Prolonged Injection of a Thyrotropic Extract Without Development of Refractoriness. ∗

Abstract

It has been uniformly reported that repeated injections of hypophyseal extracts containing the thyrotropic hormone fail to stimulate the thyroid gland beyond 4 or 5 weeks. The BMR and thyroid structure return to normal. This has been explained by Collip 1 as due to the increase of a normally present “antihormone.”This theory has also been applied to the other hypophyseal hormones.

Results obtained in this laboratory with 2 different hypophyseal preparations containing the thyrotropic hormone do not support the “antihormone”hypothesis. The development of refractoriness has been found to depend on the type of extract in which the hormone is administered. The thyrotropic effect has been determined by the BMR, the microscopic structure and total iodine content of the thyroid gland. The author is very grateful to Dr. G. L. Foster of the Department of Biochemistry for his kindness in doing the iodine determinations. The determinations were made by his modification of Leipert's 1934 method.

Male guinea pigs, 250–350 gm. in weight, were used. They were maintained under constant conditions in a room in which no iodine was kept or used. The 2 preparations employed were made from beef anterior hypophyses by the van Dyke and Wallen-Lawrence Na₂SO₄ method 2 and by the flavianic acid method of Meyer.† The BMR was measured after a 13–16 hr. period of fasting in a closed system apparatus maintained at 30°C. ± 0.1°.

A. Treatment with the Na ₂ SO ₄ preparation. Eleven animals were injected daily subcutaneously with one cc. of the Na₂SO₄ preparation for 23–40 days. All of these showed a pronounced increase in the BMR during the first 2 weeks of treatment. Ten of these animals showed a return of the BMR to normal. Three of the refractory animals were autopsied and had structurally normal thyroids.