HORMONES 



the hormones by extraglandular tissue. How do these patterns 

 become fixed? 



There is at present no vahd answer to this question. One 

 reason why an answer evades us is our inabiHty to assess in even 

 approximate quantitative fashion the degree of interdependence 

 of the various hormonogenic systems of the body. From 

 laboriously attained bits and pieces of evidence we have the 

 beginnings of an understanding of such interdependencies. We 

 know, for example, that adequate estrogen action requires 

 adequate thyroid hormone, that the secretion of ACTH may be 

 suppressed by various corticosteroids, that pituitary gonado- 

 trophin release depends in the rat on an estrogen-progestin 

 balance. Is there a key pacemaker to this system of checks and 

 balances? Or are we dealing with a complex servel mech- 

 anism? Are there endogenous antihormones which play a role 

 in the complex hormone equilibrium? Certainly in any con- 

 sideration of the effectiveness of hormone secretion it is important 

 to evaluate those influences which tend to inactivate the hor- 

 mones. For every known hormone there exists in vivo one or 

 more inactivating mechanisms. These are enzymatic systems 

 which oxidize, reduce, detoxify. What is their quantitative and 

 qualitative contribution to the endogenous hormone pattern? 

 What regulates their rate of functioning? We have recently ex- 

 amined a blood-borne enzyme system that inactivates ACTH. 

 Its concentration in the blood of certain individuals is negligible, 

 whereas in the blood of others it is so high as to effect ex- 

 tremely rapid loss of ACTH activity. What is the biochemical 

 basis of this large individual difference? 



We have indicated that both the rate of secretion and the 

 rate of destruction are key processes in the setting of hormone 

 balance. One other functional phenomenon still scarcely ex- 

 plored requires mention — the phenomenon of action of the end 

 organ. One characteristic of the biological response of or- 

 ganisms to hormones is variability. Certain individuals show 

 very low response thresholds, others very high ones, and there is 

 a characteristic distribution in between, exemplified by the 



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