370 CELLS, TISSUES, AND ORGANISMS 



per cent would account for its lipolytic efiFect. Such contamination can- 

 not be excluded with certainty in currently available growth-hormone 

 preparations. In point of fact, these findings rather suggest that the 

 striking FFA-mobilizing effect of growth hormone observed in vivo is 

 probably not due to a direct action of the hormone on adipose tissue. 



While growth-hormone administration clearly results in enhanced 

 mobilization of fatty acids from adipose tissue, at least in the fasting 

 animal, its influence on fatty-acid utilization or oxidation is somewhat 

 obscure. As has been mentioned, an impressive body of evidence ac- 

 cumulated over the past 20 years has led to the view that the increased 

 protein deposition in response to growth-hormone administration is 

 effected at the expense of fat oxidation (see de Bodo and Altzuler, 

 1957). The studies of Greenbaum (1953) and Greenbaum and Mc- 

 Lean (1953) have been most influential in this regard. Greenbaum 

 ( 1953 ) made the important observation that when growth hormone is 

 administered to animals on a restricted food intake, they cease to grow 

 after 50 days of treatment, whereas their controls, fed ad libitum, con- 

 tinued to respond. The respiratory quotients of both groups declined 

 after the initiation of growth-hormone therapy. But whereas the R.Q. 

 of the rats fed ad libitum remained depressed, that of injected rats on a 

 limited food intake returned to control levels at the time that they be- 

 came refractory to continued growth-hormone administration. These 

 findings led Greenbaum ( 1953 ) to the conclusion that protein deposi- 

 tion in response to growth hormone can take place only as a result of 

 an increase in fat catabolism, and that when the body's stores of labile 

 fat are exhausted, growth ceases, the primary action of growth hor- 

 mone being the direct stimulation of fat breakdown to provide the 

 additional "calories" to drive protein synthesis. Additional evidence, 

 albeit indirect ( Greenbaum and McLean, 1953 ) , further suggested that 

 growth hormone stimulates fatty-acid oxidation in the liver as well as 

 in extrahepatic tissues. 



The availability of C^'*-labeled long-chain fatty acids made pos- 

 sible a re-evaluation of this problem, using direct criteria of fatty oxi- 

 dation in both in vivo and in vitro systems. Our initial experiments 

 ( Franklin and Knobil, 1961 ) were designed to determine the influence 

 of hypophysectomy and of growth-hormone administration on the con- 

 version of intravenously administered albumin-bound palmitate-1-C^^ 

 to respiratory C^^02. It was necessary, first of all, to establish that this 

 system would reveal physiological changes in the oxidation of fatty 

 acids such as are occasioned by fasting. Figure 7 clearly shows that the 

 intragastric administration of glucose one hour prior to palmitate injec- 

 tion markedly depresses the recovery of C^"* as C^'^Oa when compared to 

 the fasted situation. It would be expected, therefore, that an experi- 

 mental manipulation which materially altered fatty-acid oxidation 



