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柠檬酸他莫昔芬对雄性大鼠核染色质浓缩过程中基因表达的影响。

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

作者信息

Aleem Mukhtar, Padwal Varsha, Choudhari Jyoti, Balasinor Nafisa, Parte Priyanka, Gill-Sharma Manjeet

机构信息

Department of Neuroendocrinology, National Institute for Research in Reproductive Health (ICMR), J. M. Street, Parel, Mumbai 400012, India.

出版信息

Asian J Androl. 2005 Sep;7(3):311-21. doi: 10.1111/j.1745-7262.2005.00027.x.

DOI:10.1111/j.1745-7262.2005.00027.x
PMID:16110360
Abstract

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 kg/(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-tau (CREMtau), androgen-binding 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 CREMtau 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 CREMtau 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 CREMtau involved in chromatin condensation during spermiogenesis. Tamoxifen citrate affects the expression of these genes at both the transcriptional and post-transcriptional levels.

摘要

目的

评估柠檬酸他莫昔芬对雄性大鼠核染色质凝聚过程中基因表达的影响。

方法

在成年雄性大鼠暴露60天后,评估口服剂量为0.4 kg/(kg·d)的柠檬酸他莫昔芬对体外染色质解聚速率、吖啶橙(AO)染料摄取、巯基浓度、过渡蛋白1、2(TP1、TP2)、鱼精蛋白1(P1)、环磷酸腺苷反应元件调节剂-tau(CREMtau)、雄激素结合蛋白(ABP)和环磷酸腺苷(cAMP)水平及/或表达的影响。对照组给予赋形剂。

结果

柠檬酸他莫昔芬提高了附睾头精子的染色质解聚速率,增加了AO染料摄取,降低了游离巯基水平,并降低了睾丸中TP1、TP2、P1和CREMtau的水平,而cAMP未受影响。精子中不存在P1沉积。睾丸中TP1、TP2的转录本增加,P1和ABP的转录本减少,而CREMtau的转录本未受影响。

结论

柠檬酸他莫昔芬通过降低睾丸中参与精子发生过程中染色质凝聚的蛋白质TP1、TP2、P1和CREMtau的水平,降低了附睾头精子染色质的紧实度。柠檬酸他莫昔芬在转录和转录后水平上影响这些基因的表达。

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