Epidermal growth factor and transforming growth factor-β modulation of follicle-stimulating hormone-induced deoxyribonucleic acid synthesis in hamster preantral and early antral follicles

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The interactions of epidermal growth factor (EGF) and transforming growth factor-β (TGF-β) in modulating FSH-induced follicular DNA synthesis were studied in isolated intact preantral (stages 1-6) and early antral (stage 7) ovarian follicles from adult hamsters. Follicles were exposed in vitro for 24 h to FSH (100 ng), EGF (50 ng), TGF-β1 (1-10 ng), or TGF-β2 (1-10 ng), either alone or in combination. The rate of DNA synthesis was assessed by measuring the incorporation of [3H]thymidine into follicular DNA. Both EGF and FSH significantly stimulated follicular DNA synthesis compared with that in controls. Both isoforms of TGF-β significantly increased follicular [3H]thymidine incorporation in a dose-dependent manner; the effect was greater for small preantral follicles, such as those of stages 1-4. Interestingly, TGF-β significantly inhibited EGF-induced follicular DNA synthesis, but the rates of DNA synthesis for most of the stages were still higher than that of the control follicles. Specificity of the TGF-β action on follicular DNA synthesis was evident from the ability of isoform-specific anti-TGF-β antibodies to neutralize the effect. These antibodies also reversed the TGF-β inhibition of EGF-induced DNA synthesis. Surprisingly, although TGF-β attenuated EGF-induced DNA synthesis, it synergized with FSH to stimulate follicular DNA synthesis. Interestingly, FSH-induced DNA synthesis remained unaffected by the anti-TGF-β antibodies, indicating that TGF-β may not mediate FSH action on follicular DNA synthesis. These studies suggest that a critical interaction of EGF and TGF-β modulates granulosa cell proliferation during folliculogenesis in the hamster. TGF-β may also influence FSH regulation of cell proliferation by lengthening the G1 phase of the granulosa cell cycle, thus recruiting more cells to enter the S phase when the preovulatory FSH surge acts on growing follicles.

Original languageEnglish (US)
Pages (from-to)552-557
Number of pages6
JournalBiology of reproduction
Issue number3
StatePublished - Mar 1 1993


ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology

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