216 G. Nichols, jr. 



The inevitable result of these early discoveries of different degrees of organ 

 response to various humeral agents was the development of the concept of target 

 organs or systems for each hormone. The classic example of this idea, of course, was 

 its application to the anterior lobe of the pituitary. Once the secretion by the hypo- 

 physis of trophic hormones for other endocrine organs had been shown, several things 

 happened. First, there was an enormous surge forward in understanding the systems 

 for the control of body processes. Not only could endocrinologists use this concept 

 in "reverse" to predict the existence of trophic hormones for each endocrine gland, 

 but in addition it provided the necessary background for the development of the 

 whole theory of feed-back control — a control system now recognized as one of the 

 most fundamental in all living systems. 



However, this target organ concept had another, perhaps less desirable, out- 

 growth. Attention became so closely focused on the effects of each hormone on what 

 appeared to be its particular target that interest in its effects in other areas tended to 

 wane. On the positive side this resulted in the learning of all sorts of details concern- 

 ing the nuances of the action of each hormone. On the negative side, so many details 

 were learned that the study of each hormone's action on its chief target threatened to 

 become a field of specialization in itself while the broader biological influences of 

 these agents tended to be forgotten. 



Two phenomena combined to rescue the field of endocrinology from a limbo of 

 ultimate reductionism. First, as the focus of experimental approaches to endocrine 

 effects improved a number of inconsistencies and even contradictions in the apparent 

 actions of hormones were revealed. These not only further complicated the field but 

 convinced many that a number of effects long accepted as primary were in reality 

 only secondary reflections of effects on more fundamental processes. Second, bio- 

 chemists and cellular physiologists having described a number of metabolic pathways 

 and having found them to be common to many types of cells began to become 

 interested in hormones as potential controls for these processes. 



The outcome of all this has been the development of a new phase in endocrino- 

 logy — one in which the old complexities are beginning to be set aside in favor of 

 concepts of more universal application. Hormones are being classified in terms of 

 chemical structure, and hormone effects are being sought at the molecular rather than 

 the tissue or organ system level. Although so far attention has remained focused 

 largely upon effects on specific target organs, the fact that the systems which are 

 being examined are common to many cells suggests that similar effects are going to be 

 found in many other tissues — even bone. Thus a variety of hormones once thought 

 important in the control of bone metabolism and then ignored in the face of the 

 more dramatic effects of others with clearer skeletal effects promise to become again 

 the subject of fruitful investigation. 



My purpose in this discussion will be to review some of the ideas about cell 

 physiology and general biochemistry upon which this new phase of endocrinology is 

 based and indicate how they can be used to formulate and test hypotheses regarding 

 sites and mechanisms of hormone action. In so doing I shall use bone and bone cell 

 physiology as my model — not because in most cases such effects have even been 

 considered in bone — but rather because it is the tissue of ultimate interest in this 

 symposium and can be used advantageously to indicate how widely these ideas can 

 be applied. At the end I will attempt to indicate how far these ideas have actually 



