Yang Yongguang, Han Chunsheng
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100080, China.
BMC Cell Biol. 2010 Oct 18;11:78. doi: 10.1186/1471-2121-11-78.
The proliferation and final density of Sertoli cells in the testis are regulated by hormones and local factors. Glial cell line-derived neurotrophic factor (GDNF), a distantly related member of the transforming growth factor-β superfamily, and its receptor subunits GDNF family receptor alpha 1 (GFRα1), RET tyrosine kinase, and neural cell adhesion molecule (NCAM) have been reported to be expressed in the testis and involved in the regulation of proliferation of immature Sertoli cells (ISCs). However, the expression patterns of these receptor subunits and the downstream signaling pathways have not been addressed in ISCs.
In the present study, we have reported that the proliferation of cultured ISCs was significantly enhanced by GDNF. The receptor subunits GFRα1 and NCAM but not RET were expressed in ISCs, and the stimulatory effect of GDNF on the proliferation of ISCs was significantly reduced by anti-NCAM antibody blocking or siRNA that specifically targets NCAM mRNA. Additionally, the ERK1/2 inhibitor, PD98059, completely abolished the mitogenic effect of GDNF on ISCs.
GDNF stimulates the proliferation of ISCs via its receptor subunit NCAM and the consequent activation of the ERK1/2 signaling pathway.
睾丸中支持细胞的增殖和最终密度受激素和局部因子调控。胶质细胞系源性神经营养因子（GDNF）是转化生长因子-β超家族中关系较远的成员，其受体亚基胶质细胞系源性神经营养因子家族受体α1（GFRα1）、RET酪氨酸激酶和神经细胞黏附分子（NCAM）已被报道在睾丸中表达，并参与未成熟支持细胞（ISC）增殖的调控。然而，这些受体亚基的表达模式以及ISC中的下游信号通路尚未得到研究。
在本研究中，我们报道了GDNF显著增强了培养的ISC的增殖。受体亚基GFRα1和NCAM在ISC中表达，而RET不表达，抗NCAM抗体阻断或特异性靶向NCAM mRNA的小干扰RNA（siRNA）显著降低了GDNF对ISC增殖的刺激作用。此外，细胞外信号调节激酶1/2（ERK1/2）抑制剂PD98059完全消除了GDNF对ISC的促有丝分裂作用。
GDNF通过其受体亚基NCAM以及随后ERK1/2信号通路的激活来刺激ISC的增殖。
