 (1972).
Baxter, J. D., Harris, A. W., Tomkins, G. M. & Cohn, M., Science 171, 189–191 (1971).
Nandi, S. J. J. natn. Cancer Inst. 21, 1039–1055 (1958).
Lyons, R. W., Li, C. H. & Johnson, R. E. Recent Prog. Hormone Res. 14, 219–254 (1958).
Topper, Y. J. & Oka, T. in Effects of Drugs on Cellular Control Mechanisms. (eds Rabin, B. R. & Freedman, R. B.) 131–150 (Macmillan, London, 1971).
Dilley, J. Endocrinology 50, 501–505 (1971).
Hallowes, R. C., Wang, D. & Lewis, D. J. J. Endocrinology 57, 253–264 (1973).
Rudland, P. S., Hallowes, R., Lewis, D. & Durbin, H. J. Cell Biol. (in the press).
Leffert, H. L. J. Cell Biol. 62, 792–801 (1974).
Gorbman, A. & Bern, H. A. in A Text Book of Comparative Endocrinology 324–325 (Wiley, New York, 1964).
Thrash, C. R. & Cunningham, D. D. Nature 242, 399–401 (1973).
Cox, R. P. & Macleod, C. M. J. gen. Physiol. 45, 439–485 (1962).
Ruhman, A. G. & Berliner, D. L. Endocrinology 76, 916–927 (1965).
Fodge, D. W. & Rubin, H. Nature 257, 804–806 (1975).
Gospodarowicz, D. Nature 249, 123–127 (1974).
Rudland, P. S., Seifert, W. E. & Gospodarowicz, D. Proc. natn. Acad. Sci. U.S.A. 72, 2724–2728 (1974).
Jimenez de Asua, L., Clingan, D. & Rudland, P. S. Proc. natn. Acad. Sci. U.S.A. 72, 2724–2728 (1975).
Thrash, C. R., Ho, T.-S. & Cunningham, D. D. J. biol. Chem. 249, 6099–6103 (1974).
Ferreira, S. H. & Vane, J. R. in The Prostaglandins 2 (ed. Ramwell, P. W.) 1–47 (Plenum, New York, 1974).
Bennett, A. & Pasner, J. Br. J. Pharmac. 42, 584–594 (1971).
Bundy, G. L. Tetrahedron Lett. 24, 1957–1960 (1975).
Gray, J. G., Pratt, W. B. & Aronow, L., Biochemistry 10, 277–283 (1971).
Makman, M. H., Dvorkin, B. & White, A. Proc. natn. Acad. Sci. U.S.A. 68, 1269–1273 (1971).
Lever, J. E., Clingan, D. & Jimenez de Asua, L. Biochem. biophys. Res. Commun. 71, 136–143 (1976).
Braun, T. & Hechter, O. Proc. natn. Acad. Sci. U.S.A. 66, 995–1001 (1970).
Cope, C. L. in Adrenal Steroids and Disease 232–239 (Pitman Medical, London, 1972).
Williamson, M. B. in The Healing of Wounds. 113–147 (McGraw Hill, London, 1957).
Kantrowitz, F., et al., Nature 258, 737–741 (1975).
Todaro, G. J. & Green, H. J. Cell Biol. 17, 299–313 (1963).
Bush, H. thesis, London Univ. (1975).
Burton, K. Biochem. J. 62, 315 (1956).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
DE ASUA, L., CARR, B., CLINGAN, D. et al. Specific glucocorticoid inhibition of growth promoting effects of prostaglandin F2α on 3T3 cells. Nature 265, 450–452 (1977). https://doi.org/10.1038/265450a0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/265450a0
- Springer Nature Limited