GREGORY PINCUS 



tissue in the mammalian body which is exempt from some sort of 

 hormonal influence either in the course of its development or in 

 its functional activities. Investigations of hormone physiology 

 have quite properly been centered on the more specific actions of 

 these substances, but it becomes more and more evident that the 

 spheres of action are often extremely broad, and frequently far 

 beyond the narrow limits suggested by the tissue of origin and 

 its known interrelationships with other organs and tissues. 

 Thus the expected action of ovarian estrogen as a promoter of 

 female reproductive tract growth and of estrous behavior is ac- 

 companied by multitudinous activities quite outside the repro- 

 ductive realm; estrogens are also hair and bone growth reg- 

 ulators, thymolytic, euphoria-inducing in the menopause, 

 mitogenetic in the epidermis, enzyme inhibitory in the adrenal 

 cortex, phagocyte-stimulating, alkalosis-inducing, antiathero- 

 genic, tumorigenic, antigoitrogenic, antihyperglycemic, en- 

 hancers of cortisone-induced weight loss and glycosuria, hypho- 

 thalamic threshold lowering, anemia-inducing in dogs, etc., 

 etc. Similar multiplicities of action may be cited for most 

 hormones. Out of this welter of activities there arises the con- 

 cept of an array of hormonal substances circulating to the 

 various tissues of the body and interacting in a vast complex of 

 functional processes. 



It is not necessary to labor the point that the hormones are 

 chemically a heterogeneous lot and biologically ubiquitously 

 active. The only thing that unites them is a definition of them 

 as internal secretions. How then may one consider them as 

 biochemical entities? I suggest that for any and every single 

 hormone there are five fundamental questions to be answered: 

 (7) What is its chemical structure? (2) How does it origi- 

 nate? (3) What does it do? (4) How does it do it? (5) 

 What is its fate? In the case of no single hormone do we have a 

 complete answer to all these questions. An inspection of Table 

 I indicates that the chemical structures of most hormonal sub- 

 stances are either unknown or only partially defined. If we 

 consider those with known chemical structure we find that even 



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