222 



G. Nichols, jr. 



one's favorite hormone that it is difficult to settle upon a suitable example! The one I 

 have selected, drawn from some experiments by Widnell and Tata (1963), concerns 

 the action of triiodothyronine in vivo on metabolic activities in fractions of liver 



^^00 



^ 100 



Hormone M " 70^ 



Fig. 4. Inhibition of glutamic dehydrogenase acti- 

 vity by various estrogenic steroids, measured as 

 the change in O.D. due to reduction of DPN, 

 2X]0~' M, present in the system. (From Tompkins 

 and Yielding 1964, reproduced with the permis- 

 sion of the publishers.) 



50 



^ 20 W SO 80 too 



Time after T^ \\,v 



Fig. 5. An idealized diagram showing the sequential chan- 

 ges in activity of various nuclear and cytoplasmic meta- 

 bolic processes in liver at various times after a single 

 injection of triiodothyronine into thyroidectomized rats. 

 (From Tatv 1964, reproduced with the permission of the 

 publisher.) 



taken from thyroidectomized rats. Fig. 5 was selected (Tata, 1964) because it shows 

 so clearly the time sequence involved — from the earliest effect on nuclear RNA 

 polymerases through the synthesis of new protein and the availability of additional 

 cytochrome activity to the final disappearance of each change. Moreover, these 

 experiments emphasize that the place where such hormonal effects should be sought is 

 at the earliest point in the metabolic system — in this case the transcription of 

 information from DNA by RNA synthesis. Evidence (often derived from studies 

 with various metabolic inhibitors) of similar sorts of effects produced by steroids, 

 insulin, and various trophic hormones is rapidly becoming available (Litwack and 

 Kritchevsky, 1964; Tompkins and Maxwell, 1963). 



Before leaving this area one more point should be made. "While current fashion 

 tends to dictate that an effect on the "interpretation" of DNA is the ultimate in 

 "molecular" endocrinology behind which it Is not necessary to look for earlier or 

 more basic effects, it must be remembered that such changes — be they qualitative or 

 quantitative — must involve changes in enzyme activity and hence perhaps protein 

 synthesis. Which came first, change in DNA or change in protein may well be a 

 question, therefore, which is far from being solved! 



The present status, then, can be summarized quite simply: Knowledge of cell 

 physiology, structure, and metabolic pathways permits the prediction of sites and 

 modes of action of hormones on purely theoretical grounds — a process which leads 

 to the conclusion that hormones act in only 3 ways at the molecular level. Moreover, 

 the application of these ideas to studying the effects of a variety of hormones on 



