THE ADRENAL GLAND 2/5 



above was followed by marked reductions in adrenal ascorbic acid, yet 

 similar treatment of hypophysectomized animals failed to affect the 

 level of the vitamin in the gland. The ascorbic acid content of other tis- 

 sues was not affected either by adrenotrophic hormone or by exposure 

 of animals to conditions that were followed by a decline in its content 

 in the adrenal. 



While it might be argued that these changes in adrenal cholesterol 

 and ascorbic acid are only an indirect measure of adrenal cortical secre- 

 tion, our experience has convinced us that they furnish a reliable and 

 rapid indicator of this secretion. As I have pointed out above, this is ap- 

 parently mediated by the preliminary passage into the blood stream of 

 additional quantities of the pituitary adrenotrophic hormone. Even if 

 these changes in adrenal cholesterol and ascorbic acid were not directly 

 associated with the elaboration and secretion of the cortical hormones 

 but were merely expressions of a general heightening of adrenal metab- 

 olism, they would still be of value for following the secretory activ- 

 ity of the gland. However, there is other evidence that more directly 

 links these changes in adrenal chemistry with the actual formation and 

 release of the cortical steroids. Bloch and Rittenberg have shown by the 

 use of cholesterol tagged with deuterium that not only the bile acids but 

 also progesterone are formed from this steroid. The structure of proges- 

 terone is sufficiently akin to that of the corticosterones to make it ex- 

 tremely probable that the latter also are formed from cholesterol. 



At least one role of ascorbic acid in the adrenal would appear to have 

 been clarified by the recent report of Lowenstein and Zwemer (8) that 

 it is possible to isolate from this gland a water soluble and biologically 

 active steroid in which the steroid nucleus is linked with ascorbic acid. 

 If this is correct then ascorbic acid is actually a part of the hormone in 

 the form it is secreted by the gland, cholesterol presumably furnishing 

 the material from which further quantities of the steroid portion may 

 be elaborated as it is required. 



The association of a vitamin with a hormone in this manner is the 

 first known example of a common point of activity of members of these 

 two important groups of substances, although examples of vitamins 

 forming portions of co-enzymes are now fairly numerous. The recent 

 report of Price, Colowick and Cori (9) on the influence of insulin, an- 

 terior pituitary, and cortical hormones on the activity of the enzyme 

 hexokinase is an outstanding instance of such interplay, particularly 

 since nicotonic acid amide is a component of the hexokinase system. In 



