THE PITUITARY GROWTH HORMONE 365 



that insulin is a protein-anabolic hormone (Krahl, 1956). These con- 

 siderations, joined with the numerous observations that the anabolic 

 properties of growth hormone are not demonstrable in the diabetic 

 animal, have led to the suggestion that growth hormone may exert its 

 physiological eflFects by stimulating the pancreas' secretion of insulin or 

 by otherwise increasing the availability of insulin to the tissues (see 

 Ketterer, Randle, and Young, 1957, and de Bodo and Altzuler, 1958, 

 for review). Clearly, in the systems where growth hormone is added 

 to muscle tissue in vitro, the stimulation of amino-acid transport or in- 

 corporation into protein cannot be explained in terms of increased 

 pancreatic insulin secretion. It has been argued, however (Ottaway, 

 1953), that the insulin-like activity of growth hormone in vitro could 

 be due to a release of bound insulin from the tissue. To test this hy- 

 pothesis, Manchester and Young (1959a) prepared an insulin anti- 

 serum which completely abolished the ability of insulin to stimulate 

 the incorporation of labeled glycine into the protein of diaphragms 

 from hypophysectomized rats in vitro. This antiserum, however, in no 

 way inhibited the action of growth hormone in the same system, which 

 suggests that the eflPect of growth hormone on amino-acid incorporation 

 is a direct one on the tissue and, though in all probability requiring the 

 presence of insulin in a permissive sense, is not mediated by it (see 

 also Scow and Chernick, 1960 ) . 



Of particular interest in this connection is a recent prehminary 

 report by Huggins and Ottaway (1960) that the further fractionation 

 of a highly purified growth-hormone preparation permitted the separa- 

 tion and purification of a peptide with high insulin activity, as assayed 

 in vitro. The confirmation of these findings would do much to clarify 

 the significance of the many similarities between the metaboHc actions 

 of growth hormone and insulin. 



Growth hormone and fatty acid metabolism. The increased deposi- 

 tion of protein (as determined by carcass analysis) that results from 

 growth-homione administration is accompanied by a concomitant loss 

 of fat. Further, growth-hormone administration leads to a reduction in 

 the respiratory quotient, a mobilization of fat to the liver, and an in- 

 creased ketogenesis. These widely confirmed observations have led to 

 the generally accepted view that growth hormone has a profound in- 

 fluence on lipid metabolism, and, more specifically, that the hormone 

 accelerates fat mobilization and oxidation (see reviews by Weil, 1955, 

 and de Bodo and Altzuler, 1957 ) . 



Renewed interest in the influence of growth hormone in lipid 

 metabolism has been stimulated by the recent appreciation of the 

 metabolic significance of the proportionally small non-esterified or 

 free fatty acid ( FFA ) fraction of the circulating lipids ( see Frederick- 

 son and Gordon, 1958). These free fatty acids, by virtue of their rapid 



