|Budget Amount *help
¥1,900,000 (Direct Cost : ¥1,900,000)
Fiscal Year 1995 : ¥400,000 (Direct Cost : ¥400,000)
Fiscal Year 1994 : ¥1,500,000 (Direct Cost : ¥1,500,000)
Fallopian tube represents an important microenvironment for an early embryo, it has a role in early embryo development. We have reported that epidermal growth factor (EGF) and transforming growth factor (TGF) alpha are present in human fallopian tube epithelium that are involved in early embryo development. In this study, we have shown that these factors are expressed in tubal epithelial cells specifically to the menstrual cycle stages : their amounts were in proportion to the serum estradiol levels. Furthermore, we examined if estrogen induces these factors locally. Estradiol treatment of postmenopausal women significantly increased the gene expression of EGF receptors and its ligands in tube epithelial cells. Estrogen also exhibited a similar effect on the cultured tubal cells. These data suggested that estrogen directly induces the EGF,TGFalpha/EGF receptor autocrine mechanism in human fallopian tube epithelial cells both in vivo and in vitro.
We next examined the biological signific
ance of estrogen inducible autocrine mechanism. It is well known that the endometrial epithelium proliferates in response to estrogen, and estrogen also proliferated fallopian tube epithelium. We tested if the local autocrine mechanism mediates the estrogen-induced tube epithelial cell growth. If the mechanism mediates the estrogen action, then the blockage of the autocrine mechanism should suppress the estrogen-induced cell growth. As expectedly, anti-EGF and -EGF receptor monoclonal neutralizing antibodies significantly inhibited the estrogen induced tubal cell growth in vitro. However, anti-TGFalpha antibody failed to show the effect. The data were confirmed by the fact that EGF but not TGFalpha could restore the growth-inhibition by anti-EGF.
All these results indicate that there present a EGF and TGFalpha autocrine mechanism in human fallopian tube epithelial cells. EGF and TGFalpha play a role in early embryo development, and, at a same time, the local autocrine mechanism is important in mediating the estrogen induced cell growth. Less