HORMONES 



in the best instances the answers to questions (2), (3), (4), and 

 (5) are either incomplete or lacking. Let us consider an out- 

 standing example. 



Cortisol as a Hormone Prototype 



Cortisol is firmly established as an adrenocortical hormone. 

 Because of its medical utility, Cortisol, and, interchangeably, its 

 transformation product cortisone, have been during the past 

 five years objects of extraordinarily intensive investigation. 

 How does it originate? The best information available suggests 

 that its biosynthesis as a specific adrenocortical product is ac- 

 complished by at least two major biogenetic pathways (7,10). 

 These are depicted in Figure 1. Adrenocortical enzyme sys- 

 tems responsible for steps (</), (^), (/), and {g) have been de- 

 scribed and partially characterized. The transformations in- 

 volved in (a), the nature of X, and the events occurring in {h) 

 and iji) are unknown. The scission of the side chain of choles- 

 terol to yield A^-pregnenolone (reaction (c)) is known to be 

 expedited by adrenocorticotrophic hormone (ACTH), but (A) is 

 apparently AGTH-independent. It is not certain that these 

 two biosynthetic pathways (one via cholesterol, the other choles- 

 terol-independent) are the only ones occurring in the adrenal 

 cortex. 



When we ask ourselves what does Cortisol do we are con- 

 fronted with a plethora of data. As in the case of the estrogens 

 a great diversity of physiological effects are known. Cortisol 

 is not only glycogenetic, antiphlogistic, protein catabolic, it is 

 also eosinopenic, lymphopenic, an inhibitor of estrogen action 

 on the uterus, edematogenic, glycosuric, hypertensive, aborti- 

 facient, an adjuvant in fat mobilization, a maintainer of vas- 

 cular tone and vasomotion in the capillary bed, antianaphylac- 

 tic, diabetogenic, muscle-work sustaining. It is not possible to 

 ascribe these diverse effects of Cortisol to a single basic action, 

 e.g., its neoglycogenetic activity. Nor can we as yet define a 

 circumscribed set of actions as fundamental, although there have 



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