2. Endocrines and Populations 231 



in the formation of thyroxine than the one given above (Rawson et al., 

 1955). However, the metabohc pathway given is the usually accepted 

 scheme for the synthesis of thyroxine. Thyroxine presumably is released 

 from thyroglobulin by the action of proteolytic enzymes (SoUman, 1957). 

 Thyrotropin promotes the iodination of tyrosine and the release of thyrox- 

 ine from thyroglobulin. A small amount of thyroxine loses one of its 

 iodine atoms to become /-.3,5,o'-triiodothyronine in the thyroid, probably 

 more in the peripheral tissues, and small amounts of this compound are 

 found in the thyroid gland and in circulation (Gross, 1955). /-3,5,3'- 

 Triiodothyronine has a more pronounced action on oxidative processes 

 than thyroxine, and its action is much more rapid, but less prolonged 

 (Sollman, 1957). It has been postulated that the triiodothyronine provides 

 the immediate thyroid response and is the substance which enters the cells 

 and exerts the ultimate thyroid action, whereas thyroxine is the circulating 

 form of the thyroid hormone (Gross, 1955). The differential distribution 

 of these two hormones in the circulation and in the cells of various tissues 

 supports this hypothesis (Gross, 1955). Since inorganic iodide is essential 

 for the normal functioning of the thyroid gland, the rate at which radio- 

 active iodine is trapped and accumulated by the gland is a good index of 

 thyroidal activity provided there is not an increased renal excretion of 

 iodine. The rate of release of radioactive iodine from the thyroid is con- 

 sidered a more reliable and reproducible index of thyroid activity, as each 

 animal can serve as its own control in experimental procedures (Brown- 

 Grant et al., 1954a). 



3. Factors That Regulate the Activity of the Thyroid 



The secretory activity and hormone synthesis by the thyroid is largely 

 under the control of the protein hormone thyrotropin (TSH) secreted by 

 the basophils of the anterior pituitary (D'Angelo, 1955). However, the 

 thyroid is capable of a low level of autonomous function without stimulation 

 by the pituitary (Brown-Grant et al., 1954a). The rate of release of TSH 

 from the anterior pituitary is apparently related to the level of circulating 

 thyroid hormone (D'Angelo, 1955), although the mediation of the hypo- 

 thalamus appears to be required (Harris and Woods, 1958; D'Angelo and 

 Traum, 1958) ; therefore a low level of circulating thyroid hormone stimu- 

 lates an increased secretion of TSH and a high level inhibits its secretion. 

 This is the classic concept of an endocrine feedback mechanism which 

 operates to regulate the release of hormone from the target gland and to 

 maintain a more or less constant level of circulating hormone under normal 

 circumstances. However, there is recent evidence to suggest that the secre- 

 tion of TSH may not be a direct response to the level of circulating thyrox- 



