Abstract
Prepubertal castration of female NZB/NZW (B/W) hybrid mice did not influence mortality, whereas prepubertal castration of male B/W mice caused premature death and enhanced autoantibody formation. Prepubertal castration combined with the administration of sustained estradiolโ17โฮฒ (Eโ2) enhanced mortality and autoantibody development and promoted immune complex nephritis in both sexes. The enhanced mortality observed in castrated males was significantly reduced if they were treated with sustained progesterone (P). Mice of both sexes receiving P had the highest levels of autoantibodies. By contrast, sustained 5โฮฑโdihydrotestosterone (DHT) and testosterone (T) suppressed these autoimmune parameters. The suppressive effect of androgens was not a nonspecific anabolic property, since danazol (a compound with attenuated masculinizing but intact anabolic properties) was ineffective in suppressing disease. AntiDNA antibody formation developed prematurely in males given cyproterone acetate, an antiandrogen. However, this metabolic blocker did not influence mortality or proteinuria. Unexpected early enhancement of mortality was observed in female and male mice castrated and given both Eโ2 and DHT (when compared to shamโoperated controls or mice given Eโ2 alone). When castration was combined with the administration of both Eโ2 and P, mortality was enhanced in males but was similar to Eโ2 alone in females. Androgen therapy was also suppressive when it was delayed and given to female mice with more advanced disease. DHT given to intact 3โmonthโold or castrated 6โmonthโold B/W females significantly improved survival without affecting the serum levels of antiโDNA antibodies. These observations demonstrate that sex hormones significantly modify disease in B/W mice and may have therapeutic potential.