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Endocrinology, Vol 120, 567-573, Copyright © 1987 by Endocrine Society

ARTICLES

Monoclonal antibodies can enhance the biological activity of thyrotropin

AT Holder, R Aston, JR Rest, DJ Hill, N Patel and J Ivanyi

In this work we demonstrate that monoclonal antibodies (MABs) to TSH can enhance the biological actions of TSH in vivo. Hypopituitary Snell dwarf mice were injected with TSH (25, 50, or 100 mU/day) alone or complexed with MAB-GC73 once per day for 5 days; control animals received PBS. Radioactive sulfate (35SO4(2-)) was also injected on the fifth day and animals were killed 20 h later. Thyroids were removed for histology, blood taken for T4 estimations by RIA, and 35SO4(2-) uptake into costal cartilage in vivo was measured. In control mice thyroid histology revealed small follicles comprised of small flattened epithelial cells with a high nuclear-cytoplasmic ratio; colloid was dark with little vacuolation. In animals treated with TSH alone there was moderate evidence of activation in most of these features. However, a marked response was noted in animals treated with TSH plus MAB-GC73; characteristically, there was little interfollicular tissue and the follicles, which were large and comprised of cuboidal cells, contained pale, finely vacuolated cytoplasm. Both TSH alone and TSH complexed with MAB-GC73 promoted a significant dose-dependent increase in serum T4 levels. The two higher doses of TSH plus MAB-GC73 promoted a significantly greater increase in serum levels of T4 than that in groups receiving the same dose of TSH alone. Uptake of 35SO4(2-) into costal cartilage showed a significant correlation with serum T4 levels. In similar experiments significant increases in salivary gland epidermal growth factor content of male dwarf mice were observed. This work demonstrated that MAB enhancement of hormone action is not restricted to human GH, suggesting a more general phenomenon.


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