GREGORY PINCUS 



gests that liver glycogen deposition results from glucose pro- 

 duced from certain tissue protein catabolized under the in- 

 fluence of Cortisol (13). An examination of the mechanism of 

 Cortisol action must therefore involve not liver glycogenesis but 

 gluconeogenesis from protein. Since the disentanglement of 

 indirect effects has been in itself a task of major proportions, it is 

 perhaps not surprising that studies of the mechanism of Cortisol 

 effects have lagged. The fact is that we do not have an ex- 

 planation of how Cortisol exerts its direct specific effects, nor in- 

 deed do we have this for any of the hormones. 



A number of possible hypotheses have been advanced to 

 explain the mode of Cortisol action. It is interesting that these 

 hypotheses might apply to the discussion of any hormone action. 

 They may be summarized as follows: (7) Cortisol acts as a co- 

 factor to an enzyme system controlling the rate of a specific 

 process ; (2) Cortisol acts to affect the permeability of the cell to 

 substances necessary for certain enzymatic processes; (3) 

 Cortisol acts upon the processes controlling the movement of 

 electrolytes in such a way that the significant concentrations of 

 these electrolytes, both intra- and extracellular, are the rate- 

 controlling factors (9). Thus far every attempt to demonstrate 

 that Cortisol is a component of an identifiable enzyme system 

 has failed. A meaningful characterization of the cellular per- 

 meability alterations that may be ascribed to Cortisol has not 

 been made. Although certain aspects of the general metab- 

 olism of K and Na as influenced by Cortisol have been well de- 

 scribed, the specific effects of their alterations upon cortisol- 

 labile metabolic systems have not been established. If we 

 find ourselves with no explanation of the mechanism of Cortisol 

 action, it is not completely because we lack biochemical re- 

 actions in which Cortisol must play a fairly direct role. Gluco- 

 neogenesis from protein, the effect on muscle-work, the in- 

 teresting cooperative role played by Cortisol with nor-adrenalin 

 in the maintenance of vasomotion in the capillary bed, its func- 

 tion as an antihyaluronidase, its actions on connective tissue 

 elements and the release of effector substances in inflammatory 



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