Follistatin is a novel, 32kDa cysteine-rich, single-chain polypeptide, recently isolated and characterized by protein microsequencing, cDNA cloning and DNA sequencing. It specifically inhibits FSH release. We propose to study its physiological role in vivo and in vitro using monoclonal and/or polyclonal antibodies specific to follistatin. Several synthetic fragments of follistatin will be synthesized, conjugated carrier protein and used as antigens. Antisera so raised will be fully characterized and validated. Effects of follistatin on such processes as ovarian follicular maturation and testicular development will be studied using radioimmunoassays, immunohistochemistry, in situ hybridization and passive immunization. We will study the detailed effects of follistatin on the inhibition of FSH release under normal and various altered reproductive conditions. We will also attempt to use immunoaffinity purified follistatin to disrupt follicular development and ovulation by decreasing of blocking secretion of FSH. If this will be achieved, we will attempt to reverse this by administration of antibodies specific to follistatin. In this way, we propose to elucidate the interactions among the gonadotropins, steroids and the follistatin in the functions of reproductive system.
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