Oral testosterone in male rats and the development of experimental autoimmune encephalomyelitis.
OBJECTIVE
Considering that sex steroids can influence the immune system, we studied the development of experimental autoimmune encephalomyelitis (EAE), a T-cell-mediated autoimmune disease of the central nervous system, and the concomitant cell-mediated immunity in gonadally intact and gonadectomized male Wistar rats given testosterone supplementation.


RESULTS
Sham-operated rats and surgically castrated animals were orally self-administered with vehicle or testosterone added in the water bottle for 20 days before EAE induction. The androgenic effect of oral testosterone self-administration was evidenced by changes in body weight, and in the weights of androgen-dependent testes and seminal vesicles. Testosterone administration reduced the incidence of clinical signs of EAE in sham-operated animals and reversed the clinical symptoms of the disease associated with castrated EAE animals. The clinical signs observed in the different groups correlated with changes in delayed-type hypersensitivity and mononuclear cell-proliferative responses to the encephalitogenic myelin basic protein. Moreover, testosterone but not cholesterol supplementation in vitro suppressed the proliferative response of mononuclear cells to myelin basic protein suggesting that testosterone may affect specific immune functions through direct actions on immune cells. Finally, self-administration of testosterone induced also elevated corticosterone levels that in sham-operated rats correlated with the low incidence of the disease and in gonadectomized animals could be involved in the remission of clinical symptoms of EAE.


CONCLUSIONS
These results suggest that orally self-administered testosterone can modulate specific cellular immune responses and serum corticosterone levels leading to changes in the development of EAE.
Macció
Daniela R
DR
Departamento de Química Biológica y Centro de Investigaciones en Química Biológica de Córdoba, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
Calfa
Gastón
G
Roth
German A
GA
D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002784:Cholesterol / Q000276:immunology / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000503:physiopathology; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology*; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D004676:Myelin Basic Protein / Q000276:immunology / Q000494:pharmacology; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D012646:Self Administration; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013737:Testis / Q000187:drug effects / Q000276:immunology; D013739:Testosterone / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D004676:Myelin Basic Protein; D013739:Testosterone; D002784:Cholesterol; D003345:Corticosterone