512 VERTEBRATE LIFE AND ORGANIZATION 



completely prevents metamori^hosis and administering thyroxin to tad- 

 poles causes them to metamorphose prematurely into miniature adults 

 (Fig. 30.3). 1 he effect of thyroxin on amphibian metamorphosis ap- 

 pears not to be simply a secondary result ot its effect on metabolism, for 

 tadpole metabolism can be increased by dinitrophenol but premature 

 metamorphosis does not occur. Some specific effect of thyroxin on 

 metamorphosis appears to be involved. 



Thyroxin stimulates the oxidative, energy-releasing processes in 

 all tissues of the body. Our current biochemical concept is that it 

 uncouples the phosphorylation process from oxidative processes so that 

 the latter occur rapidly, yet energy, as energy-rich phosphate bonds 

 (p. 67), is less available. 



The production and discharge of thyroxin is not regulated by the 

 nervous system, but by the hormone thyrotropin secreted by the an- 

 terior lobe of the pituitary gland. In 1916, P. E. Smith found that the 

 removal of the pituitary of frog tadpoles produced deterioration of 

 the thyroid and prevented metamorphosis. The same pituitary control 

 of thyroid function has been found in rats, man and other mammals. 

 The secretion of thyrotropin by the pituitary is regulated in part by the 

 amount of thyroxin in the blood. Thus, a decreased production of 

 thyroxin by the thyroid leads to less thyroxin in the blood stream and 

 this stimulates the pituitary to release thyrotropin, which passes to the 

 thyroid gland and raises its output of thyroxin. When the blood level 

 of thyroxin is brought back to normal, the release of thyrotropin is 

 decreased. By this "feed-back" mechanism the output of thyroxin is 

 kept relatively constant and the basal metabolic rate is kept within the 

 normal range. Since iodine is an essential atom in thyroxin, a deficiency 

 of this element leads to decreased synthesis of thyroxin. Iodine de- 

 ficiency stimulates the thyroid follicle cells to enlarge and to increase 

 in number. The enlargement of the thyroid is known as a goiter. 

 Thiouracil and related compounds are goitrogenic. They inhibit the 

 production of thyroid hormone by blocking the reactions by which 

 iodide is oxidized and fixed onto the tyrosine molecule. The deficiency 

 of thyroid hormone stimulates the pituitary to release more thyro- 

 tropin, which in turn stimulates the thyroid cells to enlarge and pro- 

 duce a goiter. Thiouracil is used clinically to decrease thyroxin pro- 

 duction by hyperactive thyroids. 



The chief human diseases of the thyroid are cretinism, myxedema, 

 simple goiter and exophthalmic goiter. Thyroid deficiency in infancy 

 produces a dwarfed, mentally retarded child known as a cretin (Fig. 

 30.4 A). A cretin has an enlarged tongue, coarse features, malformed 

 bones, distended belly and wrinkled, cold skin. If thyroid therapy is 

 begun early enough, normal development of the brain and body can 

 be induced. Thyroid deficiency in adults results in myxedema, char- 

 acterized by decreased metabolic rate, mental deterioration, obesity, 

 loss of hair and cold rough skin. Simple goiter, or enlarged thyroid, 

 results usually from a deficiency of iodine, with a secondary increase 

 in the size of the thyroid due to its stimulation by thyrotropin (Fig. 



