Multifactorial regulation of DNA synthesis in goldfish ovarian follicles

The present study examines the interactive effects of epidermal growth factor (EGF) and transforming growth factor-alpha (TGF alpha) with insulin, insulin-like growth factors I and II (IGF-I and IGF-II), and human chorionic gonadotropin (hCG) on DNA synthesis by goldfish ovarian follicles in vitro. DNA synthesis was assessed from the incorporation of [3H]thymidine. When tested individually, EGF, TGF alpha, insulin, IGFs, and hCG enhanced DNA synthesis by vitellogenic ovarian follicles. The interactive effects of EGF and TGF alpha on DNA synthesis by vitellogenic follicles were not additive, suggesting that these growth factors work through the same receptors. The most profound mitogenic effects of EGF and TGF alpha were seen when they were combined with insulin, IGF-I, or IGF-II. Unlike IGF-1, which had an additive effect when tested with hCG, EGF and hCG effects on DNA synthesis were not additive. Treatment with an antibody to EGF but neither gamma-globulin nor IGF-I antibody blocked the stimulatory actions of hCG on DNA synthesis by vitellogenic follicles. This suggests that EGF mediates the actions of hCG on DNA synthesis. In summary, these data support the concept that several growth factors and gonadotropins participate in the regulation of DNA synthesis in goldfish vitellogenic follicles.