Influence of castration, alone or combined with thymectomy, on the development of diabetes in the nonobese diabetic mouse.

The nonobese diabetic (NOD) mouse is a recognized model for studying immunologically-mediated insulin-dependent diabetes mellitus. The disease appears with a greater preponderance in females than in males. Castration at weaning led to a significant increase in the prevalence of diabetes in NOD males, whereas a tendency to a decreased prevalence was observed in NOD females. Castration combined with thymectomy was found to further increase the prevalence of diabetes in NOD males, whereas in females castration reversed the effect of thymectomy. These results on changes in diabetes prevalence were corroborated by the degree of lymphocytic infiltration directed toward the pancreatic islets of Langerhans. Taken together these results indicate a direct relationship between the endocrine and immune systems, whereby orchidectomy has a deleterious effect on the immunopathogenesis of diabetes. In addition, we examined whether the distribution of lymphocyte subpopulations, mitogen reactivity, lymphokine production, and in vivo response to a thymus-dependent antigen, such as sheer red blood cell, were dependent or independent of the sex steroid environment.