520 Pituitary and Carbohydrate Metabolism 



that in all these cases, however, failure of gluconeogenesis could explain the 

 findings in both types of animal. 



Additional support to the idea that the anterior pituitary acts through its 

 adrenocorticotrophic relationship is given by the failure of certain effects of 

 APE to be evident in adrenalectomized animals. The diminution of the 

 diabetogenic effects of APE is quite striking, although the effect may not be 

 altogether absent and the maintenance of high blood-sugar levels by APE 

 after adrenalectomy has been reported in some species. The ketogenic effect 

 of APE has also been considered to be absent after adrenalectomy. However, 

 it has been shown recently that ketonemia is in fact produced, although not 

 always to the same extent as in normal animals, and that ketonuria is not 

 found because the renal threshold for acetone bodies is not usually ex- 

 ceeded.^"' ^^ Also, fat accumulation in the liver after APE does not occur in 

 adrenalectomized animals.^"'^ 



There are also similarities between the effects of certain APE, particularly 

 those rich in adrenocorticotrophic factor, and of adrenal cortical preparations. 

 The diabetogenic effects of cortical hormones have been demonstrated in 

 partially pancreatectomized normal, adrenalectomized, and hypophysecto- 

 mized animals. Glycosuria and nitrogen excretion are much increased, roughly 

 in proportion to the amount of cortin given, and ketonuria is also increased. 

 In phlorizinized adrenalectomized or hypophysectomized rats, cortical com- 

 pounds also effectively restore glucose and nitrogen excretion to normal^ as 

 APE does also in hypophysectomized animals. In most of these experiments 

 with cortical hormone there is evidence of increased gluconeogenesis only, 

 and not of any depression in carbohydrate oxidation. 



Contrainsulin effects of cortical extracts and of adrenotrophic APE were 

 demonstrated by Jensen and Grattan*^"' and others.'* In all cases, increased 

 supplies of carbohydrate and elevation of liver glycogen, as a result of gluco- 

 neogenesis following administration of the cortical hormone, satisfactorily 

 explained the anti-insulin effects of these substances. 



Finally, cortical hormones administered in quantity to fasted normal, hy- 

 pophysectomized, or adrenalectomized animals increase the liver glycogen, 

 the blood sugar, and often the muscle glycogen, evidently by increasing 

 gluconeogenesis, and these extracts may also appear to diminish carbohydrate 

 oxidation in glucose-fed rats."" The effects are similar in a general way to 

 those of APE, and particularly to the effects of adrenocorticotrophic extracts, 

 but, as will be discussed shortly, there also exist certain differences between 

 the effects of the hormones of the two glands. 



All of these points, then, indicate that some, at least, of the actions of the 

 anterior pituitary on carbohydrate metabolism are mediated through the 

 adrenal cortex. However, increasing evidence is accumulating that the pitui- 

 tary may have actions on metabolism not so mediated, but instead carried out 

 directly, or perhaps in some instances through some sort of synergism between 



