§ 4.231 MESODERMAL ENDOCRINE GLANDS OE VERTEBRATA 147 



histamine and the cortical hormone, and varying the time interval 

 between the two injections, it can be shown that in 10 sec the 

 histamine has already exerted almost as great an effect upon the 

 release of ACTH and the reduction of ascorbic acid, as it docs in 

 the absence of any cortical injection (histamine alone, Fig. 4-10). 

 After only 3 sec there is practically no blocking effect by the 

 cortical hormone, so that it can be concluded that the histamine has 

 already produced some effect upon the hypophysis. The action is 

 in fact almost as rapid as that of the cortical hormone itself, and 

 takes little longer time than the blood needs to circulate from the 

 point of injection to the hypophysis. This does not, however, 

 solve the question of whether these substances act upon the 

 hypothalamus of the brain, rather than upon the hypophysis 

 direct. 



It is interesting to note that the time required for adrenaline to 

 produce a similar reaction in the hypophysis is considerably longer 

 than that for histamine (Fig. 4-11). Adrenaline cannot therefore 

 be held to act as a necessary intermediary between the noxious 

 stimulus and the adenohypophysis from which it calls forth the 

 ACTH secretion (Munson and Briggs, 1955). 



The rate of secretion of both ACTH and of the cortical hormone 

 can also be measured directly in the blood. ACTH can be detected 

 in circulation soon after the application of any noxious stimulus ; 

 ACH can be detected in the adrenal vein within a few seconds of 

 the injection of ACTH. But this method of assay is not wholly 

 satisfactory, since both hormones are destroyed in the tissues 

 within a few minutes of their release. It has been estimated that 

 ACTH is reduced to about half its previous concentration in 

 2 to 5 min in the blood ; but its fate is somewhat uncertain. It is 

 not excreted in the urine, but accumulates in even larger quantities 

 in the kidneys than in the adrenal cortex. It is inactivated after 

 incubation with kidney or liver tissue in vitro ; yet the removal of 

 both kidneys and most of the liver does not render an ACTH 

 injection any more effective than before, in reducing the ascorbic 

 acid contents of the adrenal cortex, possibly because even small 

 doses can produce a maximal effect (Astwood, 1955). In the dog, 

 the action of ACTH, in increasing ACH secretion, persists for 

 about 15 min after injection; and even an hour after removal of 



