| Summary: | 碩士 === 國立陽明大學 === 生理學研究所 === 94 === Follicle-stimulating hormone (FSH), a pituitary hormone critically regulates ovarian folliculogenesis, stimulates granulosa cell proliferation and differentiation, and these actions are enhanced by ovarian factor transforming growth factor β (TGFβ). Till now, little is known regarding the molecular mechanism(s) whereby TGFβ synergizes FSH action to induce granulosa cell differentiation. The canonical and best characterized signaling pathway of TGFβ is mediated by ALK5/Smad2/3. Currently, an alternative lateral signaling pathway of TGFβ is through ALK1/Smad1 pathway and NFκB. Therefore, the objective of the present study was to investigate the participation of these two pathways in TGFβ1 enhancement on FSH-induced steroidogenesis in rat granulosa cells. TGFβ1 plus FSH dramatically induced the phosphorylation activation of Smad2 and Smad3 within 0.5 h to 1 h, and activating state declined to basal levels at 24 h and 48 h. Interestingly, TGFβ1 plus FSH increased Smad2/3 phosphorylation with greater potency than TGFβ1 alone. Also, a specific inhibitor of TβRI, SB431542 blocked TGFβ1-induced activation of Smad2 and 3, and this is consistent to our previous observation in TGFβ1 enhancement of FSH-induced steroidogenesis. Additionally, a specific NFκB inhibitor, SN50 dose-dependently elevated the FSH plus TGFβ1-stimulated progesterone production, and increased P450scc enzyme level. Together, this study demonstrates for the first time that FSH enhances the TGFβ1 signaling through TβRI-induced phosphorylation activation of Smad2 and 3 in rat ovarian granulosa cells. And NFκB activation opposes the Smad2/3 positive regulation of FSH plus TGFβ1-induced steroidogenesis in rat granulosa cells.
|
|---|
