Transforming Growth Factor-β Potentiation of Follicle-Stimulating Hormone-Induced Deoxyribonucleic Acid Synthesis in Hamster Preantral Follicles is Mediated by a Latent Induction of Epidermal Growth Factor1

The mechanisms of transforming growth factor-beta (TGF-beta) potentiation of FSH action on follicular DNA synthesis in the hamster were investigated by use of TGF-beta (beta 1 and beta 2) and a potent epidermal growth factor (EGF)-specific polyclonal antibody. Preantral follicles at stages 1-6 and early antral follicles at stage 7 were enzymatically and mechanically isolated from adult golden hamsters on proestrus. Follicles were incubated in Dulbecco's modified Eagle's medium with ITS+ (6.25 micrograms insulin, 6.25 micrograms transferrin, 6.25 micrograms selenium, 1.25 mg BSA, and 5.35 micrograms linoleic acid/ml) hydrocortisone, and 1 microCi/ml [3H]thymidine. Follicles were exposed for 24 h to FSH (100 ng/ml), TGF-beta 1, and TGF-beta 2 (1 and 10 ng/ml), EGF antibody (50 microliters/ml), and TGF-alpha (50 ng/ml) under various experimental conditions. Both TGF-beta 1 and TGF-beta 2 significantly potentiated FSH-induced follicular DNA synthesis; however, the effect was drastically attenuated by EGF antibody. EGF antibody also inhibited FSH-induced follicular [3H]thymidine incorporation. TGF-beta 2 potentiation of FSH action was also significantly inhibited by a second dose of TGF-beta 2 when added 6 h after the beginning of culture; however, follicles at different stages responded differently to the second dose of TGF-beta 2. For example, when the second dose of TGF-beta 2 was added 14 h after the first dose, only the large preantral follicles at stages 4-6 were affected. Interestingly, the second dose of TGF-beta 2 also inhibited TGF-beta 2-induced DNA synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)