INTRODUCTION 11 



in opposite directions. Such physiologic bipolarity of the cell is associated 

 with a morphologic bipolarity in that special activity may be demon- 

 strated in the opposite zones of the cell. Thus mitochondria may be 

 demonstrated in both the supranuclear and infranuclear zones, whereas 

 in the ordinary secreting cell one zone only is seen. Hence from a, mere 

 study of the microscopic picture of the individual cell, to determine 

 whether it is oriented as regards nucleus and granular inclusions toward 

 ducts or toward the capillaries, it is often possible to decide whether 

 the structure has an ordinary external secretion or an internal secretion 

 proper. In general, then, it may be stated as a necessary condition 

 before a structure can be regarded as having an endocrin function that 

 it must be made up of cellular elements, that the cells show morphologic 

 evidence of secretory activity, and that the cells have a definite orienta- 

 tion toward the blood or lymph channels. 



Chemical Condition. Every product of secretion, external or internal, 

 is the result of chemical processes within the cells. The product must 

 be recognizable by its chemical characteristics and be identified as an 

 entity, both in the cell itself and in the efferent vessels. In only a 

 few instances have the characteristic products of the endocrin tissues 

 been thus demonstrated within the cells, That epinephrin so exists in the 

 suprarenal medulla has been proved. In the thyroid cells also a char- 

 acteristic colloid is found and this has been demonstrated in the efferent 

 vessels. The relation of this colloid, however, to the hormone proper 

 has not been definitely determined. In case of the other endocrin organs 

 little progress has as yet been made in satisfying the logical requirement 

 postulated in the caption of this paragraph. 



Physiological Condition. Fulfillment of this third condition, as pre- 

 viously stated, requires the demonstration of a specific substance in the 

 efferent vessels by means of various physiological reactions when blood or 

 lymph is injected into a second animal. Obviously, to permit such demon- 

 stration the substance in question must maintain its identity in the blood 

 stream long enough to permit it to reach the capillary circulation of 

 the effector mechanisms through which the activity is manifested. The 

 dilution factor may interpose a serious difficulty. In the case of epi- 

 nephrin the substance can be obtained in sufficient concentration in the 

 lumbo-adrenal veins to permit the demonstration of its presence by several 

 methods. Even when it is diluted by the total blood volume of the re- 

 cipient test animal, pharmacodynamic effects can be seen in a number of 

 different organs. 



Observations made in Cushing's laboratory have been widely quoted 

 as showing the possibility of demonstrating the active principle of the 

 pituitary organ in the cerebrospinal fluid into which it has been supposed 

 to be discharged. Recently, however, upon careful restudy of the problem, 

 Jacobson, one of the original observers, has reached the conclusion that 



