While it is generally agreed that the adrenal cortices play a prominent role in the adaptation of animals to anoxia, the mechanisms involved in the activation of these glands in this circumstance have not yet been described. It is possible that a fuller understanding of these mechanisms will only be achieved when future investigation reveals a more complete picture of the metabolic function of the adrenals than is available at present. However, the technique of testing the biochemical responses of animals to graded “stress” stimuli may prove itself to be a useful tool in elucidating the mechanism of activation of the adrenals, and subsequently, the function of their hormonal products in metabolism. Exposure of animals to varying degrees of anoxia has proved to be a convenient method of administering quantitatively graded stimuli. Adrenal cortical hypertrophy as a result of anoxia was described by Armstrong and Heim (1938) and others (see Hailman, 1944, for review).

AREVIEW of the literature of adrenal hypertrophy (Tepperman, Engel and Long, 1943) revealed that many of the circumstances in which - such hypertrophy occurs are characterizied by either a relative or absolute increase in the rate of protein catabolism. This fact recurred so insistently that the reviewers have classified the ‘causes’ of adrenal hypertrophy according to the characteristics of their nitrogen economy. On the basis of this suggestion, and in the light of the hypothetical chemical sites of action of the cortical steroids of the corticosterone type, experiments were devised to test the effect of high protein diets on adrenal size. This study was undertaken in an effort to determine whether or notevidence of increased adrenal cortical activity could be secured in animals which were forced to derive a large proportion of their carbohydrate from protein. In addition to morphologic evidence of increased cortical activity

This report consists of three discrete, but interrelated, parts: the first contains a description of the respiratory metabolism of rats with hypothalamic hyperphagia; the second deals with the induction of unusual metabolic patterns in normal, intact rats by the alteration of their feeding habits; and the third is concerned with the site of conversion of carbohydrate to fatty acids in the animal body. The finding of uncommonly high respiratory quotients (R.Q.'s) after glucose administration in rats with symmetrical hypothalamic lesions led to the discovery that similarly high R.Q.'s are exhibited by rats trained to eat their entire day's ration of food in a short time. Subsequent study of this phenomenon demonstrated the feasibility of investigating the conversion of carbohydrate to fatty acids in the rat by the technic of comparing the respiratory exchange of normal animals with that of "trained" ones. Finally, information gained from this method of studying fatty acid synthesis proved to be useful in an analysis of the mechanisms involved in the development of hypothalamic obesity, and of the metabolic repercussions of established obesity on the organism.

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The hypothalamus has been accepted by many investigators as an important center for the regulation of carbohydrate metabolism in the same way that medullary centers control respiration. Evidence for this point of view, however, is inconclusive and controversial (see Long"2) except for the well-confirmed transient hyperglycemia and glycosuria which follow hypothalamic stimulation or damage (Aschner,1 Himwich and Keller7). Houssay and Biasotti8' 9, 10 reported alleviation of pancreatic diabetes by lesions placed in the tuberal portion of the brain-stem of the toad. In the dog, however, similar lesions had no such effect. Amelioration of pancreatic diabetes was later descrilbed by Davis, Cleveland, and Ingram5 in cats with hypothalamic lesions. The mechanism of production of this effect was not specified, but it was assumed to have been due to interruption of the nerve supply or interference with the blood supply of the anterior lobe of the hypophysis. Their conclusions have been widely quoted in both experimental and clinical literature, but apparently their data have not been confirmed. The effect of experimental hypothalamic lesions upon carbohydrate metabolism has now been studied in albino rats prepared in one of three ways: (1) An attempt was made to confirm the results of Davis, Cleveland, and Ingram5 by producing bilateral hypothalamic lesions in rats which were frankly diabetic as the result of partial pancreatectomy. At the time of hypothalamic operation the glycosuria of each of the rats was quantitatively well stabilized; the effect of the operation, therefore, could easily be determined. (2) The well-known frequency of association of clinical obesity with diabetes mellitus led also to an attempt to study this association in the rat. Partially pancreatectomized rats which had no spontaneous glycosuria were subjected to hypothalamic lesions of the type which produces hyperphagia and obesity ((Brobeck et al.3). In this way it