Insights into the role of androgen receptor in human testicular peritubular cells
Insights into the role of androgen receptor in human testicular peritubular cells
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深入了解雄激素受体在人睾丸管周细胞中的作用
DOI：
10.1111/andr.12509
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发表时间：
2018
期刊：
影响因子：
4.5
通讯作者：
Artur Mayerhofer
中科院分区：
文献类型：
--
作者：
C. Mayer;Marion Adam;Marion Adam;Lena Walenta;N. Schmid;Hanna Heikelä;K. Schubert;F. Flenkenthaler;K. Dietrich;S. Gruschka;G. Arnold;Thomas Fröhlich;J. Schwarzer;F. Köhn;L. Strauss;H. Welter;Matti Poutanen;Artur Mayerhofer
收缩性平滑肌样管周细胞构建男性曲细精管壁。它们对精子运输至关重要，并通过分泌因子（包括胶质细胞源性神经营养因子）补充支持细胞的功能。先前的研究表明，它们还分泌趋化因子C-X-C基序趋化因子配体12（CXCL 12），其在精子发生中具有已知的作用。管周细胞表达雄激素受体（AR），其保留在分离的人睾丸管周细胞中。我们的目的是探索人类睾丸管周细胞中AR调节的功能。考虑到不育男性通常具有高芳香化酶活性，这可能会降低睾丸内雄激素浓度，因此研究了男性不育的动物模型。这些小鼠由于高芳香化酶活性而显示出精子发生的年龄依赖性损失。将人睾丸管周细胞暴露于双氢睾酮或抗雄激素氟替卡松。我们研究了AR、平滑肌细胞标志物、胶质细胞系源性神经营养因子和15种先前鉴定的分泌因子，包括CXCL 12。我们使用qPCR、Western印迹、ELISA或选择性反应监测（SRM）。在雄性不育的动物模型中，我们采用qPCR和免疫组织化学。双氢睾酮增加AR和氟替卡松阻止这些行动。平滑肌细胞标志物钙调蛋白和平滑肌肌动蛋白也增加，而细胞大小或细胞增殖没有变化。二氢睾酮不增加胶质细胞系源性神经营养因子或CXCL 12的分泌，但增加丝氨酸蛋白酶抑制剂（SERPIN）E1的水平。具有高芳香化酶活性的男性不育动物模型显示AR免疫反应性睾丸管周细胞数量减少，表明雄激素和/或雌激素水平的改变可能影响管周细胞中AR介导的反应。雄激素作用于人睾丸管周细胞以增强AR水平、其收缩表型并调节一些分泌因子的分泌。这项研究表明，人类肾小管周细胞功能的某些方面受到雄激素的调节。
Contractile smooth muscle‐like peritubular cells build the wall of seminiferous tubules in men. They are crucial for sperm transport and complement the functions of Sertoli cells by secreting factors, including glial cell line‐derived neurotrophic factor. Previous studies revealed that they also secrete the chemokine C‐X‐C motif chemokine ligand 12 (CXCL12), which has known roles in spermatogenesis. Peritubular cells express the androgen receptor (AR), which is retained in isolated human testicular peritubular cells. We aimed to explore AR‐regulated functions in human testicular peritubular cells. Bearing in mind that infertile men often have high aromatase activity, which may lower intratesticular androgen concentrations, an animal model for male infertility was studied. These mice display an age‐dependent loss in spermatogenesis due to high aromatase activity. Human testicular peritubular cells were exposed to dihydrotestosterone or the antiandrogen flutamide. We studied AR, smooth muscle cell markers, glial cell line‐derived neurotrophic factor and 15 secreted factors previously identified, including CXCL12. We used qPCR, Western blotting, ELISA or selected reaction monitoring (SRM). In the animal model for male infertility, we employed qPCR and immunohistochemistry. Dihydrotestosterone increased AR and flutamide prevented these actions. The smooth muscle cell markers calponin and smooth muscle actin were likewise increased, while cell size or cellular proliferation was not changed. Dihydrotestosterone did not increase glial cell line‐derived neurotrophic factor or CXCL12 secretion but increased levels of serine proteinase inhibitor (SERPIN) E1. The animal model for male infertility with high aromatase activity showed reduced numbers of AR‐immunoreactive testicular peritubular cells, suggesting that altered androgen and/or oestrogen levels could influence AR‐mediated responses in peritubular cells. Androgens act on human testicular peritubular cells to enhance AR levels, their contractile phenotype and to modulate the secretion of some secreted factors. This study suggests that some aspects of human peritubular cell functions are regulated by androgens.
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影响因子：
4.6
作者：
Windschüttl S;Kampfer C;Mayer C;Flenkenthaler F;Fröhlich T;Schwarzer JU;Köhn FM;Urbanski H;Arnold GJ;Mayerhofer A
通讯作者：
Mayerhofer A
血管紧张素II通过AT1受体调节睾丸管周细胞功能：男性不育的特殊情况
影响因子：
4.1
作者：
Welter H;Huber A;Lauf S;Einwang D;Mayer C;Schwarzer JU;Köhn FM;Mayerhofer A
通讯作者：
Mayerhofer A
影响因子：
4.8
作者：
K. Wiren;Xiao Wei Zhang;Chawnshang Chang;Edward J. Keenan;E. S. Orwoll
通讯作者：
K. Wiren;Xiao Wei Zhang;Chawnshang Chang;Edward J. Keenan;E. S. Orwoll
影响因子：
4.4
作者：
Flenkenthaler, Florian;Windschuettl, Stefanie;Arnold, Georg J.
通讯作者：
Arnold, Georg J.
不育患者睾丸管周细胞收缩标记蛋白部分缺失
影响因子：
4.5
作者：
Welter H;Kampfer C;Lauf S;Feil R;Schwarzer JU;Köhn FM;Mayerhofer A
通讯作者：
Mayerhofer A