Peripubertal orchidectomy transitorily affects age-associated thymic involution in rats

Abstract

The role of gonadal hormones in induction and, particularly, maintenance/ progression of rat thymic involution, which normally starts around puberty, was reassessed by examining the effects of peripubertal orchidectomy on thymic weight and morphometric parameters at different times up to the age of 10 months. Up to 6 months post-castration both thymic weight and cellularity in orchidectomized ( Cx) rats were greater than in age-matched control rats, sham Cx ( Sx). The increase in thymic cellularity reflected an increase in thymocyte proliferation rate ( the proportion of proliferating cells was 18.6 +/- 0.7% in 2-month-old Cx ( N = 5) vs 13.4 +/- 0.3% ( N = 5) in age-matched Sx rats) followed by reduced sensitivity to apoptotic signals ( apoptotic thymocytes were 9.8 +/- 0.9% in 2-month-old Cx ( N = 5) vs 15.5 +/- 0.3% ( N = 5) age-matched Sx rats). However, 9 months post-orchidectomy, neither thymic weight and cellularity nor any of the morphometric parameters analyzed differed between Cx and control rats. The reduction of thymic cellularity in Cx rats to control values may be related to increased sensitivity of their thymocytes to apoptotic signals in culture ( 72.6 +/- 1.2% in 10-month-old vs 9.8 +/- 0.9% in 2-month-old Cx rats) followed by reduced responsiveness to proliferative stimuli ( 14.1 +/- 0.2% in 10-month-old vs 18.6 +/- 0.7% in 2-month-old Cx rats). Thus, the study indicates that the effects of peripubertal orchidectomy on thymic weight and cellularity, as well as on the main morphometric indices, are long-lasting but not permanent, i.e., that removal of the testes can only postpone but not prevent age-related organ atrophy and consequently functional deterioration of the immune system.