176 CONTROL MECHANISMS IN CELLULAR PROCESSES 



tions. Neither estriol nor 17a-ethynylestradiol-17/3 reduces DPN in 

 the presence of the placental enzyme, yet both of these substances 

 stimulate the TPNH-DPN exchange (Villee and Hagerman, 1958; 

 Hollander, Nolan, and Hollander, 1958 ) . However, the latter trans- 

 hydrogenase reaction was stimulated by these two steroids only in 

 relatively high concentration, and the activity of 17a-ethynylestra- 

 diol-17^ could be accounted for if it was assumed that the sample 

 contained 1 per cent by weight of either estradiol-17yS or estrone as 

 an impurity (cf. Talalay and Williams-Ashman, 1960). According 

 to Hollander, Nolan, and Hollander (1958), 16-ketoestradiol-17y8 

 and 16-ketoestrone do not stimulate the transhydrogenase reaction. 

 Yet 16-ketoestrone is hvdrogenated at about one-fourth the rate of 

 estrone (Langer, Alexander, and Engel, 1959). But strangely 

 enough, 16-ketoestradiol-17;S will not reduce DPN in the presence of 

 the placental enzyme at pH 9.2. This suggests that the equilibrium 

 for the reaction of 16-ketoestrone with DPNH is very much in favor 

 of complete reduction of the steroid and quite different from the 

 equilibrium for the oxidation of estradiol-17yS. If this is the case, 

 one would not expect either 16-ketoestrone or 16-ketoestradiol-17y8 

 to act as efficient mediators for the TPNH-DPN exchange via a 

 mechanism which involved oxidoreduction of the steroids. 



Interconversion of Hydroxy- and Ketosteroids 



Hollander, Hollander, and Brown (1959a) found that when the 

 placental enzyme catalyzed the TPNH-DPN transhydrogenase reac- 

 tion in the presence of estradiol-17/3-i6'-C", a steady state is soon 

 achieved in which the ratio of estrone/estradiol-17/3 is aproximately 

 3. During the course of transfer of hydrogen from DPNH to acetyl- 

 pyridineDPN, estradiol- 17yS-6,7,f becomes interconverted with es- 

 trone (Talalay and Williams-Ashman, 1960). These experiments 

 suggest, but do not prove, that estradiol-17^ undergoes alternate oxi- 

 dation and reduction when it mediates transhydrogenase reactions 

 catalyzed by the placental enzyme. 



Stereospecificity of Hydrogen Transfer 



In experiments using DPN-nicotinamide-4-# and TPN-nicotina- 

 mide-4-f, Jarabak and Talalay (1960) showed that the dehydroge- 

 nation of estradiol-17yS by the placental enzyme occurs with transfer 



