BIOSYNTHESIS, GLYCOSYLATION, AND ACTION OF THYROTROPIN--CLINICAL TRIALS OF TSH

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Recombinant thyrotropin which is used to stimulate radioiodine uptake in patients with thyroid cancer has been produced by novel methods of transfection of alpha and hTSH beta minigenes into Chinese hamster ovary cells. Utilizing products produced in a large scale bioreactor as well as a hollow fiber bioreactor, we have been able to purify several hundred milligrams of this product. Terminal sialylation of recombinant TSH determines in vitro and in vivo bioactivity as well as clearance rate. The carbohydrate structure of recombinant TSH has been characterized in detail and differs from pituitary TSH. The role of sugar structures in bioactivity has also been clarified by enzymatic deglycosylation. Site-directed mutagenesis as well as production of novel recombinant hybrids has been used to develop new TSH analogs with prolonged half life. We have also developed competitive antagonists of TSH which will be useful in treatment of patients with hyperthyroidism and thyroid cancer.