Department of Cell Biology, College of Life Science and Technology, Jinan University, 510632 Guangzhou, PR China.
Biochem Biophys Res Commun. 2013 Jun 28;436(2):300-5. doi: 10.1016/j.bbrc.2013.05.098. Epub 2013 Jun 4.
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).
神经生长因子（NGF）已被报道参与男性生殖生理过程。然而，鲜有报道描述了 NGF 在睾丸间质细胞（Leydig 细胞）发育过程中的作用。本研究旨在探讨 NGF 在始基-Leydig 细胞（SLC）再生过程中的作用。我们通过检测乙基亚硝脲（EDS）处理后成年大鼠睾丸中 NGF 的 mRNA 水平，研究了 NGF 对 Leydig 细胞（LC）再生的影响。此外，我们利用大鼠生精小管的已建立器官培养模型，通过 EdU 染色、实时 PCR 和 Western blot 检测，研究了 NGF 在 SLC 增殖和分化过程中的调控作用。祖细胞 Leydig 细胞（PLCs）和未成熟 Leydig 细胞（ILCs）也被用于研究 NGF 对不同发育阶段 LC 的作用。NGF mRNA 水平在体内 Leydig 细胞再生过程中发生显著变化。在体外，NGF 显著促进了 SLC 的增殖，并诱导了类固醇生成酶基因的表达和 3β-HSD 蛋白的表达。来自 PLCs 和 ILCs 的数据表明，NGF 可以增加 PLCs 中的 Cyclin D1 和 Hsd17b3 mRNA 水平，以及 ILCs 中的 Cyclin D1 mRNA 水平。这些结果表明，NGF 可能通过调节不同发育阶段（从 SLC 到 PLC 和从 PLC 到 ILC）LC 的增殖和分化，在 LC 再生过程中发挥重要作用。NGF 对 Leydig 细胞的这种作用的发现，将为开发治疗部分雄激素缺乏症（PADAM）的新潜在疗法提供有用信息。
