Abstract
BackgroundThe 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.ResultsIn 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.ConclusionsGDNF stimulates the proliferation of ISCs via its receptor subunit NCAM and the consequent activation of the ERK1/2 signaling pathway.
Highlights
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) stimulates the proliferation of mouse immature Sertoli cells (ISCs) Highly purified ISC cultures from 4-5-day-old mice were acquired through several passages of testicular cells, which were maintained in serum-free DMEM/F12 medium
To test whether GDNF affects the proliferation of ISCs, GDNF (20 ng/ml) was added into the culture medium, and the proliferation of ISCs was evaluated by BrdU incorporation
Summary
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-b superfamily, and its receptor subunits GDNF family receptor alpha 1 (GFRa1), 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). The expression patterns of these receptor subunits and the downstream signaling pathways have not been addressed in ISCs. Sertoli cells secrete growth factors to regulate the proliferation and differentiation of germ cells and themselves [1]. Sertoli cells secrete growth factors to regulate the proliferation and differentiation of germ cells and themselves [1] One such factor is glial cell line-derived neurotrophic factor (GDNF), a distantly related member of the transforming growth factor-b (TGF-b) superfamily [2,3,4,5]. GFRa1- and RET-null mice exhibit similar phenotypes as GDNF-null mice and die during the
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