298 • HORMONES 



Table 11-1 



Estrogenic potency of various substances 



Effective dose for rats 



Substance Injected (jig.) Oral {\ig.) 



Natural estrogenic hormones 



Estradiol 0.08-0.13 50 



Estrone 0.7-0.8 50-60 



Estriol 10 10 



Synthetic products 



Stilbestrol 0.3-0.4 0.7-1.0 



Hexestrol 0.2 



Doisynolic acid 0.8-0.9 



I I NH2 I NH2 



/ \_0-/ \_CR„— C— COOH ho/ \ 



HO— ( / ^ \ V-CH,-C— COOH HOC V-CHj-C— COOH 



l"" l"" H l"" H 



L-Thyroxine L-Diiodotyrosine 



Thyroxine contains no less than 65.4 per cent of iodine by weight. 

 It was obtained from thyroid glands only after drastic alkaline hydrolysis, 

 which, incidentally, converted the natural L-form into the corresponding 

 DL-mixture. Thyroxine and diiodotyrosine are not present in the living 

 gland in the free state but are contained in a protein, thyroglobulin. 

 This substance has a high molecular weight, estimated at 700,000, and 

 is consequently nondiffusible. It contains a rather constant total amount 

 of tyrosine, diiodotyrosine, and thyroxine residues amounting to 3-4 

 per cent, but the relative proportions of the three vary with the iodine 

 intake. Iodine ingested with food is quickly absorbed by the thyroid 

 and is used to convert more of the tyrosine of thyroglobulin into diiodo- 

 tyrosine and thyroxine residues. Thus the gland acts both as a factory 

 and storehouse for bound thyroid hormone. 



When the hormone is needed in other parts of the body, some of the 

 thyroglobulin is broken down by proteolytic enzymes so that either 

 free thyroxine or small, water-soluble, diffusible peptides containing 

 thyroxine as one of the component amino acids are liberated and carried 

 away by the blood stream. While circulating in the blood the thyroxine 

 is bound rather loosely to one of the plasma proteins. Just what happens 

 when these substances reach the tissues ultimately affected is not known, 

 but free thyroxine apparently is not involved. Nevertheless, pure 

 L-thyroxine, either natural or synthetic, does produce the effects of whole 

 thyroid when administered to animals or to human patients. The term 

 "thyroid hormone" applies to any substance capable of causing the char- 

 acteristic physiological effects and thus includes both free thyroxine and 

 the various bound forms of it existing in the animal body. Diiodotyrosine 

 has no appreciable thyroid hormone activity. 



The mechanism of thyroid hormone synthesis in the body is not known 



