PHYSIOLOGY, PHARMACOLOGY, AND TOXICOLOGY 383 



marked (fortyfold) hypertrophy induced in the chick oviduct by stil- 

 bestrol does not occur in folic acid-deficient chicks and to only a moderate 

 degree in pantothenic acid-deficient chicks. 20 Thus in experiments in 

 which chicks were maintained on appropriate deficient diets for fifteen 

 to nineteen days following which they received daily subcutaneous in- 

 jections for six days of 0.5 mg of stilbestrol, autopsy revealed folic 

 acid-deficient chicks to have an average oviduct weight of 62 mg; 

 pantothenic-deficient chicks had average oviduct weights of 281 mg, with 

 weights for controls receiving 20 jxg of folic acid daily from birth of 450 

 mg. It has been shown that there is a direct quantitative relationship 

 between the oviduct response to stilbestrol and the dietary level of folic 

 acid. Riboflavin and pyridoxine at least do not behave in a similar man- 

 ner. 30 Later work has indicated strongly that a similar relationship is 

 true in the folic acid-deficient monkey on estradiol treatment, and that 

 it is probably a general phenomenon. 31 It has been suggested 32 that all 

 rapid cell proliferation requires special amounts of folic acid for the 

 necessarily rapid synthesis of nuclear thymine and purine bases. This 

 suggestion is of some particular interest in view of the role of folic acid 

 in erythropoiesis and the observed effects of folic acid analogues on tumor 

 growth. 33 



Reference to this response of the chick oviduct calls for at least passing 

 mention of the fact that it is in the oviduct that biotin-binding avidin 

 is laid down in the hen's egg. 34 An extended discussion of the genesis and 

 significance of this naturally occurring antivitamin is not expedient at 

 this time, although it should be noted that there is as yet no acceptable 

 explanation for the functional occurrence of this substance. Despite earlier 

 hopes, little of significance from the standpoint of an understanding of 

 its fundamental role in metabolism has been discovered. 



A consideration of various aspects of the reproduction process — game- 

 togenesis, mating behavior, the estrus cycle, embryonic development, 

 lactation, and maternal instinct — shows at once that adequate B vitamin 

 nutrition is essential to the process for many reasons that may be con- 

 sidered in terms of general health. 35 Thus, the production of viable sperm 

 and ova, development of the embryo, and the maintenance of satisfactory 

 lactation are linked to B vitamin activity, largely because normally func- 

 tioning cellular and tissue elements are essential to these processes. No 

 specific B vitamin relationship is known to be directly involved beyond 

 this, although special "lactation factors" have been reported in experi- 

 mental work from time to time. 30-39 Indirectly, B vitamin-endocrine 

 relationships may influence these processes as well as mating and maternal 

 behavior. The estrus cycle, and all the phases of reproduction directly 

 influenced by estrogens, are directly concerned with the B vitamins in 



