180 CONTROL MECHANISMS IN CELLULAR PROCESSES 



Biological Implications 



The TPNH-DPN transhydrogenase reaction catalyzed by the pla- 

 cental enzyme is mediated by concentrations of estradiol- 17yS as low 

 as 10^*' M and by even lower levels of equilin and eqnilenin (Hol- 

 lander, Nolan, and Hollander, 1958). This concentration of estra- 

 diol-17yS may be regarded as "physiological" in the light of recent 

 experiments of Jensen and Jacobson ( 1960) . These workers showed 

 that following the administration of 0.1 fig of estradiol-17/3-6, 7t to 

 immature rats, this estrogen is concentrated in the uterus and vagina. 

 Maximal incorporation was observed from 2 to 6 hours after injec- 

 tion of the tritiated estrogen, at which time the concentration of 

 estradiol-17/3 in the uterus (assuming equal distribution between 

 the tissue and its intra- and extracellular water) was of the order of 

 10~"^ M. Thus, activation of transhydrogenase reactions catalyzed 

 by the placental enzyme is demonstrable with concentrations of 

 estradiol-17yS which fall within the range of those at which the hor- 

 mone promotes the growth of the rodent uterus. It is of interest 

 that Jensen and Jacobson ( 1960 ) found that from 2 to 6 hours after 

 its administration, most of the tritiated estradiol-17yS was present in 

 the uterus in a free, ether-extractable form. Very little protein- 

 bound, or water-soluble, radioactivitv could be detected. Jensen and 

 Jacobson ( 1960 ) also showed that, under these experimental condi- 

 tions, the level of radioactive estrone in the uterus was less than 5 

 per cent of that of estradiol-17;S. 



The well-established division of metabolic labor between DPN 

 and TPN (cf. Klingenberg and Blicher, 1960) has led to many sug- 

 gestions that enzymes which catalyze the transfer of hydrogen be- 

 tween TPN and DPN may be of central importance in the regulation 

 of cell metabolism. The brilliant studies of Colowick and Kaplan 

 have shown that Pseudomonas fluorescens (Colowick, Kaplan, Neu- 

 feld, and Ciotti, 1952) and the mitochondria of some animal tissues 

 (Kaplan, Colowick, and Neufeld, 1953; cf. Ball and Cooper, 1957; 

 Humphrey, 1957) contain pyridine nucleotide transhydrogenases' 

 which catalvze the direct transfer of hydrogen between TPNH and 

 DPN. These transhydrogenases do not require a low-molecular 

 weight cofactor, and their action almost certainly does not involve 

 an intermediary hydrogen carrier. The transhydrogenases of animal 

 tissues are firmly bound to cytoplasmic particles (cf. Stein, Kaplan, 

 and Ciotti, 1959). There is evidence that the mitochondrial pyri- 



