Transforming growth factor-alpha stimulates proliferation of rat Sertoli cells

The number of Sertoli cells is positively correlated with the number of germ cells produced in the testis, but the regulation of Sertoli cell proliferation and final density is poorly understood. Using non-aggregated Sertoli cells from 8 to 9-day-old rat testes, highly enriched by lectin binding, we explored effects of Sertoli cell growth factor candidates in vitro. Proliferation was assessed by 3H-thymidine incorporation, bromodeoxyuridine labeling and supravital staining, and FSH was used as positive control. Transforming growth factor-alpha (TGF-alpha) was found to stimulate Sertoli cell proliferation in a dose-dependent manner. Epidermal growth factor (EGF) and betacellulin mimicked the effect, demonstrating specificity of the response as they share receptors with TGF-alpha. Insulin-like growth factor I and II, acidic and basic fibroblast growth factor and stem cell factor lacked significant stimulatory effects. We conclude that EGF/TGF-alpha is a growth factor for Sertoli cells in vitro, possibly contributing to paracrine regulation of Sertoli cell proliferation in vivo.