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

Bakshi, RP and Galande, S and Bali, P and Dighe, R and Muniyappa, K (2001) Developmental and hormonal regulation of type II DNA topoisomerase in rat testis. In: Journal of Molecular Endocrinology, 26 (3). pp. 193-206.

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Type II DNA topoisomerase (topo II) is required for 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 development of postnatal testis and gametogenesis is unclear. Here, we report that rat testis topo II is developmentally and hormonally regulated. Topo $II \alpha \hspace{3mm} mRNA$ levels peaked prior to the onset of puberty, declined sharply thereafter and stabilized in adult testis. In contrast, topo II enzyme content was lesser 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 $II \alpha \hspace{3mm} mRNA$ levels in prepubertal testis, continued treatment failed to enhance topo $II \alpha \hspace{3mm} mRNA$ over postpubertal control levels. The extent of topo II activity remained steady regardless of the testosterone-induced increase in topo $II \alpha \hspace{3mm} mRNA$ levels. Inhibition of testosterone function in postpubertal animals by EDS and flutamide, resulted in significant decrease in topo IIa gene expression and topo II activity. Administration of exogenous T to EDS- and flutamide-treated rats restored topo $II \alpha \hspace{3mm} mRNA$ 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 separable from its effect on topo $II\alpha$ expression. Our results reveal that testosterone acts as a positive regulator of topo IIa gene expression and is required for the maintenance of topo $II\alpha$ expression during the development of postnatal testis and spermatogenesis.

Item Type: Journal Article
Publication: Journal of Molecular Endocrinology
Publisher: Society for Endocrinology
Additional Information: Copyright of this article belongs to Society for Endocrinology.
Department/Centre: Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Division of Biological Sciences > Biochemistry
Date Deposited: 23 Oct 2007
Last Modified: 19 Sep 2010 04:40
URI: http://eprints.iisc.ac.in/id/eprint/12260

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