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 r ecombinant human thyrotropin (rhTSH) have been carried out in the mous e. We have recently reported that 0.1 mg of rhTSH IM (one-ninth the do se given in thyroid cancer patients) given to normal subjects elicits a brisk rise in serum thyroxine (T-4), triiodothyronine (T-3), and thy roglobulin (Tg) concentrations. In contrast, in initial studies in the rat, a low dose of rhTSH failed to increase serum T-4 or T-3 concentr ations. The present study was, therefore, carried out to determine the biological activity of rhTSH in euthyroid and in T-3-treated, TSH-sup pressed rats and mice. Doses of rhTSH based on body weight were used a nd resulted in similar serum human thyrotropin (hTSH) concentrations i n the two species. Euthyroid and TSH-suppressed mice responded briskly to rhTSH administration. In contrast, serum T-4 did not increase afte r rhTSH administration in euthyroid rats. In TSH-suppressed rats, the increase in serum T-4 was similar to that observed in TSH suppressed m ice. These observations suggest that rhTSH more readily displaces endo genous TSH from the mouse than from the rat thyroid TSH receptor, beca use equal responses were observed when endogenous TSH was suppressed.