Oestrogen-induced suppression of collagen arthritis; 17 beta-oestradiol is therapeutically active in normal and castrated F1 hybrid mice of both sexes.
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.
Jansson
L
L
Department of Medical and Physiological Chemistry, Uppsala University, Sweden.
Holmdahl
R
R
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000517:prevention & control*; D003094:Collagen; D004958:Estradiol / Q000627:therapeutic use; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006824:Hybridization, Genetic; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains / Q000235:genetics; D009919:Orchiectomy; D010052:Ovariectomy; D013739:Testosterone / Q000494:pharmacology
D004967:Estrogens; D013739:Testosterone; D004958:Estradiol; D003094:Collagen