Epidermal growth factor regulates the development of stem and progenitor Leydig cells in rats.

Epidermal growth factor (EGF) has many physiological roles. However, its effects on stem and progenitor Leydig cell development remain unclear. Rat stem and progenitor Leydig cells were cultured with different concentrations of EGF alone or in combination with EGF antagonist, erlotinib or cetuximab. EGF (1 and 10 ng/mL) stimulated the proliferation of stem Leydig cells on the surface of seminiferous tubules and isolated CD90(+) stem Leydig cells and progenitor Leydig cells but it blocked their differentiation. EGF also exerted anti-apoptotic effects of progenitor Leydig cells. Erlotinib and cetuximab are able to reverse EGF-mediated action. Gene microarray and qPCR of EGF-treated progenitor Leydig cells revealed that the down-regulation of steroidogenesis-related proteins (Star and Hsd3b1) and antioxidative genes. It was found that EGF acted as a proliferative agent via increasing phosphorylation of AKT1. In conclusion, EGF stimulates the proliferation of rat stem and progenitor Leydig cells but blocks their differentiation.