ACTIVATION OF THE PROVITAMIXS D 657 



According to the most recent data summarized in Table 5, as much as 

 4% of the total \dtamin D and its breakdown products are present in the 

 bones. It is the opinion of Kodicek-^^ that vitamin D is concentrated in 

 the sites where the turnover of inorganic phosphorus is taking place, such 

 as the Uver, bones, and intestinal wall. 



The further fate of vitamin D is not knoMii. It is possible that it 

 remains in the several tissues for a period of time, and is gradually destroyed 

 in situ as it carries out its physiologic function, or that it is gradually ex- 

 creted via the bile Tvithout decomposition in the tissues. It has already 

 been recorded that a certain amount of vitamin D can be reexcreted into 

 the intestine through the bile,^!^. 216,222-225 ^g ^-^\i ^g j^,^-^^ ^^g walls of the 

 upper one-third of the small intestine.--® Heymann-^^'--^ observed that a 

 slow reexcretion of \'itamin D in the bile of dogs continued for months 

 after the administration of the vitamin had been discontinued. Coppens 

 and Metz^^^ reported that an enzyme occurs in the lungs which destroys 

 vitamin D. In the case of pregnant females, there is also the possibility' 

 that some \dtamin D would be transferred to the fetuses. Thus, Embleton 

 and Collings-^^ have reported that young rats receive supplies of \atamin 

 D from the doe either via the placenta or from the milk during lactation. 



4. The in vivo Activation of the Provitamins D 



The activation of the several pro\-itamins D in the test tube is well 

 understood from both the physical and the chemical \dewpoints, and has 

 been discussed in an earher section of this chapter (see pages 639 to 641). 

 Until 1943 there had been less information concerning the in vivo trans- 

 formation of the provitamins D to their corresponding \dtamins D. In 

 this year, Geiger and Lassen^^ found that the subcutaneous or oral ad- 

 ministration of 7-dehydrocholesterol which had been activated by arc 

 lamp irradiation had a pronounced curative effect upon rachitic rats. The 

 subcutaneous injection of the provitamin D into the depleted rats was 

 effective only if the rats were irradiated daily. However, irradiation alone 

 was ineffective. In later studies these workers-^^^ demonstrated that 7- 

 hydroxycholesterol and 7-ketocholesterol, injected subcutaneously into 

 rats subsequently exposed to ultraviolet irradiation, had a greater anti- 

 rachitic potency than did 7-dehydrocholesterol administered under similar 

 conditions. Administration of these provitamins D per os was less effec- 

 tive than was the subcutaneous method, indicating faulty resorption of 



2^E. Kodicek, Personal communication to the author, October 10, 1955. 



"9 J. Embleton and A. J. ColUngs, Nature, 159, 340-341 (1947). 



"9» S. Lassen and E. Geiger, Proc. Soc. Exptl. Biol. Med., 53, 181-183 (1943). 



