Tamoxifen exerts testosterone-dependent and independent effects on thymic involution.
Circulating testosterone concentrations and seminal vesicles weights, as well as thymus and spleen weights and histology were assessed in male Wistar rats from the infantile to post-pubertal period. The widely used anti-estrogenic agent tamoxifen was then administered in adult intact and castrated male rats and its long-term effects on thymic involution and splenic growth were examined. The results showed that: (1) age-related involution of the male thymus from the juvenile period through puberty to post-puberty depends on the rising testosterone levels and represents mainly a decrease of thymic lymphoid-cell elements; (2) tamoxifen administration reverses thymic involution in intact adult male rats and this effect is related to a dose-dependent, tamoxifen-induced castration and decrease of testosterone levels; (3) the changes of circulating testosterone levels, either resulting from maturity, or induced by tamoxifen or by castration, have a minimal effect on splenic growth and weight; and (4) in contrast to intact animals, administration of tamoxifen at pharmacological doses to adult castrated rats results in thymic regression. Underscoring the critical role of testosterone on thymic involution, these findings show that tamoxifen is able to reverse ageing changes in the thymus by suppressing testosterone production, while conversely, exerts thymolytic effects in the absence of androgens.
Sfikakis
P P
PP
First Department of Propaedeutic Medicine, Athens University Medical School, Greece. psfikaki@compulink.gr
Kostomitsopoulos
N
N
Kittas
C
C
Stathopoulos
J
J
Karayannacos
P
P
Dellia-Sfikakis
A
A
Mitropoulos
D
D
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004965:Estrogen Antagonists / Q000494:pharmacology*; D008297:Male; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012669:Seminal Vesicles / Q000033:anatomy & histology / Q000187:drug effects / Q000254:growth & development; D013154:Spleen / Q000033:anatomy & histology / Q000187:drug effects* / Q000254:growth & development; D013629:Tamoxifen / Q000494:pharmacology*; D013739:Testosterone / Q000097:blood*; D013950:Thymus Gland / Q000033:anatomy & histology / Q000187:drug effects* / Q000254:growth & development
D004965:Estrogen Antagonists; D013629:Tamoxifen; D013739:Testosterone