Adrenal Cortical Extract Research Articles

Remembrance: excerpta memorabilia.

Only because I had to stay up most of the night at the lab in Madison (tending to my adrenalectomized rats with my own adrenal cortical extract) did I become aware that Roy, with Eunice’s help, was trying to remove the pituitary from rats. Only P. E. Smith of Columbia was performing it successfully. Roy Hertz, after his B.S. in zoology at Madison, had gone to Columbia for his Master’s, but was unable to get to see Smith do the operation. Now Hertz was back at Madison for his doctorate and was working as Hisaw’s research assistant. trips to collect galls off oak trees for their entrapped wasp larvae. After many such nights, when Roy and Eunice knew why I was there, and I learned what they were doing, Eunice pledged me to secrecy. Roy did not want “the Boss” or others to learn that he was trying but might fail. However, he succeeded, with 30-day-old rats, parapharyngeal approach, a hand drill which a friend had made, and an oral suction tube (with a side “catch”). I have often wondered how many rat “pits” Ray may have swallowed! Some years later, however, the Women Students’ Organization petitioned President Wells to organize a course in Marriage and The Family. Our bachelor president said he would have to appoint a faculty committee to determine how this should be done and who would be involved. He asked for suggestions from the women students, and Kinsey was among those suggested. “But,” said Wells, *why Kinsey-he studies gall wasps!” Their answer was that as a biology teacher he had a reputation of giving straight, frank, and useful answers if personal questions were asked. By 1940 Kinsey had essentially stopped his gall wasp research and had been chairman of the faculty group giving the Marriage course for students over the age of 21 or with parental consent!!! I (R.L.K.) was one of the-lecturers in the From then on Roy was Hisaw’s “boy.” course.

Stimulation of HCO 3− excretion in frog skin by urinary and adrenal cortical extracts

1. 1. There is a substance extractable from human urine which stimulates frog skin to excrete bicarbonate. The response to this extract is delayed, taking 4–9 hr, depending upon the dosage. 2. 2. The amount of this substance varies with the bicarbonate intake of the urine donor. 3. 3. This is a reasonable dose-response curve to the extract. 4. 4. A substance with the same solubility characteristics, and which stimulates bicarbonate excretion with a similar time response is present in adrenal cortical extracts.

Cardiovascular failure in experimental adrenal insufficiency: a historical revival.

CARDIOVASCULAR FAILURE IN EXPERIMENTAL ADRENAL INSUFFICIENCY: A HISTORICAL REVIVAL R. A. CLEGHORN* The rapid advances in cardiovascular studies in the past 4 decades by themselves have inevitably left many earlier observations stranded like flotsam after a high tide. Perhaps an equal threat to historical continuity may have arisen from the current tendency toward computer search of the literature in which, not merely does much of science appear to have been performed within the last decade or decade and a half, but anything which is not appropriately indexed according to the computer is simply lost. A purpose in the present writing is the conviction that much of the past work, buried apparently beyond the reach of memory, may well have relevance if excavated from tbe dry sands ofjournals where it lies buried. On the chance that studies with which I and others were concerned in the thirties and early forties fall into this category, I have tried to rescue and bring together some of the material which might be of interest to current pundits for heuristic as well as historical reasons. My initial involvement with studies on failing circulation, which turned out to be the core ofthe adrenal insufficiency problem, had to do with physiological investigations concerning the respiratory quotient (R.Q.) and acid-base balance in eviscerated, decerebrate cats in 1930 [1, 2]. The objective was to establish the R.Q. of this muscle preparation. It proved to be about 0.8 prior to depletion of the alkali reserve and a breakdown in circulatory homeostasis. In the following 2 years, my efforts were occupied witb the methods which had just become available for preparing an extract of the adrenal cortex and demonstrating its efficacy by maintaining the life of adrenalectomized cats [3]. The aim The author is indebted to Prof. John Grayson, Department of Physiology, University of Toronto, for his helpful criticisms and suggestions. * Emeritus professor of psychiatry, McGiIl University; consultant, Department of Psychiatry, Sunnybrook Medical Centre, 2075 Bayview Avenue, Toronto, Ontario, Canada M4H 3M5.© 1983 by The University of Chicago. AU rights reserved. 0031-5982/84/2701-0357$01.00 Perspectives in Biology and Medicine, 27, 1 ¦ Autumn 1983 | 135 was to ascertain the nature of the life-maintaining functions of the adrenal gland which were not known then, though it seemed that death occurred with a decline in the circulation. Concurrent experiments on the influence ofautonomic nerve activity on carbohydrate metabolism in the Aberdeen University laboratory where I worked seemed pertinent. This study, which was reported by Donhoffer and Macleod [4], revealed a role for an adrenal cortex hormone in the autonomic nervous system control of glycogen and sugar release from the liver. Role of the Adrenal Gland ADRENALECTOMY IN THE FROG AND EFFECT OF ADRENAL CORTEX EXTRACTS As a means of investigating the possible relationship between the adrenal cortex and autonomic nervous system, I studied adrenalectomy in frogs, repeating the 1914 experiments of Loewi and Gettwert [5], first, while in the laboratory of the Department of Medicine at the Elizabeth University in Pecs, Hungary, in 1932, and then at the Wilhelmina Gasthuis in Amsterdam (unpublished observations). I found, as had Loewi and Gettwert, that frogs subject to cauterizing of the homologue of the adrenal cortical tissue that lay on the surface of the kidney died after a few days (3-8), showing a terminal bradycardia. At death the heart was in diastole and most of the blood seemed to be in the abdominal vessels at postmortem. Oedema of the peritoneal cavity was frequent due to kidney damage while cauterizing the adrenal tissue. In experiments in which electrical stimulation was applied from head to foot of the adrenalectomized frog, the bradycardia of the adrenal insufficient state appeared sooner. Atropine placed on the heart caused a temporary quickening, but cutting of the vagi had no apparent effect on the downhill course. This suggested that stimulation of the cardioaccelerator (ca.) nerves and their exbaustion was of greater importance than vagal excitation in the development of the bradycardia. In other experiments the isolated frog heart was studied using a Straub cannula perfused with Ringer's solution. It was found that the adrenal cortical extract had a positive inotropic and chronotropic effect...

Adrenal cortico-medullary transplant with antihypertensive activity in the rat.

THE suspicion that the adrenal gland may possess an antihypertensive function rests on the observation that adrenal cortical extracts have antihypertensive activity in man and oppose hypertension induced by deoxycorticosterone in the rat1,2. We have reasoned that if there is such a function, or a salt-losing role for the adrenal gland3, it is probably localized outside the zona glomerulosa. We have, therefore, carried out a series of transplantation experiments with potential autografts from the medulla and adjacent zona reticularis in the rat. Viable transplants have been produced and appear to have antihypertensive activity.

The Relationships Between Adrenal Cortical Steroids, Parathyroid Extract, and Calcitonin

The Relationships Between Adrenal Cortical Steroids, Parathyroid Extract, and Calcitonin

Urine Output, Saline Intake, and Adrenal Factors after Lethal Whole-Body or Intestinal Irradiation

Daily urine output and saline intake were measured up to 5 days after whole-body or intestinal x-irradiation (1460 R) of intact or adrenalectomized rats treated or not with adrenal cortical extract. Saline-drinking caused polydipsia, polyuria, and increased urinary chloride concentration in nonirradiated rats. Irradiation abolished saline-induced polydipsia, caused hypodipsia, and caused "water diuresis" with normal or subnormal urinary chloride concentration on the first day, especially after whole-body irradiation, then progressive oliguria. Adrenalectomy delayed the full development of saline-induced polyuria and polydipsia in nonirradiated rats, enhanced the hypodipsic effect of irradiation on the first day, and reduced the diuretic effect of irradiation on the first day. Treatment with adrenocortical extract partly counteracted the early depressing and later enhancing effects of adrenalectomy on the saline-induced polyuria and polydipsia in nonirradiated rats and had little or no consistent effects o...

Blood Cells and Chemistry of Young Chickens During Daily ACTH and Cortisol Administration

ADRENAL cortical extracts (ACE) and glucocorticoids, as well as ACTH (adrenocorticotropin), increase acid-ophilic granulocytes and cause relative lymphopenia and heterophilia in chickens (Shapiro and Schechtman, 1949; Newcomer, 1957; Wolford and Ringer, 1962). However, where Shapiro and Schechtman (1949) found that ACE caused leucopenia, others have found that ACTH and cortisone acetate produced significant leucocytosis (Newcomer, 1957; Glick, 1961). Glucocorticoids and ACTH also significantly increase the levels of cholesterol and corticosterone in the plasma of fowl (Stamler, 1952; Siegel and Siegel, 1966). Adrenal steroids produce a hypercalcemia in chickens (Urist and Deutsch, 1960), and osteoperosis, as found in mammals (Storey, 1961) was demonstrated in laying hens injected with cortisone. Cortisone acetate also inhibits chondrogenesis in the long bones of cockerels (Hublé, 1957). Although ACTH has been shown to lower serum calcium in rabbits (Natelson et al., 1965), its effect on the blood calcium of avian species is not clear.Previous work .

Steroids and blood brain barrier alterations in sodium acetrizoate injury.

Steroids )TEROIDS have been widely used to ameliorate the effects of various kinds of cerebral injury. In experimentally induced injury some investigators indicate that steroids are beneficial,^1-7while others believe them to be without protective value.^8-11In cats with lengthy exposure of the brain to air, Prados¹attributed protection against swelling, electroencephalographic alterations, and increased capillary permeability (trypan blue) to the administration of extracts of anterior pituitary or of adrenal cortex. Grenell²repeated the brain exposure experiments in a variety of species and concluded that adrenal cortical extracts prevented structural and functional changes in cerebral cortex. Blinderman et al³produced cerebral injury in dogs by the intracarotid injection of vegetable oil. Four of his eight animals treated with methylprednisolone sodium succinate (Solu-Medrol) developed no edema, two did develop it, and two showed equivocal results. The positive effects in the latter four could have been due

Diverting adrenal venous effluent through portal circulation in dogs.

IT HAS BEEN shown abundantly that the liver can reduce or alter the biological activity of certain steroid hormones. 1-6 Perfusion studies in vitro have shown that gonadal and adrenal steroid hormones are metabolized by the liver. 5,6 There are many clinical and experimental observations relating the adrenal cortex to hypertension. It has been demonstrated that bilateral adrenalectomy abolishes experimental renal hypertension 7,8 ; adequate replacement therapy with adrenal cortical extract or desoxycorticosterone after adrenalectomy may fully reestablish experimental renal hypertension, 9 hypertensive vascular disease may be produced in rats by the administration of desoxycorticosterone and by the administration of a crude suspension of anterior pituitary gland. 10 Although there have been a few attempts to create adrenal vein-portal vein shunts, 11-13 the technique has not been entirely satisfactory. Complete diversion of the venous effluent of the adrenal is difficult to achieve due to the great number of vascular connections of

CORTICOTROPIN IN TREATMENT OF OCULAR MYASTHENIA; A CONTROLLED CLINICAL TRIAL.

Although it has been more than 20 years since Moehlig first used adrenal cortical extracts in the treatment of a patient with myasthenia gravis and reported dramatic improvement 1 the usefulness of corticotropin (ACTH) and corticosteroids in the treatment of this disease remained unsettled. Osserman 2 described them as drugs to be used with extreme caution, and Schwab 3 considered them still of questionable value. Why is there not a clearer understanding of the efficacy of these agents? This is partly because of the vagaries of the disease, ranging from apparently spontaneous remissions to sometimes equally sudden relapses. It is partly because of enthusiasms, the enthusiasm of the patient with his fervor to respond to a new treatment and the enthusiasm of the physician with his eagerness to help his patient. And partly, emphasized by the vagaries and the enthusiasms, it is because of inadequate trials. Perusal of the published

Effect of Steroids on Experimental Cerebral Infarction

Adrenal steroids have been used to treat cerebral edema ever since Prados et al 1 observed that spraying the cerebral cortex with adrenal cortical extract minimized the trypan blue staining which exposure otherwise induced. Pretreatment with cortisone also prevents edema formation around cerebral stab wounds, 2 and corticosteroids appear to reduce the edema that surrounds human and experimental brain tumors. 3,4 Whether corticosteroids reduce the cerebral edema and improve the clinical course of patients with ischemic cerebral infarction is unknown. Clinical statements have been made both pro 5,6 and con, 7 but there have been no controlled experimental studies on the problem. In the present work the glucocorticoid, dexamethasone, was given to rats both before and after a controlled anoxic-ischemic insult. The mortality and tissue changes were compared in treated and untreated animals. Method Adult male Sprague-Dawley white rats weighing 325-425 gm were used. As described in the previous paper

Whole body x-irradiation, nitrogen excretion and the adrenal gland.

Urinary nitrogen excretion by the rat increases after whole body x-irradiation. This response to irradiation is suppressed by adrenalectomy and can be restored by treatment of the x-irradiated adrenalectomized rats with adrenal cortical extract. The weights of the thymus and the spleen are decreased and the weight of the liver is increased in the rat following whole body x-irradiation; adrenalectomy produces only quantitative changes in these responses without affecting the direction of the changes. Blood amino acid levels are not affected appreciably by x-irradiation. From these facts it appears that nitrogenous materials other than amino acids or simple polypeptides are transferred from certain body tissues to the liver after irradiation. In the normal irradiated animal these nitrogenous materials are converted in the liver to glycogen, and the excess nitrogen appears in the urine. In the adrenalectomized irradiated animal the liver is unable to carry out this conversion. Treatment of the adrenalectomiz...

THE ACUTE EFFECTS OF INFUSED ADRENAL STEROIDS ON RENAL FUNCTION IN ADRENALECTOMIZED DOGS

ABSTRACT Infusions of cortisol (11β,17,21-trihydroxy-pregn-4-ene-3,20-dione), prednisolone (11β,17,21-trihydroxy-pregna-1,4-diene-3,20-dione), aldosterone (11β,21-dihydroxy-3,20-dione-pregn-4-en-18-al), and adrenal cortical extract have been given to four adrenalectomized dogs. The changes of inulin, creatinine, para-aminohippuric acid clearances, urine volume, and sodium and potassium excretion have been measured. Between experiments oral replacement therapy was given to obviate the effect of slow absorption of previously injected steroids. The effects of steroid-free control infusions have been studied. Varying the rate of infusion from 1.0–2.6 ml/min, and sodium from 0–170 μeq/min has little effect on glomerular filtration rates (G. F. R.). Infusions of cortisol (1.5 and 10 mg/h), prednisolone (2 mg/h) and adrenal cortical extract (10 ml/h) raised the G. F. R. and lowered the filtration fraction. As the G. F. R. increased the ratio creatinine: inulin clearance fell. The different dogs varied in their responses. Infusions of prednisolone and cortisol (1.5 mg/h) usually increased sodium output as G. F. R. rose. With aldosterone, adrenal cortical extract and cortisol (10 mg/h) there was sodium retention in three of the four dogs, the fourth was resistant to the sodium retaining action of these steroids while the plasma level was high. All steroid infusions increased potassium excretion. Cortisol increased free water clearance independent of G. F. R. provided the infusion rate exceeded 2 ml/min, prednisolone increased both osmolar and free water clearance, aldosterone increased osmolar clearance and reduced free water clearance.

Effects of thyroid and adrenal cortical hormones on restoration of liver protein and enzyme activity after partial hepatectomy in rats.

Propylthiouracil depressed and thyroxine elevated the succinoxidase activity of rat liver after 4 days of regeneration. Protein-depleted animals had a significant decrease in activity of succinic dehydrogenase and cytochrome oxidase, rate of restoration of liver mass, enzyme activity and new protein. Thyroxine increased the rate of regeneration and the enzyme activity even in protein-depleted animals. Adrenalectomized rats on low protein intake had a very low rate of regeneration and protein replacement and low amounts of new enzyme activity and new protein after partial hepatectomy. Increasing the dietary protein to 36% increased all of these factors significantly, but administration of cortisone or adrenal cortical extract, had little effect on enzyme activity even though its effect on protein restoration was about as good as that of the high protein intake. Apparently under certain conditions, these hormones can produce changes in specific enzyme proteins that are independent of changes in total cell protein.

The Effect of Cortisone Acetate on the Leukocytes of Young Chickens

ABSTRACT IT IS known that the adrenocorticotropic hormone (ACTH) and several adrenal steroids will decrease the number of circulating lymphocytes and eosinophils in certain mammals, Dougherty and White (1944) and Dougherty and Dougherty (1953). Less is known about the effects of ACTH and adrenal steroids on the circulating white cells in the chicken. Adrenocorticotrophic hormone has been reported by Huble (1955) to decrease lymphocytes and increase the number of heterophils, and to have no effect on lymphocytes and eosinophils, Stamler et al. (1950). Shapiro and Schechtman (1949) reported that the injection of adrenal cortical extract into adult chickens produced a transient lymphopenia and an increase in heterophils. The data of Huble (1955) and Bannister (1951) indicate that daily administration of cortisone acetate will reduce the lymphocytes and eosinophils and increase the number of heterophils in the chicken. The number of leukocytes and variation in differential counts after cortisone injection may not . . .

Stress Resistance in Thymectomized Rats

A method for determining stress resistance is employed for the investigation of a possible difference between thymectomized and normal animals with respect to their abilities to withstand the stressing effects of various nonspecific stressor agents. Rats are used as the test animals, and the experimental data evaluated by the Litch-field-Wilcoxon method. Evidence is provided to indicate that there is no significant difference in the ability of normal and thymectomized groups to withstand the stressing effects of dry heat, reserpine, and histamine. The restoration of normal stress resistance in thymectomized, adrenalectomized animals receiving adrenal cortical extracts is not dependent upon the process of thymus involution.

Influence of cortisone on the basophil granulocytes and the total white cell count in rabbit blood.

Several investigators (Ehrich, 1953; Asboe-Hansen & Kaalund-Jørgensen, 1956: and Boseila, 1958) have suggested that the basophil leucocyte and the tissue mast cell have some functional relationship in addition to their morphological similarities. Systemic cortisone administration results in a reduction of the number of the tissue mast cells, as well as degranulation or conglomeration of their granules (Asboe-Hansen, 1950; 1952; Videbæk et al., 1950); and oral cortisone administration induces a fall in the absolute count of circulating basophil leucocytes in man (Code et al., 1954). Injected subcutaneously, cortisone brings about a marked decrease in the total leucocyte count in rats (Hamilton, 1957). A single injection of adrenal cortical extract, corticosterone or cortisol produced lymphopenia in rabbits within few hours (Dougherty & White, 1944). In rabbits, as in rats, the lymphocyte is the predominant circulating white cell, and hence a total leucopenia might be expected along with the lymphopenia. The present investigation

Effect of x-ray irradiation on muscle fatigue in rats.

With the Ingle fatigue test, it has been demonstrated that a loss of muscle responsiveness, increased fatigability and decreased work output follow acute whole body irradiation. These effects increase with time postirradiation. In both normal and irradiated animals, strain differences were observed. In the dosage used, the administration of adrenal cortical extract did not improve performance. Adrenalectomy plus cortical extract did not improve performance. It has been postulated that the poor performance of the irradiated animals is related to a lack of glycogenolysis, poor intestinal absorption of glucose and circulatory collapse.

An experimental study of postoperative tumor metastases. II. Effects of anesthesia, operation, and cortisone administration on growth of pulmonary metastases.

CancerVolume 11, Issue 3 p. 460-462 ArticleFree Access An experimental study of postoperative tumor metastases. II. Effects of anesthesia, operation, and cortisone administration on growth of pulmonary metastases William E. Schatten M.D., William E. Schatten M.D. Surgery Branch of the National Cancer Institute, of the National Institutes of Health, Public Health Service, Bethesda, Md.Search for more papers by this authorWilliam M. Kramer M.D., William M. Kramer M.D. Surgery Branch of the National Cancer Institute, of the National Institutes of Health, Public Health Service, Bethesda, Md.Search for more papers by this author William E. Schatten M.D., William E. Schatten M.D. Surgery Branch of the National Cancer Institute, of the National Institutes of Health, Public Health Service, Bethesda, Md.Search for more papers by this authorWilliam M. Kramer M.D., William M. Kramer M.D. Surgery Branch of the National Cancer Institute, of the National Institutes of Health, Public Health Service, Bethesda, Md.Search for more papers by this author First published: May/June 1958 https://doi.org/10.1002/1097-0142(195805/06)11:3<460::AID-CNCR2820110304>3.0.CO;2-ECitations: 28AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. References 1 Agosin, M.; Christen, R.; Badinez, O.; Gasic, G.; Neghme, A.; Pizarro, O., and Jarpa, A.: Cortisoneinduced metastases of adenocarcinoma in mice. Proc. Soc. Exper. Biol. & Med. 80: 128– 131, 1952. 2 Baserga, R., and Shubik, P.: Action of cortisone on transplanted and induced tumors in mice. Cancer Research 14: 12– 16, 1954. 3 Baserga, R., and Shubik, P.: Action of cortisone on disseminated tumor cells after removal of primary growth. Science 121: 100– 101, 1955. 4 Diller, I. C.; Beck, L. V., and Blauch, B.: Effect of adrenal cortical extract on growth of certain mouse tumors. Cancer Research 8: 581– 589, 1948. 5 Eck, R. V.: Personal communication. 6 Engell, H. C.: Cancer cells in circulating blood; clinical study on occurrence of cancer cells in peripheral blood and in venous blood draining tumour area at operation. Acta chir. Scandinav. suppl. 201: 9– 70, 1955. 7 Fisher, E. R., and Turnbull, R. B. JR.,: Cytologic demonstration and significance of tumor cells in mesenteric venous blood in patients with colorectal carcinoma. Surg., Gynec. & Obst. 100: 102– 108, 1955. 8 Gaylord, H. R., and Simpson, B. T.: Effect of certain anesthetics and loss of blood upon growth of transplanted mouse cancer. J. Cancer Research 1: 379– 382, 1916. 9 Gottschalk, R. G., and Grollman, A.: Action of cortisone and ACTH on transplanted mouse tumors. Cancer Research 12: 651– 653, 1952. 10 Iwasaki, T.: Histological and experimental observations on destruction of tumour cells in blood vessels. J. Path. & Bact. 20: 85– 105, 1915. 11 Jude, J. R., and Schatten, W. E.: Effect of zymosan on heterotransplantation of tumors to rats. Cancer Research. In press. 12 Pomeroy, T. C.: Studies on mechanism of cortisone-induced metastases of transplantable mouse tumors. Cancer Research 14: 201– 204, 1954. 13 Pool, E. H., and Dunlop, G. R.: Cancer cells in blood stream. Am. J. Cancer 21: 99– 102, 1934. 14 Schatten, W. E.: Experimental study of postoperative tumor metastases; I, growth of pulmonary metastases following total removal of primary leg tumor. Cancer 11: 455– 459, 1958. 15 Snell, G. D.: Cytosieve permitting sterile preparation of suspensions of tumor cells for transplantation. J. Nat. Cancer Inst. 13: 1511– 1515, 1953. 16 Tadenuma, K., and Okonogi, S.: Experimentelle Untersuchungen über Metastasen bei Máusecarcinom. Ztschr. f. Krebsforsch. 21: 168– 172, 1924. 17 Warren, S., and Gates, O.: Fate of intravenously injected tumor cells. Am. J. Cancer 27: 485– 492, 1936. 18 Watanabe, S.: Metastasizability of tumor cells. Cancer 7: 215– 223, 1954. 19 Wood, J. S., JR.; Holyoke, E. D., and Yardley, J. H.: Experimental study of influence of adrenal steroids, growth hormone, and anticoagulants on pulmonary metastasis formation in mice. Proc. Am. A. Cancer Research 2: 157– 158, 1956. 20 Zeidman, I.; McCutcheon, M., and Coman, D. R.: Factors affecting number of tumor metastases; experiments with transplantable mouse tumor. Cancer Research 10: 357– 359, 1950. Citing Literature Volume11, Issue3May/June 1958Pages 460-462 ReferencesRelatedInformation

Pathologic changes in adrenalectomized and non-adrenalectomized rats exposed to cold.

Sexually mature male rats of the Sprague-Dawley strain were sensitized by removal of one kidney and feeding a diet containing 4 per cent sodium chloride. Adrenalectomized rats were treated with 4 cc. of aqueous adrenal cortical extract per rat per day. Groups of adrenalectomized and non-adrenalectomized rats were each subdivided into groups which were adapted to low temperature and kept at 3–5# for 60 days, and similar groups kept at room temperature forthe same period of time. An additional group of non-adrenalectomized sensitized rats were adapted to the overfeeding of the high salt diet by stomach tube. The amount of fluid diet represented approximately as much dry diet as was eaten ad libitum by the cold-exposed rats. The following pointswere established: 1. The rats exposed to cold ate much more food but gained less weight than did rats kept at room temperature. The rats which were overfed at room temperature became overweight.