158 PHYSIOLOGICAL TRIGGERS 



mechanism of action for certain drugs, may be indicated (cf. 24). Indeed, some 

 striking parallelisms present themselves. 



The absence of well-documented instances of characteristic hormonal action 

 in homogenates is but one facet of the accumulating evidence in support of 

 this concept, although alternative mechanisms are not excluded on this basis 

 alone. Rapid examination of the array of hormones whose action has been 

 studied in some detail reveals further data consistent with the general thesis. 

 In each instance, the rather specific transfer of a key metabolite appears to 

 underlie the subsequent, relatively nonspecific results of hormone action. For 

 example, the recent studies of Levine and Goldstein (20), and of Drury and 

 Wick (9), now widely confirmed (cf. 31), appear to establish as one mode of 

 action of insulin,- its participation in enhancing the permeability of the muscle 

 cell to glucose (and to other carbohydrates of rigidly specific structure), a 

 response which is abolished by freezing and thawing of the tissue (19). 



Similarly, the requirement of cellular integrity (12, 14, 26) for the charac- 

 teristic in vitro action of ACTH in promoting steroid biosynthesis in adrenal 

 preparations, coupled with the unrestrained rates of synthesis in homogenates 

 (21), would appear to suggest (cf, 11) that ACTH may act on its target organ 

 by removing cytostructural barriers to substrate-enzyme interaction. The 

 facilitation by ACTH of the rate of penetration of inorganic P^^ into adreno- 

 cortical cells in vivo (cf. 26), the augmentation of the effect of ACTH on corti- 

 coid biosynthesis in the perfused adrenal by high levels of potassium in the 

 perfusion fluid (43), the requirement of calcium (4) and of glucose (28) for 

 ACTH action on adrenal slices in vitro notwithstanding the failure of calcium 

 (4) or glucose (28) deficiency to affect the rate of steroid biosynthesis in the 

 absence of ACTH, and a number of other considerations (cf. 14), suggest that 

 the postulated role of ACTH in regulation of permeability relationships of the 

 intact target cell is consistent with the data thus far available (cf. 13, 14). 



As is well known, shifts in ionic environment of the cell may influence in a 

 striking manner its metabolic activities. Altered ion permeability of the cell 

 membrane through the influence of a given biocatalytic substance may thus 

 have far-reaching consequences to the metabolic processes within the target 

 cell (cf. 24). This mechanism has been invoked by Szent-Gyorgyi in connection 

 with the mode of action of epinephrine in affecting cardiac muscle tension, 

 secondary to changes in intracellular cationic environment (cf. 12). Hajdu and 

 Szent-Gyorgyi have described antagonistic effects of individual steroids upon 

 heart muscular tension, and have ascribed these effects to counteractive in- 

 fluences upon intracellular ionic environment, achieved through modification 

 of permeability of the cell membrane (cf, 40). Analogous studies conducted 

 by Csapo and colleagues (cf. 8, 15) on estrogen- and progesterone-dominated 

 rabbit uterine muscle give strong support to a similar mechanism. 



One additional example of the potential importance of membrane permeability 

 alterations as a common denominator for ubiquitous actions of the hormones 



