THE ADRENAL GLAND 273 



urinary nitrogen excretion. It causes glycosuria, sodium retention, and 

 increased potassium excretion in rats and has an effect identical with 

 that of the corticosterones in reducing the number of circulating lympho- 

 cytes. All these effects can be evoked in the hypophysectomized animal 

 in which no other known agent will cause an increased adrenal cortical 

 secretion. So far as is known at the present time the only effect of this 

 hormone is the stimulation of the secretory function of the adrenal 

 cortex. 



But while the identification and isolation of this trophic hormone 

 answers the question of the agent responsible for an increased adrenal 

 cortical secretion, it merely transfers to the anterior lobe of the pituitary 

 the question of the mechanisms that cause this gland to secrete the 

 agent that is essential for an increased hormone production by the adre- 

 nal cortex. Are these mechanisms of nervous or humoral origin? 



Before such a question can be tested experimentally it is necessary 

 to have available some method of determining the rate of secretion of 

 the adrenal cortical hormones. When we began our work, the available 

 methods for following adrenal cortical secretion were not very suitable 

 for studies in which small animals were to be exposed to a variety of 

 conditions. Those that had been used included (a) the determination 

 of "cortin" excretion in the urine by chemical or biological methods. 

 This is obviously impracticable in small animals, although in man it has 

 been successfully used by Browne and Venning and others to show that 

 trauma or infections increase the secretory rate. The second method 

 (b) used direct determinations of cortical hormone by biological means 

 in the blood of the adrenal vein. This method, applicable only to dogs 

 under anesthesia, had been used by Vogt (5) in England. It has yielded 

 important information, including the demonstration that epinephrine 

 injection is followed by an enhanced output of the hormone. The third 

 group (c) consisted of methods based on the actual content of hormone 

 in the gland. These are not practical at the present time. 



Consideration of the question led to the suggestion that some lipid 

 constituent of the gland might vary with different degrees of its activity. 

 It was known that the stainable lipid of the gland decreased under con- 

 ditions associated with increased secretion, and there was some evidence 

 that the cholesterol content of the gland underwent similar changes. 

 Indeed there was a voluminous literature on this last subject, containing 

 many contradictions and expressions of opinion as to the relation of 

 adrenal cholesterol to the intermediary metabolism of this substance in 

 the rest of the organism. The general idea that cholesterol might be the 



