88 Essays in Biochemistry 



population with, for example, patients with malignant disease or with 

 collagen diseases. The chemical and physical techniques for carrying 

 out such analyses on relatively small quantities of urinary extracts 

 are now available and can be applied to answer the important ques- 

 tion of whether the abnormality in steroid metabolism in these endo- 

 crine-related diseases can, in fact, be defined by study of urinary 

 excretion products. 



Now that the major pathways in the degradation of steroid hormones 

 to their urinary metabolites have been established, attention is begin- 

 ning to turn to the study of the individual biochemical steps in these 

 pathways. The important technical advances of the last decade, and 

 the increasing availability of a wide variety of steroid compounds, 

 have led to significant advances in this area. The diversity of reac- 

 tions involved in the catabolism of steroids and the high degree of 

 stereochemical specificity in the reactions should make them attractive 

 model systems for enzymologists. Since a wide variety of steroid 

 compounds related to the hormones and differing in structure is avail- 

 able at the present time, opportunity is provided for studying the 

 influence of substituent groups not directly involved in enzymatic 

 transformations and distant from the reacting center of the steroid 

 molecule. Such experiments dealing with substrate specificity should 

 give valuable insight into the number and nature of reactive sites in 

 the enzyme surfaces involved, an insight which could well prove to 

 be applicable to other areas of biochemistry, and which could have 

 important repercussions on our concepts of the mechanisms of enzyme 

 action. 



The discussion above has revolved primarily about the catabolic 

 side of steroid biochemistry. It seems appropriate now to turn to the 

 central question facing us as biochemists and physiologists: viz., what 

 is the mechanism of action of these compounds. The steroid hormones 

 occupy a somewhat paradoxical position, since they can be considered 

 both as essential and non-essential for life. Examination of this 

 apparent paradox may lead to some fruitful speculation concerning 

 the mechanism of their action. It is clear in the case of the gonadal 

 hormones that, while they are not required for the survival of an 

 individual animal, they are required and are essential for the perpetua- 

 tion of the species. In the case of the adrenal cortical hormones, the 

 distinction is not quite so clear. Adrenalectomized animals can be 

 maintained in apparently adequate health provided their diet is sup- 

 plemented by sodium chloride, and provided further that they are not 

 subjected to gross changes in external or internal environment. Thus 



