Developmental and hormonal regulation of type II DNA topoisomerase in rat testis

Type II DNA topoisomerase (topo II) is required fur diverse biological functions including DNA replication, maintenance of genome stability, chromosome segregation and chromosome condensation. While the identity of topo II in rodent testis has been established, the regulation of topo II expression during the development of the postnatal testis and gametogenesis is unclear. Here, we report that rat testis topo II is developmentally and hormonally regulated. Topo II alpha mRNA levels peaked prior to the onset of puberty, declined sharply thereafter and stabilized in adult testis. III contrast, the topo II enzyme content was lon er in prepubertal testis but increased after. the onset of puberty. Topo II was expressed in a cell-specific manner within germ cells, being detected only in pachytene spermatocytes. While testosterone markedly increased topo II alpha mRNA levels in prepubertal testis, continued treatment failed to enhance topo II alpha mRNA above postpubertal control levels. The extent of topo II activity remained steady regardless of the trs testosterone-induced increase in topo II alpha mRNA levels. Inhibition of testosterone function in postpubertal animals by ethanedimethane sulphonate (EDS) and flutamide resulted in a significant decrease in topo II alpha. gene expression and topo II activity. The administration of exogenous testosterone (T) to EDS- and flutamide-treated rats restored topo IIa mRNA levels and topo II activity similar to the levels seen in the testis of age-matched control animals. Histochemical analyses of testes indicated that the effect of T on spermatogenesis was sepal-able from its effect on topo II alpha expression. Our results reveal that testosterone acts as a positive regulator of topo II alpha gene expression and is required for the maintenance of topo II alpha expression during the development of the postnatal testis and spermatogenesis.