Paracrine regulation of reproductive system by TGFbeta superfamily

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Recently, the evidence has been accumulated that transforming growth factor- (TGF) beta superfamily growth factors play indispensable roles for differentiation, cell proliferation or expression of the function of various tissues. In this research project, we focused on the physiological roles of TGFbeta superfamily growth factors and related peptides in reproductive system. The summary of the results are as follows :1) We found that activin release "2-cell block" during early embryogenesis and enhance embtyo development in mice. Immunohistochemical analysis and in situ hybridization technique to detect mRNA revealed that activin is synthesized both in the embryo and the oviduct. Activin receptor mRNA was detected in embryos but not in oviductal cells. These results suggest that activin is an autocrine factor to promote embryo development and oviductal cells help its growth by supplying additional activin.2) The mode of action of activin to regulate gonadotropin-secreting-cells in the p … More ituitary was investigated. Activin increased the number of follicle stimulating hormone secreting-cells specifically. Furthermore, it was found that folliculo-stelate cells in the pituitary secrete follistatin and this peptide regulate activin's paracrine/autocrine action by inhibiting its bioactivity.3) TGFbeta was found to be a paracrine factor from macrophage to mediate prolactin action maintaining luteal progesterone secretion in rats. We also succeeded in isolating and characterizing the cDNA of 20alpha-hydroxysteroid dehydrogenase, which is one of the target proteins which expression are regulated by TGFbeta in the ovary.4) We succeeded in producing specific antibodies to activin/inhibin betaA and betaB subunits, inhibin alpha subunits, and follistain. Using these antibodies we established immunoassay system for these bioactive polypeptides.5) We Succeeded in isolating cDNA clone of equine avtivin/inhibin betaA subunit. Cloning of equine betaB or alpha subunits, follistatin is also now under way. Less