160 III. OXIDATION AND METABOLISM 



of the foodstuffs. Thus, ckiring periods of stress, such as during fasting, 

 variations in response become evident, because of the particular enzyme 

 systems present in the animals as a result of their previous adaptation. 



(/) Hormones as Related to Ketonuria. Many hormones influence the 

 degree of ketonuria of the animal. The profound effect of sex on suscepti- 

 bility to fasting ketonuria is undoubtedly based upon a hormonal relation- 

 ship. The fact that the high level of ketonuria of the female is abolished 

 after ovariectomy would seem to indicate that the hormone responsible 

 for the ketonuria is produced in the ovary, either directly or due to external 

 stimulation. The pancreatic hormone, insulin, is another substance which 

 is indirectly related to ketonuria by virtue of its regulation of carbohydrate 

 metabolism. Following pancreatectomy, ketonuria usually occurs con- 

 comitantly with the glycosuria. 



A third hormone which appears to be directly concerned with ketosis is 

 produced in the anterior lobe of the hypophysis; it is frequently referred 

 to as the ''ketogenic" or "diabetogenic" hormone, since the injection of this 

 substance is usually followed by ketonuria. Anselmino and Hoffmann^^^ 

 were the first to demonstrate, in 1931, that extracts of the anterior lobe of 

 the pituitary provoked ketonemia when injected into rats. It was sub- 

 sequently reported^^* that such ketogenic extracts also produced fatty 

 infiltration of the liver; it was likewise claimed that they regulated the 

 level. Many observers^^^"^^^ have confirmed the lipogenic effect of the 

 extracts of the anterior lobe, as well as their effects on ketonuria. Since 

 the ketonuria following injection of the extract of the anterior lobe of the 

 pituitary is accompanied by a fatty infiltration of the liver, it is believed 

 that carbohydrate combustion is retarded or completely abolished under 

 these conditions, with the result that fat serves as the sole source of energy. 

 The development of ketosis is therefore the result both of the increased 

 level of fat oxidation and of the failure of carbohydrate to act ketolytically. 

 This suggestion is in harmony with the observation that the ketogenic 

 hormone provokes a ketonuria in fasted and possibly also to a lesser extent 



*83 K. J. Anselmino and F. Hoffmann, Klin. Wochschr., 10, 2380-2383 (1931). 

 *84 K. J. Anselmino, F. Hoffmann, and E. Rhoden, Arch. ges. Physiol. (Pfliiger's), 237, 

 515-516 (1936). 



^85 C. H. Best and J. CampbeU, /. Physiol., 86, 190-203 (1936). 



«6 P. T. Black, J. B. Collip, and D. L. Thomson, J. Physiol, 82, 385-391 (1934). 



^" V. G. Foglia and P. Mazzocco, Compt. rend. soc. biol., 127, 150-152 (1938). 



«8E. G. Fry, Endocrinology, 21, 283-291 (1937). 



489 E. M. MacKav and R. H. Barnes, Am. J. Physiol, 118, 525-527 (1937). 



"o A. H. Neufeld and J. B. Collip, Endocrinology, 25, 768-774 (1939). 



"1 J. H. Burn and H. W. Ling, Quart J. Pharm. and Pharmacol, 2, 1-16 (1929). 



"2 J. S. Butts, C. H. Cutler, and H. J. Deuel, Jr., J. Biol Chem., 105, 45-58 (1934). 



