Recent research in reproductive endocrinology has demonstrated the importance of follicle stimulating hormone (FSH) in the regulation of gametogenesis and gonadal steroid production. It has been shown that N-linked oligosaccharides, attached to asparagine residues at specific sites along the molecule, are essential for post-receptor target cell activation but not receptor binding. These sugars also play a role in determining the half-life of the molecule in circulation. We plan to use the technique of site-directed mutagenesis to produce a recombinant human FSH molecule that will have one or more of the asparagine residues replaced with a similarly charged amino acid to """"""""erase"""""""" the site of N-linked sugar attachment. Preliminary studies have shown that removal of sugars from the alpha chain severely decrease biologic activity. Removal of these sugar residues, by mutagenesis, will produce a long acting competitive antagonist of FSH, which, when administered to humans, would be expected to result in an anovulatory state or azospermia. A mutagenized, recombinant hormone may be produced in large amounts, with each batch exhibiting uniform biochemical and biological properties. Therefore, this product would be an excellent choice as a reversible contraceptive in men and women.
