VII. VITAMIX A DEFICIENCY IX ANIMALS 125 



oi racliilii' inls hd'ori^ and at"t(>r cxccssixc \ilaniiii A a<liirniisl rat ion. 'I'lic 

 liiulinjis result iiiii; from the \ilainiii .\ excess weic a ne<iati\-e iiili-oj^eii hal- 

 ance, an excess of calcium excretion oxer intake, and a prompt maiked 

 negative pliospliorus balance.'" 



A specific inten-elation hetweeii \-itamin .\ and th\roid function has been 

 a fre(iuent conclusion hy clinician.s and a few laboratory workei's. The 

 predominatinii- opinion is that vitamin A is antajionistic to thyroid function. 

 Too frecjuently, preparations containini>: larj^e amounts of vitamin 1) have 

 been employed in the lal)oratory as well as in the clinic. Drill has reviewed 

 the subject up to 1943. •'•' Pul)lications since 1943 have not produced satis- 

 factory evidence of either a dirtM't action of \-itamin A upon thyroid function 

 or an indirect influence through the pituitary gland. Considerable evidence 

 has appeared that there has been too little consideration and/or under- 

 standing of the proved consequence of vitamin A deficiency and of hyper- 

 vitaminosis A. 



2. Skeletal Responses' •'*• ^^ 



As m vitamin A deficiency, the fully grown skeleton is not demonstrably 

 influenced b}^ excessive amounts administered to rats over long periods. In 

 growing animals — rats, gumea pigs, mice, dogs, ducks, and chicks — pro- 

 found changes result which can ):e correlated with the normal species 

 growth patterns of the bones and accurately expressed as accelerations of 

 those processes retarded by the deficienc3^ 



In rats, guinea pigs, dogs, and chicks, '^'^ the changes that have been 

 studied histologically are those of epiphyseal cartilage and those concerning 

 remodeling of bones — the resorption of bone, compact bone formation, and 

 appositional bone formation. Common to all species is rapid maturation 

 of epiphyseal cartilage cells and more rapitl penetration by blood vessels. 

 In guinea pigs the acceleration of endochondral bone formation, if the high 

 vitamin A dosage (1000 to 1250 I.T. per gram) is begun a few days after 

 birth, results in complete consumption of the cartilage in 10 to 15 days, 

 and, as osteoid production keeps pace with the cartilage seciuences, a plate 

 of bone results as in the early stage of epiphyseal closure. This result, 

 obtained in the distal femoral and proximal tibial epiphyses, corresponds 

 to the normal at about 30 to 00 weeks of age, respectively (Fig. 30). Clo- 

 sure of the same epiphysis has not been the result in the rat, but in the 

 normal animal closure of these epiphyses does not take place. Another 

 species difference is that in the rat in experiments of short duration with 

 heavy dosages the width of the epii)h\-seal cartilage ])late may remain 



" C. L. Maddock and S. B. Wolhach. Federation I'mr. 9, 337 (1950). 



"V. A. Drill, Physiol. Revs. 23, 355 (1943). 



36 T. E. Van Metre, Jr., Bull. Johns Hopkins Hosp. 81, 305 (1947). 



