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Analysis of androgenic effects in Sertoli cells during spermatogenesis

精子发生过程中支持细胞的雄激素作用分析

基本信息

批准号：
16591693
负责人：
KOMORI SHINJI
金额：
$ 2.24万
依托单位：
HYOGO COLLEGE OF MEDICINE
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591693/
关键词：
androgen androgen receptor spermatogenesis Sertoli cell Translationally controlled tumor protein 生殖細胞

项目摘要

Androgens are important factors in spermatogenesis. However, the biological role of androgen in Sertoli cells is still unclear. In this study, we analyzed mutations and CAG repeats of the androgen receptor gene in 19 azoospermic and 117 oligozoospermic men. No mutations were identified, but 9 of 117 oligozoospermic men were found to carry 14 or 15 CAG repeats, as compared to more than 16 CAG repeats in 136 normal fertile men analyzed. Analysis of the androgenic effect on the expression of transition protein 1 and 2 (TP1, 2) by co-transfection experiments showed that androgens regulate the transcription of TP1 via a Dfd-like molecules and the transcription of TP2 via androgen -androgen receptor complex, respectively. We analyzed the effect of dihydrotestosterone (DHT) on protein profiles in the TM4 mouse Sertoli cell line using SELDI-TOF mass spectrometry. DHT increased the expression of seven proteins of 4.3, 5.0, 5.7, 5.8, 10.0, 10.0 and 11.3kDa and decreased six proteins of 4.9, 5.0, 6.3, 8.6, 12.4 and 19.8 kDa. One of decreased molecule (19.8 kDa) is identified to be a translationally controlled tumor protein. These results show that androgen affects the spermatogenesis in both germ cells and Sertoli cells.

雄激素是影响精子发生的重要因素。然而，雄激素在支持细胞中的生物学作用仍不清楚。在这项研究中，我们分析了19名无精子症和117名少精子症男性雄激素受体基因的突变和CAG重复序列。没有发现突变，但117名少精子症患者中有9名携带14或15个CAG重复序列，相比之下，136名正常生育男性的CAG重复序列超过16个。通过共转染实验分析雄激素对过渡蛋白1和2(TP1，2)表达的影响，结果表明，雄激素分别通过DFD样分子调控TP1的转录，通过雄激素-雄激素受体复合体调控TP2的转录。我们用SELDI-TOF质谱仪分析了双氢睾酮(DHT)对TM4小鼠Sertoli细胞系蛋白质组分的影响。DHT可上调4.3、5.0、5.7、5.8、10.0、10.0和11.3 kDa的7种蛋白质的表达，降低4.9、5.0、6.3、8.6、12.4和19.8 kDa的6种蛋白质的表达。其中一个减少的分子(19.8 kDa)被鉴定为翻译控制的肿瘤蛋白。结果表明，雄激素对生殖细胞和支持细胞的精子发生均有影响。