Studies with Deuterium Steroids 29 



It is already clear from the many studies of Rittenberg and 

 his associates that deuterium is an excellent tracer in bio- 

 chemical studies and this has been confirmed in our investiga- 

 tions. There is little basis for the view still held by some 

 workers that the chemically stable hydrogen atoms of organic 

 compounds exchange easily with the medium or participate 

 in obscure reactions which lead to loss of hydrogen without 

 essential alteration of the molecule. On the contrary, it is 

 important that even when a chemically labile deuterium 

 atom is present in an intermediate, this isotope is not neces- 

 sarily lost in a metabolic transformation and, indeed, a high 

 percentage is frequently retained in the excretory end product. 

 The use of this element as a tracer is therefore fully justified 

 and in many instances can furnish information unobtainable 

 with other tracers. The hormones, moreover, do not suffer 

 extensive dilution from either endogenous production or 

 from the diet, and thus in many instances it is not obligatory 

 to work with extremely low concentrations of the isotope^^ 

 Finally, there has accumulated a considerable body of know- 

 ledge of the metabolism and fate of some of the important 

 steroid hormones and this has served as a guide and control 

 of these initial studies (Dobriner and Lieberman, 1950). 



Many deuterium-labelled steroids can be prepared by 

 reduction of an unsaturated compound with the hydrogen 

 isotope, and a properly chosen intermediate can furnish a 

 number of compounds for metabolic study. By hydro- 

 genating lithochol-11-enic acid in solution in acetic acid-c? 

 with deuterium gas in the presence of a platinum catalyst, 

 the saturated acid with 4 • 03 atoms per cent excess deuterium 

 was obtained. This was converted to pregnanolone by known 

 methods and the pregnanolone served as a good intermediate 

 for the preparation of the steroid hormones and metabolites 

 shown in Fig. 1. The products served nicely for tracer 

 experiments since they contained a useful concentration of 

 isotope and their chemical preparation was relatively simple. 



We sought, however, a more generally applicable reaction 

 which could be used with substances closely related chemically 



