NGF induces adult stem Leydig cells to proliferate and differentiate during Leydig cell regeneration.
NGF induces adult stem Leydig cells to proliferate and differentiate during Leydig cell regeneration.
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DOI：
10.1016/j.bbrc.2013.05.098
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发表时间：
2013-06
影响因子：
3.1
通讯作者：
Lei Zhang;Huaxi Wang;Yan Yang;Hui Liu;Qi‐hao Zhang;Q. Xiang;R. Ge;Zhijian Su;Yadong Huang-
中科院分区：
文献类型：
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作者：
Lei Zhang;Huaxi Wang;Yan Yang;Hui Liu;Qi‐hao Zhang;Q. Xiang;R. Ge;Zhijian Su;Yadong Huang-
神经生长因子（NGF）已被报道参与男性生殖生理。然而，很少有报道描述了神经生长因子在睾丸间质细胞发育过程中的活性。本研究的目的是研究神经生长因子在干细胞间质细胞（SLC）再生过程中的作用。我们研究了NGF对睾丸间质细胞（LC）再生的影响，通过测量mRNA水平在成年大鼠睾丸后乙烷二甲磺酸盐（EDS）处理。此外，我们还利用建立的大鼠曲细精管器官培养模型，通过EdU染色、实时荧光定量PCR和蛋白质印迹法研究了NGF对SLC增殖和分化的调控作用。同时，以睾丸间质祖细胞（PLCs）和未成熟Leydig细胞（ILC）为实验材料，研究了NGF对不同发育阶段LCs的影响。在体内Leydig细胞再生过程中，NGF mRNA水平发生显著变化。在体外实验中，NGF可显著促进睾丸间质干细胞的增殖，并诱导类固醇生成酶基因和3β-HSD蛋白的表达。结果表明，NGF可提高PLC和ILC中Cyclin D1和Hsd 17 b3 mRNA的表达水平，并可提高ILC中Cyclin D1 mRNA的表达水平。这些结果表明，在LC再生过程中，NGF可能发挥重要作用，通过调节不同发育阶段的LC的增殖和分化，从SLCs到PLCs和从PLCs到ILC。NGF对睾丸间质细胞的这种作用的发现将为开发PADAM（Partial Androgen Deficiency in the Aging Male）的新的潜在治疗方法提供有用的信息。
Nerve growth factor (NGF) has been reported to be involved in male reproductive physiology. However, few reports have described the activity of NGF during Leydig cell development. The objective of the present study was to examine the role of NGF during stem-Leydig-cell (SLC) regeneration. We investigated the effects of NGF on Leydig-cell (LC) regeneration by measuring mRNA levels in the adult rat testis after ethane dimethanesulfonate (EDS) treatment. Furthermore, we used the established organ culture model of rat seminiferous tubules to examine the regulation of NGF during SLC proliferation and differentiation using EdU staining, real-time PCR and western blotting. Progenitor Leydig cells (PLCs) and immature Leydig cells (ILCs) were also used to investigate the effects of NGF on LCs at different developmental stages. NGF mRNA levels changed significantly during Leydig-cell regeneration in vivo. In vitro, NGF significantly promoted the proliferation of stem Leydig cells and also induced steroidogenic enzyme gene expression and 3β-HSD protein expression. The data from PLCs and ILCs showed that NGF could increase Cyclin D1 and Hsd 17b3 mRNA levels in PLCs and Cyclin D1 mRNA levels in ILCs. These results indicate that NGF may play an important role during LC regeneration by regulating the proliferation and differentiation of LCs at different developmental stages, from SLCs to PLCs and from PLCs to ILCs. The discovery of this effect of NGF on Leydig cells will provide useful information for developing new potential therapies for PADAM (Partial Androgen Deficiency in the Aging Male).