THE ENDOCRINE CONTROL OF AMPHIBIAN METAMORPHOSIS
Authors: ALLEN BENNET M. 
Published: January 2008

1. The removal of the thyroid gland prevents metamorphosis in amphibians.

2. Elemental iodine administered in sufficient amount to normal, thyroidectomized, or hypophysectomized tadpoles and to those from which both of these glands have been removed brings about metamorphosis.

3. Iodine has greater potency when combined in di‐iodotyrosine than in its elemental form or in inorganic salts. In thyroxin it is much more potent still and there is some evidence to show that it is still more potent in thyroglobulin of which thyroxin appears to be the essential constituent.

4. It seems quite clear that none of the metamorphosing amphibians that have been studied experimentally complete metamorphosis without the influence of iodine and that the thyroid gland, under the control of the hypophysis, is responsible for enabling the tadpole to utilize the minute quantities of iodine normally present in the environment.

5. While the thyroid hormone with its essential iodine constituent is responsible for the control of metabolism and also for metamorphosis, other substances that stimulate metabolism have no capacity for inducing amphibian metamorphosis. This has been demonstrated by experiments with dinitrophenol. On the other hand acetylated thyroxin has lost its influence on metabolism but has retained its full capacity to stimulate amphibian metamorphosis.

6. Different tissues show various degrees of capacity to absorb and retain iodine. Muscle tissue has an especially high capacity for retaining iodine. In the blood, iodine is held in the plasma rather than in the corpuscles.

7. Amphibian larvae show no response to iodine or thyroid stimulation during their early stages of development, acquiring an ability to respond only after they have reached a specific fairly advanced stage of development, differing fairly widely in different species. While axolotls show relatively low responsiveness to the thyroid stimulus, Necturus has not been definitely shown to respond at all.

8. There is an orderly succession of steps in metamorphosis due to differences in the threshold of response in different tissues.

9. In cases of regeneration, the younger tissues respond less actively to thyroid stimulus than do the older tissues.

10. Certain features such as the perforation of the skin by the forelimbs are not under the direct control of the thyroid hormone, while other features such as the resorption of the tail do appear to respond directly to it.

11. The anterior lobe of the hypophysis plays an essential role in the activity of the thyroid gland, which will not function in its absence. The anterior lobe of the hypophysis is not able to induce metamorphosis in the absence of the thyroid gland, but induces metamorphosis only through its influence upon the thyroid gland.

12. The anterior lobe of the hypophysis not only plays an essential role in enabling the thyroid gland to manufacture its hormone but an equally important part in causing the thyroid gland to discharge the accumulated hormone into the blood. This has been shown by both transplantation and by the use of extracts produced in various ways. There is good evidence that the thyroid activity that leads to metamorphosis begins only when the hypophysis becomes sufficiently mature to stimulate it to activity.