GREGORY PINCUS 



smaller yield. The acid test of the scheme for the interconversion of 

 testosterone and androsterone would be met by certain identification 

 of the intermediaries after administration of active hormone. Finally, 

 Dorfman has reported a conversion of exogenous testosterone to etio- 

 cholan-3-ol-17-one and to isoandrosterone in man. To account for 

 these reduction products several other mechanisms are indicated (7). 



While testosterone has generally been recognized as the true 

 hormone of the testis, certain species may produce other, now un- 

 known, testoids. For example, Ruzicka was unable to obtain testos- 

 terone from hog testis tissue, and Hirano has reported the isolation 

 of testalolone and possible related steroids. If we want to ascertain 

 the fate of steroid hormone produced by the testis, a more complete 

 knowledge of just what the testis does produce is obviously required. 



The course of conversion of the natural folliculoids (the Cis 

 steroid hormones) indicated above appears to be well established. 

 In the rabbit /3-estradiol is produced, whereas in man, the monkey, 

 and probably also in the rat and guinea pig a-estradiol is a conversion 

 product of estrone. Estriol is indicated as a metabolite in the various 

 animal species, but only in man has it been isolated as a urinary end 

 product following administration of estrone. 



In all species investigated, the recovery of known catabolites 

 from the urine after the administration of estradiol or estrone to the 

 intact animal is low indeed, ranging from 1-2% to at most a possible 

 15% of the administered hormone. The fate of the balance has been 

 the subject of some investigation. It has been claimed that the 

 missing material undergoes an enterohepatic circulation much like 

 that of the bile acids. This claim requires more evidence, but there 

 is no doubt that a good amount of foUiculoid appears in the bile after 

 estradiol and estrone injection. Dr. J. Schiller and the writer have 

 recently shown that the removal of most of the liver of female rats 

 results in a large increase of urinary folliculoid. The injection of 

 estrone into such partially hepatectomized rats leads to the recovery 

 in the urine of folliculoids accounting for about 60% of the administered 

 hormone. From female rats with intact livers, 13%, at most, of ad- 

 ministered estrone can be recovered. Zondek has postulated a liver 

 estrinase, for inactivation can be oi«erved in vitro on incubating fol- 

 liculoid hormones with liver mash. Attempts to isolate a phenolase 

 that might be responsible for such inactivation have been unsuccessful. 



3H 



