Peripubertal orchidectomy transitorily affects age-associated thymic involution in rats

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 percent in 2-month-old Cx (N = 5) vs 13.4 ± 0.3 percent (N = 5) in age-matched Sx rats) followed by reduced sensitivity to apoptotic signals (apoptotic thymocytes were 9.8 ± 0.9 percent in 2-month-old Cx (N = 5) vs 15.5 ± 0.3 percent (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 percent in 10-month-old vs 9.8 ± 0.9 percent in 2-month-old Cx rats) followed by reduced responsiveness to proliferative stimuli (14.1 ± 0.2 percent in 10-month-old vs 18.6 ± 0.7 percent 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.

Stereological analysis of the sexually mature rat thymus after orchidectomy.

To assess the significance of gonadal function in the maintenance of thymic structure, male, sexually mature, 60 days old rats were bilaterally orchidectomized and the volumes of both the thymic compartments, total cellularity of each of them, as well as density (Nv) and mean diameter (D) of thymocytes within the specific thymic regions were stereologically analyzed 3, 7 and 15 days later. Three days after the orchidectomy a decrease in the thymic weight, and a reduction of both the cortical and medullary volumes, were observed. The reduction in cortical volume was followed by a decrease in overall number of the cortical thymocytes, suggesting an enhanced process of thymocyte death. In the same animals, the total number of the medullary thymocytes as well as D remained unchanged. Seven days after orchidectomy both volume of the cortex and total number of the cortical thymocytes reached the control values, while all the changes observed in the medulla of rats 3 days post castration, persisted. In addition, 7 days post castration, the volume of the interlobular connective tissue was increased and this persisted at day 15 post castration. The results indicate that orchidectomy can affect the thymic structure, and possibly the process of intrathymic T cell maturation; the extent of changes depending on the duration of the gonadal deprivation.