STEROID HORMONES 



would appear to be from I — > II -^ III. The conversion of I — > II 

 has been accomplished by bacteria. It is interesting that A^-prcg- 

 nenolone has been obtained as a naturally occurring substance thus 

 far only from testis tissue; yet progesterone is a female hormone par 

 excellence. Patient search for pregnenolone in female tissues appears 

 desirable. 



Among the naturally occurring 19-carbon steroids, A^-dehydro- 

 isoandrosterone (formula IV) corresponds to A*-pregnenolone. We 

 would expect it, therefore, to be the immediate precursor of testos- 

 terone (V) (the primary testis hormone). That the transformation 

 of IV -^ V takes place appears probable on the basis of Danby's data 

 for the perfusion of testis tissue with IV. The resulting high testoid 

 activity in the perfusate might well be attributed to V which is the 

 most active of all testoid steroids. That VI cannot arise directly from 

 IV may be deduced from the fact that Dorfman and Hamilton (2) 

 were unable to recover VI from the urines of eunuchoid men after 

 the administration of dehydroisoandrosterone. 



OH 



O 



II 



/^ 



HO- 



(IV) 



Dehydroisoandrosterone 



HO- 



A/ 



Testosterone 



(VI) 



Androsterone 



The light thrown on the nature of the immediate precursors of 

 the sex hormones is meager indeed, but in the field of the adreno- 

 corticosteroid hormones the darkness is almost total. We know only 

 that these hormones from adrenal tissue are accompanied by inactive 

 steroid substances which might be converted to active hormone by 

 appropriate oxidation and reduction. It would be most instructive 

 to perfuse such substances through adrenal glands to see if they are 

 convertible to active hormone. 



While one may thus indicate possible chemical precursors of 

 the known steroid hormones by administering model substances either 

 iti vivo or in vitro, the normal course of metabolism will continue to be 

 a matter of speculation until a more direct attack is devised. The 



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