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Twelve rabbits which had previously generated serum thyroid-stimulating activity in response to 2–3 courses of immunization with human thyroid microsomes were reimmunized, while 6 received injections of thyroxine (T4), 166 μg 3 times a week, and 6 saline. Thyroid- stimulating activity, estimated by the McKenzie assay, rose significantly in the serum of both groups after the experimental course of immunization, although the rise in the T4- treated group was less than that in the control group. The T4-treated rabbits exhibited marked suppression of 131I uptake, enormously elevated serum total and free T4 concentration and significant weight loss, indicating that the thyroidstimulating substance in serum was produced despite supranormal serum levels of thyroid hormone. The serum of 3 of the saline-treated rabbits had a supranormal free T4 concentration in the final post-immunization sample. It is concluded from this and prior studies that the thyroid- stimulating activity of immunized rabbit serum is in large part a globulin of extrahypophyseal origin and is not TSH bound to a globulin. A smaller portion of the thyroid-stimulating activity may be TSH. Finally, the elevated serum free T4 concentration in 3 repeatedly immunized non-T4-treated rabbits suggests that hyperthyroidism may possibly be produced by this technique. (Endocrinology86: 191, 1970)
Solomon et al. (Sun,) studied this question.