Ovary

Sequential Gonadotropin Treatment of Immature Mice Leads to Amplification of Transforming Growth Factor Action, Via Up-Regulation of Receptor-Type 1, Smad 2 and 4, and Down-Regulation of Smad 6

Abstract
The present study was designed to establish the cellular localization and expression of transforming growth factor (TGF) signaling pathway components, including TGF1 and 2, TGF receptors type I (TRI) and II (TRII), and Smads 2, 3, 4, and 6, during gonadotropin-induced follicular maturation and ovulation in the mouse ovary. Immature 21- day-old mice were sequentially treated with recombinant human FSH (r-hFSH), 5 IU daily for 3 days, and hCG once at Day 24 of life. Immunohistochemical experiments revealed a TGF1 staining in granulosa cells (GC) and theca interna cells (TIC) as well as in oocytes, whereas that of TGF2 was mainly localized in oocytes and GC. A strong immunostaining for both T- RI and -RII was observed in the TIC and, in a lesser extent, in GC. Whereas oocytes did not exhibit any staining for T-RII, their T-RI immunostaining was strong. Smads were detected in oocytes, GC, and luteal cells and in a lesser amount in TIC; the immunostaining for Smad 4 was the strongest. Western blotting and RT-PCR analyses indicated that in response to gonadotropins, TGF2, T-RI, Smad 2 and Smad 4 mRNA and protein levels increased, while those of Smad 6 decreased in ovarian homogenates. In conclusion, these results show that in a model of immature mouse exposed to a sequential gonadotropin treatment, FSH and LH increased the expression of the TGF& [beta] signaling system through the increase of TGF2, TRI, stimulatory Smad 2 and common Smad 4 expression, occuring concomitantly with a decrease of the inhibitory Smad 6 expression.

Key words: Ovary • Follicle • Follicle-stimulating hormone • Growth factors • Luteinizing hormone

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