l62 PHYSIOLOGICAL TRIGGERS 



SUMMARY AND CONCLUSIONS 



The principles illustrated by this rapid analysis of our admittedly meager 

 knowledge of hormonal action on the target cell may be restated briefly: 



It is apparent that while a host of biochemical reactions are influenced (cf. 

 24, 36) during the complex processes of growth and diff'erentiation which con- 

 stitute the over-all response of the uterus to estrogenic stimulation, the primary 

 loci of hormonal action in the target organ are few. Similarly, from available 

 data on non-steroidal hormones, it is likely that direct and indirect responses 

 are distinguishable. 



The manner in which the hormone registers its influence in triggering, at 

 least quantitatively, the chain of metabolic events in the target organ, appears 

 related to the formation of essential links with protoplasmic receptors of a 

 protein nature. These combinations may occur at the cell surface, and lead to 

 modification of the semipermeability of the cell membrane, leading in turn to 

 indirect alterations in enzymatic activity as a result of shifts in ionic constitu- 

 ents and other diffusible regulating substances or substrates. Hormonal alter- 

 ation of the highly specific semipermeability of the cell membrane could be 

 accomplished not only by orientation of the active molecules on the cell surface, 

 but also by interaction with the metabolic systems responsible for maintaining 

 the state of the cell membrane. Evidence is available for the affinity of the 

 steroid hormones for active sites on protein molecules with potential biocata- 

 lytic functions. These observations have not been stressed in the present dis- 

 cussion because of the pharmacological dosage requirements, and because of 

 difficulties in reconciling conflicting in vivo and in vitro data which are frequently 

 diametrically opposed (cf. 24). 



The demonstration of antagonistic interactions among the steroids may 

 furnish clues to the specific loci of their combination with protoplasmic recep- 

 tors (cf. 38, 39), and thus, ultimately, permit analysis of primary vs. secondary 

 effects. 



The gross and metabolic evidences of growth stimulation in response to the 

 appropriate sex steroid, and growth depression as a result of steroid antagonism, 

 are secondary to parallel variations in permeability and carbohydrate metab- 

 olism of the reproductive target organ. At the present stage of development 

 of these problems, it is impossible to distinguish these interrelated phenomena 

 in point of time. A more complete understanding of the mode of action and 

 interaction of the steroid hormones must await elucidation of the precise re- 

 lationship between selective permeability and metabolic phenomena in the 

 cell. It is not unlikely that such information may have wide-spread applica- 

 bility to the general phenomenon of biocatalytic regulation. 



REFERENCES 



1. AsTWOOD, E. B. Endocrinology 23: 25, 1938. 



2. AuDUS, L. J. Biol. Rev. Cambridge Phil. Sac. 24: 51, 1949. 



