Some Thoughts on the Biochemistry 

 of the Steroid Hormones 



LEWIS L. ENGEL 



The opportunity to write on the biochemistry of the steroid hor- 

 mones presents an occasion to examine past progress, which has been 

 most dramatic; to consider current interests; and to speculate upon 

 future directions for this intriguing field. There are relatively few 

 fields of contemporary biochemical interest in which the interaction 

 of the work of organic chemists, biochemists, and clinical scientists 

 has proved so fruitful. This continual interplay of interests and of 

 attacks has made possible impressive progress in the last two and one- 

 half decades. The three major problems in steroid-hormone biochem- 

 istry which are of principal interest to the biochemist are biosynthesis, 

 catabolism, and mechanism of action. The general, overall pathways 

 of biosynthesis of the steroid hormones are now reasonably well under- 

 stood, although, of course, many details and individual reactions re- 

 quire further elucidation. It now seems highly probable that the 

 formation of the steroid hormones in the animal body proceeds from 

 acetate via cholesterol, or some substance closely related to cholesterol, 

 to the individual hormones. 



Thus, reductive condensation of acetate moieties to cholesterol is 

 followed by oxidative removal of six or all eight carbons of the side 

 chain and introduction of oxygen functions at key positions in the 

 nucleus. In the case of the estrogens, ring A is aromatized with elimi- 

 nation of carbon 19. Although a biosynthetic pathway independent 

 of cholesterol has been postulated, no unequivocal evidence for such 

 a pathway has yet been adduced. 



The catabolism of the steroid hormones, insofar as it leads to recog- 

 nizable metabolites, i.e., those which still retain an intact steroid 

 nucleus, may be a reductive or an oxidative process, or both. Double 

 bonds at ring junctions and carbonyl groups may be reduced to the 



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