GREGORY PINCUS 



method of Bloch using deuterized cholesterol is limited by the need 

 lor relatively large amounts of the steroid products for mass spectros- 

 copy. Probably it is for this reason that only pregnanediol has been 

 identified as a transformation product of deuterized cholesterol. No 

 similar study has been carried out on other postulated intermediaries. 

 It is to be hoped that the development of micro methods will make 

 possible more extensive utilization of the isotope technique. Similarly, 

 in tracing the synthesis of steroids from postulated triose precursors, 

 the use of isotopes is clearly indicated. 



Another approach to anabolic processes, particularly in mam- 

 mals, involves studies of the metabolism of precursors in vitro. The 

 perfusion of active steroidogenic organs should provide useful informa- 

 tion. On the basis of data derived from perfusion studies one might 

 attempt the isolation of the enzyme systems concerned with the ob- 

 served transformations. It is notable, however, that Danby, who 

 obtained increased testoid activity on perfusion of the bull testis with 

 dehydroisoandrosterone, was unable to observe any increase at all on 

 incubating dehydroisoandrosterone with testis mash. 



One further note on the problem of steroid hormone synthesis 

 seems pertinent here. Emmens has made a useful distinction between 

 estrogens and proestrogens (folliculoids and profolliculoids in our 

 terminology). In dealing with substances particularly of the stilbene 

 series, he finds certain compounds which on systemic injection are 

 much less active per milligram than when applied intravaginally. 

 These are true estrogens because their action on the susceptible end- 

 organ requires much less material with direct application. Calling 

 the systemic median effective dose S and the median effective local 

 dose L, Emmens finds true estrogens (e. g., estrone, diethylstilbestrol) 

 give in spayed mice an S/L ratio of 50 or more. Proestrogens give an 

 S/L ratio approximating unity (e. g., a-phenylstilbestrol, triphenyl- 

 ethylene). SegalofT has shown that three proestrogens (triphenyl- 

 ethylene, triphenylchloroethylene, and 9,10-di-n-propyl-9,10-dihy- 

 droxy-l,2,5,6-dibenzanthracene) are definitely potentiated after in- 

 trasplenic injection (with the spleen in situ). Passage through the 

 hepatic portal system increased their activity some three to six times. 

 Since injection into the isolated spleen does not effect such potentia- 

 tion, it is probable that the liver converts these substances to more 

 active compounds. The possibility that the liver may play a role in 



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