A study was undertaken to clarify the mechanism by which the specific localization of the hypothalamic lesions takes place by injection of goldthioglucose (GTG) which causes the development of obesity in mice.
1. A new method for demonstration of the cerebral lesion caused by GTG, GTG-trypan blue double treatment, was established.
2. From the histological results obtained by above-mentioned method, and stained by hematoxylin and eosin and phosphotungustic acid hematoxylin, the severest lesion produced by GTG was in the nucleus arcuatus. Some changes, though variable in degree, were always recognized in the nucleus ventromedialis.
3. The results of trypan blue vital-staining and radioautography with I¹³¹ that the area of most increased permeability within the brain was the neighboring portion of the nucleus arcuatus.
4. There was a tendency that the incidence of development of obesity by GTG treatment was higher among younger mice.
5. The experiments with P³² showed a tendency that younger mice have the increased permeability within the brain.
On the basis of above-mentioned evidences, the following conclusion can be drown : there is entirely intimate correlation between the specific localization of hypothalamic lesion caused by GTG and the specificity of the hypothalamic blood brain barrier in mice.

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Pathophysiological studies were performed on the spontaneously obese mice (Sp obese mice), which were found among dd/S stock mice in the Animal Center in Kyoto University, and on the goldthioglucose-induced obese mice (GTG obese mice). The results of both obese mice were compared and the etiologies were discussed.
1. In GTG obese mice, there was a tendency of hyperphagia caused by the hypothalamic destruction.
2. In Sp obese mice, the existence of hereditary disposition was suggested. A hyperphagic tendency was not recognized in these mice.
3. GTG obese mice showed a temporal glucosuria for the first 2-3 days after GTG treatment. Though the glucosuria became negative soon, it appeared again when they have developed obesity. And some of GTG obese mice showed hyperglycemia. Sp obese mice showed in general a hyperglycemic tendency.
4. The hyperglycemia in both obese mice were not affected by growth hormone administration.
5. The insulin sensitivities in GTG and Sp obese mice were similar to that of control.
6. GTG obese mice showed lower temperature than the control mice. The lowered temperature and the degree of obesity were not parallel.
7. The heart, liver, spleen, testes were significantly heavier in both GTG and Sp obese mice than those of control mice. In Sp obese mice, the kidneys and adrenals were especially heavier than those of control and GTG obese mice. The increase of the heart weight was also prominent in Sp obese mice.
8. Among the basophilic cells in the pituitary of Sp obese mice, were scattered some vacuolated cells.
9. The histological picture of the thyroid of GTG obese mice suggests hypofunction, and that of Sp obese mice hyperfunction.
10. In Sp obese mice, the adrenal cortex was hypertrophied. 11. The pancreatic islets of Sp obese mice showed remarkable enlargement due to an increased number of β cells. Degeneration of β cells was found also in these obese animals.
12. Fatty liver was present in GTG obese mice but not in Sp obese mice. In Sp obese mice, fat emboli in the glomeruli were found. This finding suggests the existence of lipemia in these animals.
13. Sp obese mice showed a less amount of liver glycogen.
14. In histochemical studies of enzyme activities, GTG obese mice showed no significant changes.
On the other hand, Sp obese mice showed some abnormalities in activities and distributions of various enzymes. These were especially prominent in the liver. On the basis of above-mentioned findings, the etiologies of the development of obesity in GTG and Sp obese mice are supposed to be different. In GTG obese mice, the most important etiological factor is hyperphagia induced by the hypothalamic lesion. Several changes observed in these obese mice definitely suggest that they are secondary to the hypothalamic lesion or hyperphagia. On the other hand, in the case of Sp obese mice, the hereditary disposition, hypertrophies of the adrenal cortex and of the pancreatic islets and a less amount of liver glycogen are supposed to play important roles in developing obesity.

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The histological and enzyme histochemical findings of the adrenal cortex in the patient with carcinoma of the prostate and the breast were studied. Materials were obtained from 13 surgical and 5 autopsy cases of prostate carcinoma and 8 surgical and 8 autopsy cases of breast carcinoma. For the control study, the adrenal glands of 26 autopsy cases with bronchogenic carcinoma and of each autopsy and surgical case of miscellaneous diseases were used. Adrenocortical hyperplasia in 15 surgical and 1 autopsy cases with Cushing's syndrome and in 3 autopsy cases with adrenogenital syndrome were also examined. In addition to the routine histologic examinations, histochemistry for glucose-6-phosphate dehydrogenase and nine other dehydrogenase and oxydative enzymes was studied in the 4 surgical cases with carcinoma of the prostate and the breast, and in 7 control cases including hyperadrenocorticism.
Marked hyperplasia of the compact cell is usually diffuse and rarely nodular in the deeper cortical layers except for an occasional finding in cases with carcinoma of the prostate as the previous authors detected at autopsy and in surgical cases. The lesion was, however, regarded as the effect of orchiectomy and administration with estrogenous hormone. Medication with synthetic corticosteroids induced involution of the above diffuse hyperplasia of the deeper cortex, but the lesion of nodular hyperplasia remained uninvolved.
The cortical lesion was affected by adrenalectomy whether both adrenals were removed at the same time or at two separate times. In the gland secondarily removed at intervals of about three weeks, marked hyperplasia of the whole cortex was detected, while the lesion of the first one was less evident and usually limited in the deeper cortical layers.
Autopsy materials in cases with carcinoma of the breast had several fators inducing pleomorphism of the histology ; e.g. adrenal metastasis, ovariectomy, medication with carcinostatics and testosterone, and irradiation. In a surgical case with prologed medication with testosterone, the whole cortex reduced in width and coagulatation atrophy and necrosis of the cortical cells particularly in the inner layers were confirmed.
The fundamental findings were observed in the adrenals bilaterally removed at the same time from the patient with no castration and no hormone administration, two of prostate carcinoma and six of breast carcinoma. The inner cortical layers generally exhibited a slight hyperplasia even in cases without adrenal metastasis and the lesion was interpreted as the borderline between physiologic and pathologic changes by the examination of usual histologic stains. The lesions in cases with prostate carcinoma were generally more detectable compared with those in breast carcinoma. However, the difference of sex and age distribution between both groups should be taken into consideration for the interpretation of the above findings.
Significant findings were confirmed by the histochemical studies for oxydative enzymes in the untreated cases of both carcinoma groups, in comparison with those of adrenocortical hyperplasia in cases with Cushing's and adrenogenital syndromes and of other control cases. The distribution of histochemically detected activity of glucose-6-phosphate dehydrogenase and lactic dehydrogenase was increased in the deeper layers. The distribution of nonspecific esterase and acid phosphatase was distinctly increased in density and extended from the deeper layers of usual location to the outer cortical layers. The findings were comparable to those of congenital adrenocortical hyperplasia in the manner of distribution, and different from those in Cushing's cases.
It was considered that the lesions are not induced by the stimulation of carcinoma tissue, but exist as a somewhat abnormal course of physiological aging of the adrenal cortex, manifesting as the increase of the deeper layers by consuming of the fasciculata in the narrow meaning.

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It is well known that adrenal corticosteroids have many biological effects on the carbohydrate metabolism.
However, the mechanism of corticosteroids on carbohydrate metabolism has not been completely clarified and remains to be studied.
In the present investigation, it was intended to study the effects of dietary carbohydrates on the experimental steroid diabetes induced by Ingles method in which 10 mg of cortisone was administered to rats daily. Furthermore, the effect of anabolic steroid (Oxymetholone-HMD) on steroid diabetes was studied.
In this experiment, rats were divided into two groups, namely 1) rats fed with customary diet 2) rats forcedly fed with high carbohydrate diet. In the case of customary feeding, the rats were fed with 18.0 g of commerical diet (Oriental Co. LTD.) daily containing 9.47 g of carbohydrate, 0.99 g of fat and 4.36 g of protein. In the second group, they were forcedly fed by a gastric tube with the solution containing 17.08 g of carbohydrate, 2.76 g of fat and 5.94 g of protein.
During the experimental period, fasting blood sugar level, urinary glucose excretion and body weight were determined. The glucose tolerance test was performed using 10 cc of 20% glucose solution just before, one week and two weeks after cortisone administration.
The results of this experiment are summarized as follows :
1) In both customary and high carbohydrate diet groups, it was ascertained that the fasting blood sugar level increased late in the experimental period (10 to 14 days after cortisone administration). The rise of blood sugar level was slight in the customary diet group, but in the high carbohydrate diet group a marked rise in the blood sugar level was noticed.
The group fed with the high carbohydrate diet alone, showed a rise of fasting blood sugar level early in the experimental period (2 to 4 days) and then returned to normal late in the experimental period.
2) Urinary glucose was not shown in the customary diet group during the whole experimtal period in spite of the cortisone administration. In the group fed with high carbohydrate diet alone, urinary glucose was temporarily seen early in the experimental period. When cortisone was administered to the group fed with high carbohydrate diet, glucose excretion in the urine increased more remarkably late in the experimental period than in the rats fed with high cardohydrate diet alone.
3) The hyperglycemic effect of cortisone in the high carbohydrate diet group was inhibited completely by simultaneous administration with anabolic steroid. Urinary glucose excretion was inhibited also completely by simultaneous administration of two agents. In the high carbohydrate diet group treated with anabolic steroid, fasting blood sugar level decreased, but a little glucosuria was seen in some animals.
4) A remarkable dercrease in body weight was observed in both groups fed with high carbohydrate diet and customary diet after cortisone administration. However, the decrease in body weight was inhibited by the combined administration of anabolic steroid steroid and cortisone. On the other hand, the boy weight increased considerably in the high carbohydrate diet group after anabolic steroid administion.
5) The glucose tolerance of rats fed with the customary diet lowered considerably after administration of cortisone and in the animals administered with cortisone and anabolic steroid simultaneously, glucose tolerance lowered one week but returned to normal two weeks later.

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Experimental studies were carried out for the purpose of investigating an influence of the thyroid function on estrogen metabolism. Firstly, the urinary estrogen of the patients with thyroid diseases was determined, and Ittrich's chemical estimation with a certain modification method was employed.
Then, Estradiol was administered to the women who had been castrated, and also to the amenorrhoic women ; all had been previously administered with the thyroid substance or antithyroid agent. They were observed for their urinary excretory pattern. The drug was composed of estradiol undecenoate 10 mg. with estradiol benzoate 2 mg., and was injected intramuscularly at the same time.
Investigation was made on the relation of estrogen to the thyroid function of the patients who had known thyroid diseases. The following conclusions were obtained.
1. Total estrogen in the thyroid patients revealed a value within the normal range. No difference between the cases of hyperthyroid and hypothyroid was found.
2. However, Et/Eo+Ed value had decreased in relation with increased function of the thyroid.
3. Estriol fraction was reduced when T₃ administered to the amenorrhoic patients. 4. No urinary estrogen variation was seen when the thyroid substance or antithyroid agent was administered to the castrated women.
5. When Estradiol was administered to the euthyroid women, the excretory estrogen reached a peak on the 4th day.
6. It was found that the estrogen metabolism would become accelerated when Estradiol was administered to the women treated with T₄ beforehand, but an increase of estriol was less when compared with those of either estrone or estradiol. Therefore, it might be concluded that conversion of estrone to estriol is hindered.
7. With the antithyroid drug, it was found that estrogen metabolism became much slower.
8. Influence of the thyroid hormone on estrogen metabolism was found to be identical whether in castration or in amenorrhea.
9. The drug effect was observed in the cases in which estrogen value was higher when T₃ treatment was tried in the women who had amenorrrhea or anovulatory cycle regardless of thyroid function before treatment.

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