GREGORY PINCUS 



noted that in the guinea pig the reaction I^II does not appear 

 to occur to an appreciable extent, whereas II— >I occurs readily 

 (2). In all species examined thus far a considerable pro- 

 portion of the transformation products of Cortisol are unknown. 

 In recent studies with C^ ^-labeled Cortisol there have been in- 

 dications that a variety of products may occur, some of which 

 may be nonsteroidal. Furthermore, there are indications of 

 species differences in the mode of metabolism ; thus in the rat and 

 mouse there is considerable excretion of fecal metabolites, 

 whereas in man up to 80% of the 4- G^ ^-Cortisol radioactivity has 

 been excreted into the urine (5). 



In the case of the steroid hormones the search for metab- 

 olites generally has paralleled what has been described for 

 Cortisol. No complete balance sheet is possible but a variety of 

 transformation products are well established. When we con- 

 sider the hormones the chemical nature of which is less well es- 

 tablished, our knowledge of their fate in the body is meager 

 indeed. Thus it is known that certain anterior pituitary hor- 

 mones disappear extremely rapidly from the blood stream, but 

 where they go and what their chemical fate is, remains a mys- 

 tery. 



Having discussed in summary fashion the major biochemi- 

 cal problems of a fairly intensively investigated hormone, I 

 think I have made evident some of the hiatuses in our knowledge 

 concerning it. Similar considerations apply to other hormonal 

 substances. What they do is known to a greater or lesser extent, 

 but it may be safely stated that there is no complete knowledge of 

 all the actions of any single hormone. How they do it is for the 

 most part a mystery, at least in the ultimate sense of mechanism 

 of action. And the biochemical fate of most of the hormones is 

 unknown, and for those concerning which we have some specific 

 information a complete balance sheet has not been established. 



Synergism and Antagonism 



There are other aspects of hormone biochemistry not en- 

 compassed by our five leading questions. For example, sub- 



188 



