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. 1992 Sep;89(3):446–451. doi: 10.1111/j.1365-2249.1992.tb06978.x

Oestrogen-induced suppression of collagen arthritis; 17 beta-oestradiol is therapeutically active in normal and castrated F1 hybrid mice of both sexes.

L Jansson 1, R Holmdahl 1
PMCID: PMC1554486  PMID: 1516260

Abstract

The F1 hybrid mouse strain, from B10Q and DBA/1 parentals (the QD strain), is highly susceptible to induction of type II collagen-induced arthritis, an experimental model for rheumatoid arthritis. Males are more susceptible than females. Oophorectomy enhances susceptibility to arthritis and treatment with physiological doses of 17 beta-oestradiol (E2) suppresses disease. E2 treatment lowers the incidence of arthritis also in non-castrated and castrated males, showing that the anti-arthritic effect by oestrogen is not dependent on either sex hormone imprinting effects or interference with male sex hormones. Testosterone treatment of normal females, but not of castrated females, exaggerated development of the disease. In the testosterone-treated normal females, the oestrogen effect on vaginal smear was abolished and ovarian weight decreased, suggesting that the testosterone-mediated enhancing effect is caused by inhibition of ovarian oestrogen production. The crucial importance of oestrogens for the development of arthritis is focused on the effectiveness of treatment with gestation-related doses of E2 of normal, non-castrated females.

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Selected References

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  1. Carlsten H., Tarkowski A., Holmdahl R., Nilsson L. A. Oestrogen is a potent disease accelerator in SLE-prone MRL lpr/lpr mice. Clin Exp Immunol. 1990 Jun;80(3):467–473. doi: 10.1111/j.1365-2249.1990.tb03311.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Grossman C. J. Regulation of the immune system by sex steroids. Endocr Rev. 1984 Summer;5(3):435–455. doi: 10.1210/edrv-5-3-435. [DOI] [PubMed] [Google Scholar]
  3. Hannaford P. C., Kay C. R., Hirsch S. Oral contraceptives and rheumatoid arthritis: new data from the Royal College of General Practitioners' oral contraception study. Ann Rheum Dis. 1990 Oct;49(10):744–746. doi: 10.1136/ard.49.10.744. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Hazes J. M., Dijkmans B. C., Vandenbroucke J. P., de Vries R. R., Cats A. Reduction of the risk of rheumatoid arthritis among women who take oral contraceptives. Arthritis Rheum. 1990 Feb;33(2):173–179. doi: 10.1002/art.1780330204. [DOI] [PubMed] [Google Scholar]
  5. Hernandez-Avila M., Liang M. H., Willett W. C., Stampfer M. J., Colditz G. A., Rosner B., Chang R. W., Hennekens C. H., Speizer F. E. Exogenous sex hormones and the risk of rheumatoid arthritis. Arthritis Rheum. 1990 Jul;33(7):947–953. doi: 10.1002/art.1780330705. [DOI] [PubMed] [Google Scholar]
  6. Holmdahl R., Jansson L., Andersson M. Female sex hormones suppress development of collagen-induced arthritis in mice. Arthritis Rheum. 1986 Dec;29(12):1501–1509. doi: 10.1002/art.1780291212. [DOI] [PubMed] [Google Scholar]
  7. Holmdahl R., Jansson L., Andersson M., Jonsson R. Genetic, hormonal and behavioural influence on spontaneously developing arthritis in normal mice. Clin Exp Immunol. 1992 Jun;88(3):467–472. doi: 10.1111/j.1365-2249.1992.tb06473.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Holmdahl R., Karlsson M., Andersson M. E., Rask L., Andersson L. Localization of a critical restriction site on the I-A beta chain that determines susceptibility to collagen-induced arthritis in mice. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9475–9479. doi: 10.1073/pnas.86.23.9475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Jansson L., Holmdahl R. Oestrogen induced suppression of collagen arthritis. IV: Progesterone alone does not affect the course of arthritis but enhances the oestrogen-mediated therapeutic effect. J Reprod Immunol. 1989 May;15(2):141–150. doi: 10.1016/0165-0378(89)90033-8. [DOI] [PubMed] [Google Scholar]
  10. Jansson L., Mattsson A., Mattsson R., Holmdahl R. Estrogen induced suppression of collagen arthritis. V: Physiological level of estrogen in DBA/1 mice is therapeutic on established arthritis, suppresses anti-type II collagen T-cell dependent immunity and stimulates polyclonal B-cell activity. J Autoimmun. 1990 Jun;3(3):257–270. doi: 10.1016/0896-8411(90)90145-i. [DOI] [PubMed] [Google Scholar]
  11. Lahita R. G. Sex steroids and the rheumatic diseases. Arthritis Rheum. 1985 Feb;28(2):121–126. doi: 10.1002/art.1780280202. [DOI] [PubMed] [Google Scholar]
  12. Larsson P., Goldschmidt T. J., Klareskog L., Holmdahl R. Oestrogen-mediated suppression of collagen-induced arthritis in rats. Studies on the role of the thymus and of peripheral CD8+ T lymphocytes. Scand J Immunol. 1989 Dec;30(6):741–747. doi: 10.1111/j.1365-3083.1989.tb02484.x. [DOI] [PubMed] [Google Scholar]
  13. Luster M. I., Hayes H. T., Korach K., Tucker A. N., Dean J. H., Greenlee W. F., Boorman G. A. Estrogen immunosuppression is regulated through estrogenic responses in the thymus. J Immunol. 1984 Jul;133(1):110–116. [PubMed] [Google Scholar]
  14. Mattsson R., Mattsson A., Holmdahl R., Whyte A., Rook G. A. Maintained pregnancy levels of oestrogen afford complete protection from post-partum exacerbation of collagen-induced arthritis. Clin Exp Immunol. 1991 Jul;85(1):41–47. doi: 10.1111/j.1365-2249.1991.tb05679.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Novotny E. A., Raveche E. S., Sharrow S., Ottinger M., Steinberg A. D. Analysis of thymocyte subpopulations following treatment with sex hormones. Clin Immunol Immunopathol. 1983 Aug;28(2):205–217. doi: 10.1016/0090-1229(83)90155-1. [DOI] [PubMed] [Google Scholar]
  16. Roubinian J. R., Talal N., Greenspan J. S., Goodman J. R., Siiteri P. K. Effect of castration and sex hormone treatment on survival, anti-nucleic acid antibodies, and glomerulonephritis in NZB/NZW F1 mice. J Exp Med. 1978 Jun 1;147(6):1568–1583. doi: 10.1084/jem.147.6.1568. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Steinberg A. D., Melez K. A., Raveche E. S., Reeves J. P., Boegel W. A., Smathers P. A., Taurog J. D., Weinlein L., Duvic M. Approach to the study of the role of sex hormones in autoimmunity. Arthritis Rheum. 1979 Nov;22(11):1170–1176. doi: 10.1002/art.1780221103. [DOI] [PubMed] [Google Scholar]
  18. Stimson W. H. Oestrogen and human T lymphocytes: presence of specific receptors in the T-suppressor/cytotoxic subset. Scand J Immunol. 1988 Sep;28(3):345–350. doi: 10.1111/j.1365-3083.1988.tb01459.x. [DOI] [PubMed] [Google Scholar]
  19. Vandenbroucke J. P., Witteman J. C., Valkenburg H. A., Boersma J. W., Cats A., Festen J. J., Hartman A. P., Huber-Bruning O., Rasker J. J., Weber J. Noncontraceptive hormones and rheumatoid arthritis in perimenopausal and postmenopausal women. JAMA. 1986 Mar 14;255(10):1299–1303. [PubMed] [Google Scholar]
  20. Waites G. T., Whyte A. Effect of pregnancy on collagen-induced arthritis in mice. Clin Exp Immunol. 1987 Mar;67(3):467–476. [PMC free article] [PubMed] [Google Scholar]

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