652 PANTOTHENIC ACID 



impairment of pituitary-adrenal function in deficient animals as judged 

 by resistance to egg white intoxication or as judged by the extent of ad- 

 renal ascorbic acid depletion and peripheral lymphocyte response follow- 

 ing epinephrine or ACTH administration. 



Morgan and associates'^ have also investigated adrenal function in 

 their animals and have concluded that pantothenic acid deficiency im- 

 poses a stress on the adrenal cortex, resulting in exhaustion of the gland and 

 adrenal hypofunction. Dumm et alr'^ have presented evidence that the de- 

 ficient rat's ability to resynthesize adrenal cholesterol, after stress, is de- 

 creased. 



Cowgill and associates'' and Winters A al?^ have made a further study 

 of the physiological events leading to and accompanying adrenal damage. 

 Using weanling rats which had suckled mothers receiving a pantothenic 

 acid-deficient diet, they were able to secure striking alterations of the adre- 

 nals. Large doses of ACTH (4 mg. per rat per day) produced a marked in- 

 tensification of the adrenal lesion, while cortisone at a level of 2 mg. per 

 rat per day protected the rats completely from cortical necrosis and hemor- 

 rhage. The adrenals in the latter animals (cortisone-treated and pantothenic 

 acid-deficient) were indistinguishable from control animals given cortisone. 

 These investigators concluded that a depletion of coenzyme A in the adrenal 

 cortex leads to increased secretion of ACTH and consequent adrenal hyper- 

 trophy; that the adrenal becomes increasingly unable to produce and 

 secrete steroid hormone; and that the sustained high level of circulating 

 ACTH acting upon the enfeebled gland leads, directly or indirectly, to 

 "hemorrhagic necrosis" of the adrenal cortex. 



It is interesting that, although all observers are agreed that in panto- 

 thenic acid deficiency there is a depletion of adrenal cholesterol and other 

 steroids, it has been reported by Guggenheim and Olson^'" that lipogenesis 

 yer se does not appear to be altered. In their experiments cholesterol con- 

 centrations of the liver, heart and blood serum in deficient animals were 

 normal and C'^ incorporation into cholesterol was not significantly re- 

 duced. 



13 L. S. Hurley and A. F. Morgan, /. Biol. Chem. 195, 583 (1952) ; R. R. Guehring, L. 

 S. Hurley, and A. F. Morgan, ibid. 197, 485 (1952) ; A. F. Morgan and E. M. Lewis, 

 J. Biol. Chem. 200, 839 (1953). 



20 M. E. Dumm, H. Gershberg, E. M. Beck, and E. P. Ralli, Proc. Soc. Exptl. Biol. 

 Med. 82, 659 (1953). 



21 R. W. Winters, R. B. Schultz, and W. A. Krehl, Proc. Soc. Exptl. Biol. Med. 79, 

 695 (1952); R. W. Winters, R. B. Schultz, and W. A. Krehl, Endocrinology 50, 377 

 (1952); R. W. Winters, R. B. Schultz, and W. A. Krehl, ibid. 50, 388 (1952); R. B. 

 Schultz, R. W. Winters, and W. A. Krehl, ibid. 51, 336 (1952). 



2i« K. Guggenheim and R. E. Olson, J. Nutrition 48, 345 (1952). 



