IX. EFFECTS OF DEFICIENCY 197 



pionate. It was also found in confirmation of the work of Hertz'"^ that 

 PGA doficiency was the only one that interfered with the oviduct weight 

 produi'ed by estradiol. Zarrow ct n/."' observed that a P(«A deficiency 

 produced either by feedinji; a purified diet or a commercial chick mash 

 contaiuini»;2 % of crude "x methyl PGA" had no effect on the comb stimu- 

 lation produced by testosterone. Four per cent of this antagonist actually 

 enhanced the eiTect of androgen on comb growth. 



Dehydroisoandrosterone acetate in relatix'ely large amounts has been 

 found b}' Gaines and Totter''^ to stimulate the growth of S. faecalis and 

 L. casei in the absence of PGA. Cortisone acetate has been found to support 

 the growth of Leuconostoc citrovorum in the absence of the citrovorum 

 factor."^ 



13. Role of Citrovorum Factor in Animal Nutrition 



Just as leucovorin (synthetic citrovorum factor) can meet the require- 

 ment of certain microorganisms for PGA, it has also been found that leuco- 

 vorin is active in promoting growth and hemopoieses in PGA-deficient 

 chicks and turkeys. ^'""'-^ Experiments with crystalline leucovorin have 

 shown that, when it is mixed with the ration of chicks or turkeys, it is 

 considerably less active than PGA; but the two substances have similar 

 activities when injected. Experiments with leucovorin in chicks may be 

 compared with numerous studies that have been conducted with leuco- 

 vorin in anemia in which it has been shown that leucovorin, like PGA, is a 

 potent hemopoietic agent in pernicious anemia, sprue, and nutritional 

 macrocytic anemia.'-'' 



The disco\'ery that leucovorin is more active than PGA in reversing the 

 toxicity of 4-amino PGA for S. faecalis is paralleled by experiments with 

 mice in ^^'hi('h the same relationship was found.'-" There are now many 

 instances of the ability of leucovorin to counteract the action of 4-amino 

 PGA or its close chemical derivatives. Thus Burchenal and coworkers'^^ 

 found that leucovorin when administered prior to 4-amino- 10-methyl PGA 

 completely counteracted the antileukemic effect of this antagonist in mice 



'" M. X. Zarrow, I. B. Koretsky, and I. G. Zarrow, Endocrinologij 48, 125 (1951). 



>'8 D. S. Gaines and J. R. Totter, Proc. Soc. Exptl. Biol. Med. 74, 558 (1950). 



•" D. S. Gaines, H. P. Broquist, and W. L. William.s, Proc. Soc. Expll. Biol. Med. 77, 



247 (1951). 

 '=« H. P. Broquist, K. L. R. Stokstad, and T. H. Jukes, ./. Biol. Chem. 185, 399 (1950). 

 '-' H. P. Broquist, J. A. Broekman, Jr., M. J. Fahrenl)ach, 10. L. R. Stokstad, and 



T. H. Jukes, J. Nutrition 47, 93 (1952). 

 '22 E. G. Hill and G. iM. Briggs, Proc. Soc. Exptl. Biol. Med. 76, 417 (1951). 

 '" T. D. Spies, G. G. Lopez, F. Milanes, R. L. Tooa, A. Rehoredo, and R. E. Stone, 



Southern Med. ./. 43, 1076 (1950). 

 '-' J. II. Burchenal, S. V . Johnston, II. V. Bro(|uis(, and T. II. Jukes, Cancer Research 



10, 208 (1950). 



