STRUCTURE/FUNCTIONAL ANALYSIS OF INHIBIN

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DESCRIPTION (Adapted from applicants description): Inhibins and activins are related gonadal protein hormones that, respectively, inhibit or stimulate FSH release by pituitary gonadotrophy. Recent studies suggest that tandem fusion of gonadotropin alpha and beta subunit cDNAs confers efficient secretion of the dimer proteins without affecting their bioactivities. Based on the structural similarity between inhibins and gonadotropins, it is hypothesized that fusion of the inhibin alpha and beta subunit cDNAs might allow efficient expression and secretion of the heterodimer. The preliminary data indicated that earlier difficulties in producing inhibin over activin can be overcome by synthesizing inhibin dimers following fusion of the beta and alpha subunit cDNAs. It is proposed to further characterize the inhibin isoforms produced by this method and to increase the processing of mature inhibins by transfecting cell lines known to contain proteolytic enzymes important for pro-protein processing. The bioactivity of mutant inhibin isoforms and perform structure-functional analysis to elucidate the importance of N-linked carbohydrate side chains. It is anticipated that these studies would lead to a better design of inhibin agonists and antagonists as well as efficient production of recombinant inhibins of clinical use.