722 VII. LIPID DISTRIBUTION IN SPECIFIC TISSUES 



secreted into the blood stream and subsequently excreted in the urine 

 whenever the metabolism of fat was accelerated. 120 Several workers proved 

 that the production of ketone bodies is accompanied by an increased amount 

 of liver fat, 118 ' 124 ' 127,128 as well as by a depression of blood lipids, 129 and also 

 by a lowering of the R.Q. 130-132 



The principle in the anterior lobe responsible for this effect has been re- 

 ferred to as the "ketogenic" or "diabetogenic" hormone. The mechanism 

 by which it brings about its action is uncertain. Although Bloor 49 sug- 

 gests that the ketogenic action must be entirely related to its retardation 

 of carbohydrate metabolism and especially of protein metabolism, and not 

 to its action as a fat-metabolizing hormone, certain experimental data 

 render this conclusion open to question. Since it is known that only a slight 

 ketonuria develops in the rat after prolonged fasting, 133-135 the high level 

 of ketonuria evoked by the injection of the hormone cannot be attributed 

 entirely to the removal of carbohydrate. Moreover, there is no experi- 

 mental evidence that a suppression of protein metabolism occurs, since 

 urinary nitrogen was found to be essentially normal in the rat when a 

 marked ketonuria was produced by the injection of the anterior pituitary 

 extract. 122 On the other hand, the ketonuria is not produced in fed 

 rats, 120,136 and it is likewise counteracted by the administration of small 

 amounts of glucose. 122 These facts lead the present author to conclude 

 that the action of the extract of the anterior pituitary lobe in producing 

 ketonuria is to be traced to a direct action on fat. 



According to Greaves et al. lS7 the ketogenic hormone is a heat-labile, non- 

 diffusible compound which is salted out by the addition of ammonium sul- 

 fate to make a 0.2 to 0.45% solution, or by full saturation with sodium 

 chloride. Butts and co-workers 122 likewise demonstrated that the hor- 

 mone is heat-labile and precipitable by alcohol ; moreover, it was shown to 

 be completely inactive when given orally. Although the isoelectric point is 

 at pR 6.7 to 5.75, the hormone is more stable at a pH. of 9.5 to 11. The 

 unit has been defined as the quantity which causes a lowering of the R.Q. 



129 O. B. Houchin and C. W. Turner, Endocrinology, 24, 638-644 (1939); 25, 216-220 

 (1939). 



130 R. E. Fisher and R. I. Pencharz, Proc. Soc. Exptl. Biol. Med., 34, 106-107 (1936). 



131 R. E. Fisher, J. A. Russell, and C. F. Cori, /. Biol. Chem., 115, 627-634 (1936). 



132 H. S. Meyer, L. J. Wade, and C. F. Cori, Proc. Soc. Exptl. Biol. Med., 36, 346-348 

 (1937). 



133 J. S. Butts and H. J. Deuel, Jr., J. Biol. Chem., 100, 415-428 (1933). 



134 H. Levine and A. H. Smith, /. Biol. Chem., 75, 1-22 (1927). 

 136 G. T. Cori and C. F. Cori, /. Biol. Chem., 72, 615-625 (1927). 



136 R. A. Shipley and C. N. H. Long, Biochem. J., 32, 2242-2256 (1938). 



137 J. D. Greaves, I. K. Freiberg, and H. E. Johns, /. Biol. Chem., 133, 243-259 (1940). 



