Effects of ovariectomy and androgen treatment on the thymic pathology of NZB X SJL mice.

Aging (NZB X SJL)F1 (NS) mice provide a unique model of thymic pathology occurring in females but not in males and characterized by the intrathymic accumulation of mature T cells and B cells. Here, we studied the basis for the sex-related difference in the development of this thymic pathology. In the reverse (SJL X NZB)F1 hybrids, a similar pathology was also observed only in females which suggests that its sex-dependency does not involve sex-linked gene(s) but rather hormonal influences. Ovariectomy of NS females reduced but did not prevent the accumulation of T and B cells in the thymus indicating that estrogens play a minimal role in this thymic pathology. In contrast, chronic dihydrotestosterone (DHT)-treatment of females, started at 4 weeks of age, inhibited the development of thymic lesions. Consistently, orchidectomy of NS males induced the appearance of 'female-like' thymic lesions that could be prevented by DHT-treatment. This demonstrates that the absence of thymic disease in NS males primarily reflects an inhibitory action of androgens. Evidence was obtained that androgens also decrease the production of anti-ds DNA antibodies in NS mice.