Opposing actions of TGFβ and MAP kinase signaling in undifferentiated hen granulosa cells

The present studies were conducted to establish interactions between transforming growth factor (TGF)-β and the epidermal growth factor (EGF) family members, TGFα and betacellulin (BTC), relative to proliferation and differentiation of granulosa cells in hen ovarian follicles. Results presented demonstrate expression of TGFβ isoforms, plus TGFα, BTC, and ErbB receptors in prehierarchal follicles, thus establishing the potential for autocrine/paracrine signaling and cross-talk within granulosa cells at the onset of differentiation. Treatment with TGFα or BTC increases levels of TGFβ1 mRNA in undifferentiated granulosa cells, while the selective inhibitor of mitogen activated protein kinase signaling, U0126, reverses these effects. Moreover, TGFβ1 attenuates c-myc mRNA expression and granulosa cell proliferation, while TGFα blocks both these inhibitory effects. Collectively, these data provide evidence that EGF family ligands regulate both the expression and biological actions of TGFβ1 in hen granulosa cells, and indicate that the timely interaction of these opposing factors is an important modulator of both granulosa cell proliferation and differentiation.