INDUCTION OF IMMATURE THYMOCYTE PROLIFERATION AFTER CASTRATION OF NORMAL-MALE MICE

The physiological basis and immunological significance of thymic enlar gement in castrate male animals is not known. We used normal male C57 B1/6 mice to examine the contribution of in situ thymocyte proliferati on to castration-induced enlargement of the thymus. Animals castrated at 8-10 weeks of age were compared to normal intact males. Thymocytes were examined 4-120 days after castration using flow cytometry to dete rmine DNA content and thus the number of cells in active phases of the cell cycle. These properties were examined in unseparated thymocytes and in phenotypic subpopulations defined by expression of CD3, CD4, an d CD8. For thymocytes obtained from intact control glands, a mean of 1 1.0 +/- 1.0% were in active phases of the cell cycle. The percentage o f cycling thymocytes was increased to a mean of 22.5 +/- 1.9% in the w eek after castration (P < 0.001). This change occurred in the absence of significant thymic enlargement. At 8-10 days after castration, thym ic weight increased abruptly to a new steady state which was double th at of intact controls (78.0 +/- 4.1 vs. 39.1 +/- 2.6 mg; P < 0.001). I n these enlarged glands, only 9.9 +/- 0.8% of cells were cycling, whic h was not significantly different than controls (P > 0.3). Proliferati ng cells identified in fixed thymus tissue sections after in vivo admi nistration of bromodeoxyuridine were located in the subcapsular cortex and medulla. Analyses of thymocyte subpopulations indicated that most cycling cells had immature phenotypes (CD4(+)CD8(+), CD4(-)CD8(+), an d CD3(1o)or CD3(-)). Castrate glands studied in the steady state perio d 8-120 days after surgery contained significantly fewer CD3(+) cells than intact controls (P less than or equal to 0.045). The findings sug gest an intrathymic role for androgens in affecting generation of the mature T cell repertoire.