The effect of recombinant human thyrotropin (rhTSH) on thyroid function in mice and rats

The vast majority of studies to determine the biological activity of recombinant human thyrotropin (rhTSH) have been carried out in the mouse. We have recently reported that 0.1 mg of rhTSH IM (one-ninth the dose given in thyroid cancer patients) given to normal subjects elicits a brisk rise in serum thyroxine (T4), triiodothyronine (T3), and thyroglobulin (Tg) concentrations. In contrast, in initial studies in the rat, a low dose of rhTSH failed to increase serum T4 or T3 concentrations. The present study was, therefore, carried out to determine the biological activity of rhTSH in euthyroid and in T3-treated, TSH-suppressed rats and mice. Doses of rhTSH based on body weight were used and resulted in similar serum human thyrotropin (hTSH) concentrations in the two species. Euthyroid and TSH-suppressed mice responded briskly to rhTSH administration. In contrast, serum T4 did not increase after rhTSH administration in euthyroid rats. In TSH-suppressed rats, the increase in serum T4 was similar to that observed in TSH suppressed mice. These observations suggest that rhTSH more readily displaces endogenous TSH from the mouse than from the rat thyroid TSH receptor, because equal responses were observed when endogenous TSH was suppressed.