Effects of tamoxifen citrate on gene expression during nuclear chromatin condensation in male rats

Aim： To evaluate the effects of tamoxifen citrate on gene expression during nuclear chromatin condensation in male rats. Methods： The effects of an oral dose of 0.4 mg/（kg·d） tamoxifen citrate on rates of in vitro chromatin decondensation, acridine orange （AO） dye uptake, concentration of thiol-groups, levels and/or expression of transition proteins 1, 2 （TP1, TP2）, protamine 1 （P1）, cyclic AMP response element modulator-τ （CREMτ）, androgenbinding protein （ABP） and cyclic adenosine 3＇, 5＇ monophosphate （cAMP） were evaluated after 60 days of exposure in adult male rats. Controls received the vehicle. Results： Tamoxifen citrate enhanced the rates of chromatin decondensation, increased AO dye uptake and reduced free thiols in caput epididymal sperms and reduced the levels of TP1, TP2, P1, and CREMτ in the testis, while cAMP was unaffected. P1 deposition was absent in the sperm. The transcripts of TP1, TP2 were increased, of P1 and ABP decreased, while those of CREMτ unaffected in the testis. Conclusion： Tamoxifen citrate reduced caput epididymal sperm chromatin compaction by reducing the testicular levels of proteins TP1, TP2 and P1 and the CREMτ involved in chromatin condensation during spermiogenesis. Tamoxifen citrate affects the expression of these genes at both the transcriptional and post-transcriptional levels. （Asian J Androl 2005 Sep; 7： 311-321）