With a view of investigating the possibility of augmented or altered.mineralocorticoid activity in essential hypertension, the excretion of aldosterone in hypertensive patients was compared with that of normotensive subjects in various clinical and experimental conditions with simultaneous measurement of urinary electrolytes and of urinary total 17-OHCS.
A method for determination of urinary aldosterone was presented. A 24 hour sample of urine was acid-hydrolyzed and extracted with chloroform. After purification of the crude extract by benzene-water partition and column chromatography on florisil gel, the aldosterone was isolated by double chromatographic technique, first in Mattox's formamide-butyl acetate-water system, second in Bush B₅, system of benzene-methanol-water and measured by the blue tetrazolium reaction. The simplicity and specificity of the procedure was proved to be generally satisfactory for clinical use.
Under basal condition of dietary sodium intake of 290 mEq per day, the sodium excretion became lower along with the elevation of blood pressure. Some of the hypertensive patients seemed to have slightly increased excretion of aldosterone when compared with normotensive subjects. The difference, however, was of questionable statistical significance. Furthermore the values of urinary aldosterone had no correlation with their respective sodium output in urine. No differences in urinary potassium and 17-OHCS were observed between hypertensive patients and normotensive subjects.
Following an infusion of 500 ml of 4% sodium chloride, hypertensive patients responded with marked and persistent water diuresis and natriuresis than did normotensive subjects. The fall of aldosterone excretion was apparently limited in the hypertensive group. The response of urinary potassium and of urinary 17-OHCS was similar to that of normotensive subjects.
During the restriction of sodium intake of 25 rnEq per day, the patients with slight or moderate hypertension had enhanced sodium conservation capacity with more pronounced increase of aldosterone excretion. But the pattern of response to sodium restriction showed wide individual variation and the quantitative inverse relationship did not exist between sodium excreted in urine and urinary aldosterone level. In hypertensive patients in the advanced stage, these responses were rather impaired. The urinary potassium and 17-OHCS did not change consistently.
Although the definite hyperaldosteronism in essential hypertension could not be established, it may be plausible to say that there is some difference in the adaptive response of aldosterone excretion between normotensive and hypertensive subjects.

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Uncomfortable side-effects are often observed clinically in the cases of overdosed administration of estrogens as the functions of anterior pituitary were under the influences of estrogen.
The purpose of this article is, therefore, to study histochemical changes of the anterior lobe of the pituitary gland after administration of various kinds of estrogens.
Female, matured and non-parous rats and spayed rats were used as test-animals, and Estradiol benzoate, Estrone, Estrior, Ethinylestradiol, Hexron, Methallenestril and Chlorotrianisene of various con-centration were administered to the animals. Experimented histochemical methods are as follows ; cytol reaction (so called periodic acid-Schiff reaction), pyronin-methylgreen staining, Gomori's aldehyde-fuchsin staining, Gomori's alkaline phosphatase staining, Ohara's method for sulfhydryl and haematoxylin-eosin staining. Changes of weights of the pituitary, adrenal glands and ovaries were also followed.
It could be concluded from the obtained results that :
1) Continuous administration of estrogen of small doses stimulated the anterior pituitary function, while the large doses showed reverse effects.
2) Potency of estrogenic effects could be ranked : Estradiol=Ethinylestradiol>Hexron, Chlorotrianisene>Estrone>Vallestril.
3) Estriol which has been regarded as an estrogen-metabolite showed some mild stimulating effects on the anterior pituitary gland.
4) Notable changes were observed in the basophilic cells of the anterior pituitary gland after the administration of estrogens.
The PAS-positive substance in these cells might have certain relationships with the anterior pituitary function.

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The total catecholamine content of urine determined chemically by our modification of Euler and Floding's method.
1) The biochemical activity of catecholamine in stored urine was kept up by the addition to the urine of 6N sulfuric acid. This acid, which interferes with subsequent procedures when added in a relatively large amount, was added to the material in a quantity varying in proportion to the age of the child and not exceeding 10 ml.
2) Addition of EDTA (to the material) while catecholamine was being adsorbed to aluminum oxide in it, and washing with aceton under filtration and with chloroform of the material under filtration, facilitated the procedure of condensing and extraction the substance and prevented the appearance, during colorimetry, of a fluorescence from some other substance.
3) 0.1 ml of 0.25% Zinc sulfate used during fluorimetrical determination of Catecholamine contained in a material kept of pH 6.0 stabilized in intensity the fluorescence from the substance.
4) Catecholamine from urine, when preserved in our standard solution-adrenaline, mixed with 0.5 N-sulfuric acid in the ratio of 100 μg/ml and added with a small quantity of EDTA-, remained for a year or more without losing none of its potency.
5) The rate of Catecholamine which was recovered by our procedures was 60% ± 2%-rather low but so constant that 60% was taken as its standard recovery rate.

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As to the control of the thyroid by the hypothalamus, many workers now consider it as humoral regulation. In 1955, it was found out in our department that there is a tendency in the hypothalamus to stimulate selectively the hypophysis-thyroid system both functionally and morphologically, and since then studies have been performed by us on the central system governing the thyroid. As the consequence a substance was demonstrated, which was provisionally designated as thyrotryphin releasing factor. The author extracted TRF from urine, and made studies on its purification, and the following results were obtained.
(1) Crude TRF was precipitated by adding zinz sulfate and potassium ferrocyanide to urine, and extracted by using 97-80% ethanol as solvent. In this way, about 150 mg of TRF was harvested from 1000 ml of urine.
(2) In electrophoresis in veronal buffer (pH 8.5), crude TRF shifted toward the cathode, and in ion exchange resin, Dowes 50 × -2, it was separated in the acid portion. It showed maximum absorption of ultraviolet ray at 240 mμ and 280 mμ.
(3) The -7.8 and P₂ fraction were not protein nor lipoid. As to the development of color, it was positive only in ninhydrin and Sakaguchi reaction.
(4) The P₂ fraction always stimulated the hypophysis-thyroid system, activating it significantly both histologically and functionally.
(5) TRF was always contained in ninhydrin positive fraction, and one and two-dimensional paper chromatography and hydrolysis suggested that it would be peptide.

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A total of 10 Wistar rats, 5 females and 5 males, 90 days of age, were given intramuscular injections of methiocil in a daily dose of 7.5 mg/100 g for 3 days, and subsequently 10 mg/100 g for 32 days.
Examinations, morphological and physiological, on functions of the thyroid of the animals exposed to methiocil, revealed that the standard procedures of methiocil administration mentioned above could result in hypofunction of the thyroid.
Male and female Wistar rats treated with methiocil in the standard fashion were mated to obtain F1 animals (offspring).
These F1 animals, when 90 days old, were also treated with methiocil in the standard fashion, and were mated to obtain F₂ animals (Second generation offspring). F₃ and F₄ animals (successive generations) were obtained also by the same procedures.
Measurements of the body weight, serum PBI, total cholesterol and I¹³¹ uptake, and histological and histometrical studies on the thyroid gland and other endocrine organs were performed in 17, 14, 14, and 11 cases of the F₁, F₂ F₃ and F₄ animals, respectively, and in 37 cases of normal rats.
The results obtained illustrate that a progressively increasing hypofunction of the thyroid gland could be induced in offspring rats treated with methiocil for successive generations.

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Measurement of a total of 17-KS and its fractions excreted in the urine was made on the rabbits obtained from the diabetic parents by successive mating for seven or eight generations. Some of these rabbits were under the examination 50 to 365 days after an additional treatment with alloxan was employed. The following results were demonstrated, comparing with the data from control rabbits with or without alloxanization.
a) In the rabbits born from the sicked parents an increase in amount of 17-KS and II, III, VI, VII fractions were observed. The increase became more apparent with the successive mating generations and it was very marked in after the fourth generation in which spontaneous diabetes developed.
b) Amounts of 17-KS and its II, III, VI, VII fractions in the intact rabbits became under the normal levels when diabetes developed after administration of alloxan.
c) Amounts of 17-KS and its II, III, VI, VII fractions excreted in the urine in the rabbits born from the sicked parents up to the second generation showed a decrease after alloxan administration, which were larger than those excreted in the urine of the alloxanized control rabbits and which were smaller than those of normal rabbits. However, in the rabbits from the sicked parents from the third to the fifth generations of the successive mating, a decrease in amounts of 17-KS and its II, III, VI, VII fractions was resulted from alloxanization, remaining at the level above normal ranges.
Measurement of a total amounts of 17-KS and its fractions, FGS and uropepsin were made on the following animals (I) the first group, Wistar rats with spontaneous diabetes in both sexes born from the spontaneous diabetic parents, at definite intervals of time from the weanling age to approximately 120 days of age. (2) the second group, some of the male rats of the first group, exposed to alloxanization when the animals showed negative urine sugar. The following results were obtained, comparing with the data from normal rats with or without alloxanization.
a) In Wistar rats of the first group, larger amounts of 17-KS and its II, III, VI, VII fractions, FGS and uropepsin were excreted in the urine than those in the normal rats during a full course of maturation and aging since weanling age.
b) In normal rats with alloxanization, an increase in amount of the metabolites mentioned herein observed 10 days after the treatment was followed by a persistent decrease.
c) The male rats in the second group, alloxanization also resulted in a temporary increase in the urinary amounts, subsequently followed by a decrease, continuing for at least 3 months, amounts in the decreasing stages still being remained in over normal ranges.
The following conclusions may be obtained from the results mentioned above :
1) In the offspring rabbits and Wistar rats born from diabetic parents, the hyperfunction of the adrenal cortex can be observed, the degree of which being gradually more apparent with successive mating generations.
2) The hypofunction of the adrenal cortex can be developed in the animals when rabbits and Wistar rats were became diabetic by application of alloxan.
3) The offsprsng animals born from the diabetic parents, when alloxanization is employed, show various function states, from hyper- to hypo-function to less extent, corresponding to the generation number of the successive mating.

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