Antibody Nature of Refractoriness to Injections of Hypophyseal Extracts Containing Thyrotropic Hormone. ∗

Abstract

It has been shown in the preceding paper that the development of refractoriness to repeated injections of thyrotropic hormone is influenced by the type of extract in which the hormone is contained. This suggests that refractoriness is an immune response to foreign proteins and is not due to the formation of an “antihormone.”If this is the explanation, preparations not inducing refractoriness would be less antigenic. This decrease in antigenicity has been tested and confirmed. No gland iodine determinations were done in this series. The extracts and methods used were the same as in the preceding paper.

A. Effect of non-stimulating doses of the Na ₂ SO ₄ and the flavianate preparations of beef anterior hypophyses on the development of refractoriness in the thyroid. Two series of 6 male guinea pigs each, weighing 250–350 gm., were used. Five of the first series were given 0.1 cc. of the Na₂SO₄ preparation subcutaneously every other day for 32 days. They showed no rise in the BMR. Twenty times this amount (2 cc.) then given daily for 5 days caused no activation of the thyroid, as revealed by the BMR and biopsy specimens of thyroid. The previously untreated control showed a marked response to this large dosage. The second series was treated like the above except that the flavianate extract was used and the treatment lasted for 41 days (0.02 gm. dried gland equivalent was given at each injection). No elevation of BMR took place during this treatment. Twenty times the initial dosage (0.4 gm. dried gland equivalent) was then injected daily for 4 days. It caused marked thyroid stimulation in 3 of the 5 treated animals as well as in the control. The other 2 animals showed only slight thyroid stimulation.