140 KINETIC HORMONES — II 



was that the thyroid gland of frog tadpoles, Rana, regressed and 

 might atrophy, if the hypophysis was removed. The tadpoles then 

 failed to metamorphose ; but could be induced to do so by injections 

 of a hypophysial extract containing thyrotrophin, TSH. This 

 stimulated renewed growth of the thyroid gland and the formation 

 and release of thyroxine, which in turn induced metamorphosis. 



Mammalia. It seems clear that here (and in birds. Bates and 

 Cornfield, 1957) the discharge of thyroxine from the thyroid into 

 the blood circulation occurs in response to stimulation of the gland 

 by TSH. The action is, however, not altogether simple, since 

 evidence is accumulating for there being either two separable 

 actions of TSH, or possibly two hormones; one stimulating the 

 growth of the thyroid gland, and the other its iodine metabolism 

 and secretion. 



The cycle of iodine metabolism has been worked out in some 

 detail, partly by means of studies on radioactive iodine (P^^), 

 which can be followed through the tissues in vivo (Taurog et al., 

 1958). Iodides, derived from food and from the breakdown of 

 disused thyroxine, circulate in the blood, whence they are trapped 

 by the thyroid gland and oxidized to iodine. (This reaction is 

 specific and much more efficient than that by which other halogens 

 and related elements are picked up by the thyroid.) In the gland, 

 iodine is attached to an organic molecule to form thyroglobulin, 

 which is a precursor of the hormone. It is stored as a characteristic 

 colloid in the intrafollicular lumen (Fig. 4-7 a-c). It can then be 

 hydrolysed by a proteolytic enzyme to release thyroxine into the 

 circulation (Fig. 4-7 d-e). This filters through the capillary walls 

 to reach the tissue spaces, and bathes the cells before being 

 drained into the lymphatics. The thyroxine accumulates in the 

 peripheral tissues and, notably, in skeletal muscle, where it seems 

 to be concerned with the activity of tissue enzymes. When the 

 tissue hormone is broken down through use, it yields up iodides to 

 the circulation, and the cycle starts afresh (Salter, 1949). 



TSH acts upon this cycle in the thyroid gland itself. Its first 

 eff"ect is to activate the enzyme converting the stored thyroglobulin 

 to thyroxine, and its second is to stimulate the release of thyroxine 

 into the circulation. This reaction is rather slow in rats, and may 

 only be detectable histologically after 22 hr (Fig. 4-8). At the same 



