HORMONES 



reactions — all these offer the investigator opportunities for 

 analytic dissection. Sooner or later by the study of these or other 

 reactions a definite role for Cortisol will be assigned. That 

 none has been found as yet is perhaps not too surprising. Out- 

 standing metabolic effects of insulin have been known for over 

 thirty years, but the means whereby these effects are exerted are 

 still not definitively established ; similarly, no biochemical mech- 

 anisms have been elucidated for the long-known actions of 

 epinephrine, thyroxin, estrogens, and androgens. 



Our final question concerning Cortisol— what is its fate? — 

 may be partially answered. Its metabolism has been studied in 

 men and animals, in vivo and in vitro. Certain chemical trans- 

 formations which it undergoes have been determined, and the 

 enzyme systems responsible for these transformations have been 

 at least partially characterized (4). The chief known pathways 

 of Cortisol catabolism are presented in Figure 2. The reactions 

 indicated are based principally upon studies of urinary products 

 obtained after the administration of Cortisol, but these data are 

 also in accord with in vitro studies involving Cortisol incubation 

 with liver slices or homogenates. Quantitatively major trans- 

 formations are indicated by heavy arrows, minor ones by the 

 lighter arrows. Compounds II to XIV are products charac- 

 teristic of Cortisol metabolism in human subjects, compounds 

 XV to XVI appear in guinea pig urine following Cortisol ad- 

 ministration (1) and have not been seen in the urines of other 

 species, whereas II to XIV, if they exist in guinea pig urine, 

 have not yet been identified therein. Actually in man the 11- 

 oxygenated 17-ketosteroids (compounds VI, VIII, XI, and XIV) 

 represent 2% to 3% of administered Cortisol and compounds V 

 and VI are the major urinary transformation products, ac- 

 counting for approximately 30%. In man, therefore, some 

 two-thirds of administered Cortisol is unaccounted for in terms of 

 identifiable metabolites. In the guinea pig compounds XV to 

 XVII account for approximately 4% of administered Cortisol, 

 with the probability that a larger percentage may be repre- 

 sented by compounds similar to V to VIII, although it should be 



185 



