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【bio-news】发现男性避孕关键蛋白质
中国科学家在长久以来寻求的新型男性避孕药的研究方面取得了一项进展，他们发现了男性的一些关键蛋白可以抑制精子的制造，而且可能成为未来男性避孕药的新靶标。他们的研究将发表在美国化学会于10月3日出版的《蛋白质组研究杂志》月刊上。
沙家豪及其同事指出，科学家不理解男性性激素睾酮的一个效应——注射这种激素如何抑制了精子的制造。此前的研究表明注射用睾酮和一种称为左炔诺孕酮（LNG）的合成激素的联用几乎完全抑制了精子，在这项研究的基础上，这组科学家设法弄清激素如何影响睾丸制造精子的细胞。
在一项针对男性的新研究中，他们发现睾酮和左炔诺孕酮的联用改变了人体的31种蛋白质的制造，相比之下，只接受了睾酮的男性只有13种蛋白质的制造发生了变化。这组科学家发现了一些蛋白质，它们既可以作为新的男性避孕药的靶标，也可以作为治疗不育的药物的靶标。
J. Proteome Res. , 7 ( 9 ), 3984 – 3993 , 2008 . 10.1021/pr800259t
Web Release Date: August 15, 2008
Copyright © 2008 American Chemical Society
Proteomic Analysis of Testis Biopsies in Men Treated with Injectable Testosterone Undecanoate Alone or in Combination with Oral Levonorgestrel as Potential Male Contraceptive
Yugui Cui , Hui Zhu , Yefei Zhu , Xuejiang Guo ,Ran Huo ,Xinghai Wang , Jiansun Tong , Lixin Qian , Zuomin Zhou ,Yue Jia , Yan-he Lue , Amiya Sinha Hikim , Christina Wang , Ronald S. Swerdloff , and Jiahao Sha
Laboratory of Reproductive Medicine, Department of Histology and Embryology, and Center of Clinical Reproductive Medicine, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China, Department of Reproductive Medicine, Jiangsu Family Planning Research Institute, Nanjing 210036, China, Division of Endocrinology, Department of Medicine, Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute, Torrance, California 90502, and Jiangsu Provincial Center of Disease Control and Prevention, Nanjing 210009, China
Received April 8, 2008
Treatment with injectable testosterone undecanoate (TU) alone or in combination with oral levonorgestrel (LNG) resulted in marked decreases in sperm concentrations. In this study, we used proteomic analyses to examine the cellular/molecular events occurring in the human testis after TU or TU + LNG treatment. We conducted a global proteomic analysis of the human testicular biopsies before and at 2 weeks after TU alone or TU + LNG treatment. Proteins showing significant changes in expression were identified and analyzed. As a result, 17 and 46 protein spots were found with significant differential expression after the treatment with TU alone and TU + LNG, respectively. TU treatment changed the expression of heterogeneous nuclear ribonucleoprotein K (hnRNP K), proteasome inhibitor PI31 subunit (PSMF1), and superoxide dismutase [Mn] mitochondrial precursor (SOD2). These proteins inhibit “assembly”, induce cell death, and promote compensatory “cell survival” in the testis. After TU + LNG treatment, “proliferation/cell survival” and “apoptosis/death” were the predominant responses in the testis. TU + LNG treatment inhibited the expression of Prolyl 4-hydroxylase beta subunit (P4HB) and Annexin A2 (Annexin II). These proteins are involved in apoptosis and cell proliferation, respectively. TU + LNG treatment also enhanced the expression of SOD2 and Parvalbumin alpha (Pvalb). These two proteins may protect testicular cells against apoptosis/death and promote cell survival. In conclusion, TU and TU + LNG treatments suppress spermatogenesis through different pathways by changing the expression of different proteins. hnRNP K, PSMF1, SOD2, P4HB, Annexin II, and Pvalb, are key proteins that may be early molecular targets responsible for spermatogenesis suppression induced by hormone treatment.
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作者:admin@医学,生命科学 2010-10-14 17:11
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