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The study was undertaken to further elucidate a role of gonadal hormones in maintenance of normal thymocyte maturation and sexual dimorphism in the intrathymic T-cell development. Rats of both sexes were gonadectomized or sham-gonadectomized (controls) at age of 2 and 6 months, and 30 days later the thymus size, cellularity and thymocyte composition were evaluated. In both control and gonadectomized rats, in spite of age, sexual dimorphism in the thymus size and cellularity was found. Gonadectomy in 2-month-old rats of both sexes increased the thymus cellularity, volumes of both cortex and medulla and thymus size (to a less extent in males), while in 6-month-old rats, in this respect, it was effective only in females. In ovariectomized (OVX) rats the increase in volume of cortex was more marked in younger rats, while that of medulla did not differ between rats of different age. It seems obvious that in both groups of OVX rats the volume of medullary non-lymphoid component was enlarged (the increase in medullary volume was more pronounced than that in its cellularity). Unlikely, in rats orchidectomized (ORX) at age of 2 months the volume of this component was either decreased or unaltered (the increase in the volume of medulla was less conspicuous than that in the number of medullary thymocytes). In control and gonadectomized rats of both ages, sexual dimorphism in the composition of thymocyte subsets was also observed. Gonadectomy in 2-month-old rats affected distinct stages of thymocyte maturation in male (increased the relative proportions of CD4+8+TCRαβlowcells and their CD4–8+TCRαβlowprecursors and decreased those of the most mature CD4+8-TCRαβhighand CD4–8+TCRαβhighcells) and female rats (decreased only the percentage of the least mature CD4–8-TCRαβ-cells). In older rats only ovariectomy had impact on the relative proportion of thymocytes decreasing, besides the relative proportion of CD4–8-TCRαβ-cells, those of CD4–8+TCRαβ-, CD4–8+TCRαβlow, positively selected CD4+8+TCRαβhighand the most mature CD4+8-TCRαβhigh, CD4–8+TCRαβhighcells and exerting an opposite effect on the percentages of CD4+8+TCRαβ-and CD4+8+TCRαβlowcells. Thus, results showed sex- and age-dependent changes in sensitivity of both the developing thymocytes and non-lymphoid cells to long-lasting gonadal deprivation.

The thymus structure, expression of CD4/CD8/TCR alpha beta on thymocytes and thymocyte proliferative and apoptotic indexes were analyzed in sexually immature 30-day-old and in sexually mature 60-day-old female rats neonatally androgenized (NA) by subcutaneous injection of 500 mu g testosterone propionate/day on days 1-3 and in their vehicle-administered counterparts. The treatment affected normal thymus development. Thus, at 30 days of age, there was a reduction in the thymus weight, reflecting a decrease in the main thymic compartments. However, at 60 days of age, thymus weight did not significantly differ from that in age-matched controls, since the cortical volume enlargement was followed by a proportional decrease in the medullary volume. In rats of both ages, the changes in thymic compartments most likely reflected alterations in the size of both lymphoid and nonlymphoid components. Furthermore, in NA rats, substantial changes in thymocyte phenotypic characteristics were registered, in spite of their age. In both groups of NA rats, a decrease in the relative proportion of the least mature CD4-8-TCR alpha beta- cells and in that of CD4+8- TCR alpha beta-/TCR alpha beta(low) cells followed by an increase in the percentage of their successor CD4+8+TCR alpha beta-/TCR alpha beta(low) cells was detected. In addition, in 30-day-old NA rats, the relative proportions of CD4+8+TCR alpha beta(high) cells ( just positively selected) and that of mature single positive (CD4+8- and CD4-8+) and CD4-8- double negative TCR alpha beta(high) cells, were reduced, while in 60-day-old NA rats only the percentage of CD4+8+TCR alpha beta(high) thymocytes was decreased. Thus, the study showed that the changes in the development of the hypothalamo-pituitary-gonadal axis induced by neonatal androgenization may affect the thymus development and intrathymic T-cell maturation. Copyright (C) 2005 S. Karger AG, Basel.