Metabolism in Normal and Thyroidectomized Rats as Influenced by Thyroxine and Thyroid Globulin Feeding

Abstract

The evaluation of thyroid preparations is still in an inchoate state, because (1) the accepted method, based on iodine content, does not give an estimation of the physiologic activity, since the thyroxine component of standard products may vary considerably (up to 600% as found by Harrington and Randall 1 ); (2) the methods of thyroxine assay available give more comparative than absolute values; (3) the physiologic action of thyroid substance or extract seems to depend partly on the chemical linkage between the thyroxine and other groups present. While the investigation of Thompson and co-workers 2 showed that the potency of thyroid substance is considerably reduced by hydrolysis, which would break up such linkages, Palmer et al. 3 concluded from their experiments on guinea pigs that the calorigenic action of thyroid substance is a direct function of the thyroxine contained, which, however, is present in the l-form and twice as potent as the commonly prepared racemic mixture.

In our attempt to find a reliable and fairly accurate method of bioassay, we used first normal and later thyroidectomized male rats, finding in the latter a far more suitable test animal. In this we are at variance with the work of Gaddum, 4 which is probably explainable by the difference in the age of the rats used.

A closed circuit apparatus was used, as described by Benedict. 5 The normal rats used were 80-100 days of age. Thyroidectomy was performed when the rats were 70-90 clays old. In the latter case, at least 3 weeks were allowed for recovery. The rats were starved for 20 hours and allowed to remain for 30 minutes in the respiration chamber before testing. The temperature was kept constant at 30° throughout the experiments. The time necessary for the consumption of a constant volume of oxygen was measured, and results calculated as mg O₂ per hour per kg weight.