382 THE BIOCHEMISTRY OF B VITAMINS 



is unclear, but testosterone simultaneously produces a marked rise in renal 

 arginase and e?-amino acid oxidase, so that it is felt that the kidney is in 

 some manner involved in these overall retention effects. It has previously 

 been pointed out that the role of the B vitamins is closely associated with 

 nitrogen metabolism in a variety of ways including absorption, storage, 

 and metabolic function. It is therefore apparent that the B vitamins must 

 be considered from a number of standpoints in interpreting the overall 

 metabolic effects of the androgens. 14 



Considerably more concise is the relationship between the B vitamins 

 and estrogen inactivation. 15 - 19 A great variety of ingenious experimental 

 work has shown that the liver inactivates estrogen and androgens both 

 in vivo and in vitro. In the case of estrogens, but not androgens, this 

 inactivation does not occur when the experimental animals are on thi- 

 amine or riboflavin deficient diets, and it has been suggested that the 

 liver inactivation normally involves oxidative steps which are impaired 

 in deficiency. Indeed, it seems well established that cozymase is critical 

 in this conversion. 20 ' 21 Chick liver converts testosterone to 17-keto- 

 steroids, while rat liver carries the process beyond this, further metab- 

 olizing the latter substances. 22 It has been pointed out moreover, that 

 the differences in action on estrogens and androgens during deficiency 

 works to produce a severe imbalance, and working more or less from this 

 viewpoint, Biskind et al. 23 have reported the successful use of B vitamin 

 therapy in the treatment of cases of menorrhagia, metrorrhagia, cystic 

 mastitis, and premenstrual tension. Administration of large doses of 

 thiamine or riboflavin rapidly restores the ability of livers in deficient 

 animals to detoxify estrone or alpha-estradiol, but the restoration of 

 diethylstilbestrol inactivation is less rapid. 24 There is no apparent rela- 

 tionship between liver damage and function in this regard. Inanition and 

 malnutrition, particularly protein deficiency, in general exert a similar 

 effect, and it has been claimed that the effects of thiamine and riboflavin 

 in this regard are not specific, the effect being due to the inanition pro- 

 duced. 25 While this may be true, it seems clear that livers from animals 

 made deficient in pyridoxine, pantothenic acid, biotin and vitamin A do 

 not lose their inactivating ability. 26 It has been suggested, moreover, that 

 the pronounced gynecomastia seen in many male prisoners-of-war in the 

 Orient during the last war may have been due to this effect brought about 

 by the accompanying malnutrition — quite frequently accompanied by 

 ariboflavinosis and mild beriberi. 27 Excess estrogen, moreover, is known 

 to cause adrenal hypertrophy, and it seems likely that the adrenal hyper- 

 trophy associated with certain avitaminoses in rats may be a result of 

 this same impaired liver function. 28 



A second relationship of considerable interest involves the fact that the 



