Sixty-eight Wister-strain female rats, weighing around 70-80 grams, were used in the present experiment. (a) Both Skelton's adrenal regeneration hypertensive rats and Selye's DCA hypertensive rats were induced diabetic using alloxan 9 weeks after the first procedure to develop hypertension. (b) Alloxan diabetic rats were followed 9 weeks later by the Skelton's or Selye's procedures to develop hypertension. (c) Four groups of other experiments as illustrated in (6) were carried out. Measurement of the blood pressure was made in an interval of 7 days on all cases. All the rats were sacrificed 6 months later and were examined histo-pathologically. The following results were obtained.
(1) Skelton's adrenal hypertensive rats, when they were alloxanized 9 weeks later, showed rapid, but temporal decline of the blood pressure and then showed its gradual elevation. The systolic blood pressure at the end of the experiment was 183±6 mmHg in average of 6 cases ; this value being 67 mmHg or 30 mmHg higher than that of normal rats (116±13 mmHg in average of 5 cases) or the adrenal regeneration hypertensive rats (153±7 mmHg in average of 6 cases). Various lesions, such as hypertrophy of the heart, sclerotic lesion of the kidney, thickness of the arterial walls of the heart, kidney, spleen and pancreas, and periarteritis nodosa of the mesenteric artery were more marked in this group of rats than in the Skelton's hypertensive rats.
(2) Alloxan diabetic rats, were hypertensive by the technique of Skelton's adrenal regeneration 9 weeks later, showed marked and straight elevation of the blood pressure, having no tendency to decline. The systolic pressure was 214±11 mmHg in average of 6 rats at the end of the experiment. This value was 98 mmHg, 61 mmHg higher than that of normal rats, adrenal regeneration hypertensive rats respectively. Furthermore, the average blood pressure of this group was 31 mmHg higher than that of hypertensive rats followed with a alloxan diabetes. Hypertrophy of the heart, necrosis and scar formation in the heart muscle, sclerotic lesions in the kidney, thickness of the arterial walls in the heart, kidney, pancreas, and spleen, and periarteritis nodosa in the mesenteric artery were the most intensive in this group.
(3) When DCA hypertensive rats were followed with alloxan diabetes, temporal decline of the blood pressure was observed and gradual elevation of the pressure was followed without signs of decline. The systolic pressure at the end of the experiment was 180±7 mmHg in average of 6 rats, being 20 mmHg higher than that of DCA hypertensive rats (159±5 mmHg in average of 3 rats). Marked hypertrophy of the heart and other lesions in the heart, kidney and spleen and blood vessels were observed, paralleling the degree of the elevation of the blood pressure.
(4) Alloxan diabetic rats, when they were induced DCA hypertensive 9 weeks later, showed elevation of the blood pressure without a tendency of decline. The systolic pressure was 207±7 mmHg in average of 6 rats at the end of the experiment. This value was 91 mmHg, 44 mmHg, 27 mmHg higher than that of normal rats, DCA hypertensive rats, or DCA hypertensive rats followed with alloxanization, respectively. The lesions in the heart, kidney and blood vessels were the most intensive in this group of rats.
(5) In rats involved by both diabetes and hypertension, preceded by diabetes, lesions similar to human diabetic glomerulosclerosis were observed frequently (9 out of 12 cases). It was also noted that adrenal regeneration hypertension caused its development with greater frequency and in a larger extent (6 out of 6) than DCA hypertension (3 out of 6).
(6) No definite symptoms of hypertension were seen in the following four groups of rats :
1. rats with alloxan diabetes only,
2. rats administered with 1% saline solution with or without alloxan diabetes,

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Wistar male rats were subjected to induction of diabetes by application of alloxan and were mated with normal Wistar females to obtain their offsprings. The following three groups of the males with diabetes were used as male parents in the present report. 1) males having glycosuria for 14, 21, 22, 23, 24, 26, 27 or over 40 days. 2) males without glycosuria by insulin treatment of various length of time after over a month diabetization. 3) males with glycosuria for 23 days, during which time a period of aglycosuria for 3 days was inserted by insulin treatment at various stages. The off-springs thus obtained, weighing more than 150 gramms at the 90th day after birth, were killed and histometrical examination was done on the Langerhans' islets. The following results (1) - (5) were obtained, comparing with the similar examination of normal rats.
(1) In 14 cases of normal rats (7 males, 7 females) number of cr-cells were 14.8-20.1 (17.6±1.4 in average), number of β-cells were 65.4-67.2 (66.4±0.7 in average), area of a-cells were 58.3-69.4μ² (63.0±3.2μ² in average), area of β-cells were 103.4-119.4μ² (112.2±4.1μ² in average) and area of islets were 130.6-144.3 × 100μ² (138.0±3.6 × 100μ² in average).
(2) In 14 offsprings from the males with diabetic state of more than 40 days' duration, number of α-cells were 14.6-19.2 (17.2 ±1.6 in average), number of 8-cells were 57.8-59.4 (58.6±0.6 in average), area of a-cells were 54.2-61.3μ² (58.2±1.8μ² in average), area of β-cells were 105.3-111.3μ² (108.1 ± 1.6μ² in average) and area of islets were 114.8-132.0 x 100μ² (125.4±5.5 x 100μ² in average). Therefore, an evident disturbance was obserbed on the development of the β-cells.
(3) Four, 7, 6, offsprings, making a total of 17, from the males whose diabetes continued for 14, 21, 22 days, respectively, did not show any disturbance in the β-cell development and they were quite identical with normal rats. On the contrary, in all cases from the males whose diabetes was continued for 27 days, the disturbance in the 8-cell development was observed in an equal degree as in the cases from the males whose diabetes continued for more than 40 days. However, the duration of illness for 23, 24 or 26 days resulted in the disturbance in 6, 5, 3 cases (total of 14) among 10, 7, 6 cases, respectively, but no disturbance was observed in the remaining 4, 2, 3 cases (total of 9), having the same histometrical pictures as normal rats.
(4) The disturbance in the β-cell development was noted also in all of five offsprings from the males in which a period of aglycosuria for 3 days was inserted by insulin treatment after diabetization of a long period of time. Periods of aglycosuria for 7, 10, 14, 17, 21 or 27 days prevented the disturbance in the 8-cell development in 5, 5, 4, 5, 5 or 4 offsprings, respectively. Three groups of the offsprings 6, 3, 6 (a total of 15 rats) whose male parents had periods of aglycosuria for 4, 5, 6 days respectively were studied. It was of interest to note that some showed the disturbance in the 8-cell development and some didn't, the number of the former offsprings was 4, 1, 3 (a total of 8) and the number of the latter 2, 2, 3 (a total of 7).
(5) All 12 offsprings from the males whose diabetes was maintained for 23 days, during which time having a period of aglycosuria for 3 days from the 1st or the 12th day after occurrence of diabetes, did not show any disturbance in the β-cell development. A period of aglycosuria for 3 days at the other stages of the illness was responsible for the incidence of the disturbance in the offsprings in some instances.

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Urinary aldosterone output in 44 cases of various hypertensive patients was estimated by a modification of Nowaczynski's method. The results showed that urinary aldosterone output was related proportionally to the grade of the occular fundi, the blood pressure and the duration of hypertension, and was not followed by reciprocal changes in urinary sodium and potassium excretion regularly, but was quite regularly in extracellular fluid volume.
In the light of all findings described above, it seems to be proved beyond any doubt that the aldosterone secretion increased with the developement of arterial hypertnsion. This increased aldosterone secretion would be the main factor leading to an increased peripheral resistance and vascular reactivity of the arteriolar walls, accompanied with the expanded extracellular fluid volume and the changes of intra- and extracellular electrolytes. It is suggestive that the grade of arterial hypertension may become worse gradually by these changes.

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It has been known that Estradiol (wich will be abbreviated as ED hereafter) is, chiefly, in the liver metabolized to Estrone (which will be hereafter abbreviated as EO), and to Estriol (which will be abbreviated as ET hereafter). It has also been assumed that both EO and ET were, merely, metabolites or final products of the process and that estrogenic effect was lower in the order of ED, EO and ET. For the purpose of to detect this non-specific effect of these Estrogens (which will be abbreviated as E. hereafter), Author has administered E to immature and mature spayed femal rats and has studied the effect on the weights of the uterus, adrenals, hypophysis and ovaries. These estragen compounds were given with or without mixing each others.
The results are concluded as follows ;
(1) Author has administered ED, EO and ET to rats without mixing each others and studied the weight gain of the uterus. Their effects were stronger in order of ED, EO and ET, but in the cases of administration of large doses of these estrogen compounds, there were no differences in gaining uterine weight. In the other words, irrespective of the doses of the estrogen compounds as are stated above, gain in uterine weight approach to certain limiting values.
(2) The increase in weight of adrenals of the immature rats were more pronounced after they were administered ET compared with those after the administration of ED or EO. Also the weight gain of the hypophysis of the immature rats after administration of ET was observed. While the hypophysial weights were reduced after administration of large doses of EO and ED, they were, however, increased after administration of ET.
(3) The effect on the uterine weight gain was more pronounced with the mixture of EO, ED and ET compared with single administration of ED. On the other hand, the mixtures appeared to prohibit the effect of ED in the range of 0.001 mg. to 1.0 mg. for the uterine weights gain of the mature spayed rats, at dosage of 1.0 mg for adrenal weights gain of mature spayed rats and at the dosage of 0.001 mg. for weights gain or immature rats' uterus.
Author has shown that ED was the strongest estrogenic compounds and that, after ED has been metabolized to EO and ET, these metabolites might work as prohibiting agents against the effect of ED and also that they were not mere products of metabolism to be excreted for nothing. Author has also brought up the hypothesis that ET might have some stimulating effect on the hypophysis.

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The determination method of urinary aldosterone by Hernando-Thorn, based on the Neher-Wettstein's method, was improved in such points as acidhydrolysis, extraction with Cohen type continuous extractor and colorimetry as standard of dl-aldosterone.
The results obtained were as follows :
1) As 20 μg of dl-aldosterone free was added to urine of two normal adults persons respectively, the recovery of aldosterone by this method was 54.0% and 50.6%.
2) The urinary aldosterone determined on ten healthy adult persons, six males and four females, was between 2.0 and 12.0 μg per day, averaging 5.8±3.5 pg per day.
3) ACTH-Z of 20 units was intramuscularly administered for three consective days to four healthy adult persons, three males and a female, respectively, and then daily urinary aldosterone was measured in each case for three days before, during and immediately after the administration respectively.
But, no increased urinary aldosterone excretion was confirmed in any case after ACTH-Z injection.

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1) A male patients of typical primary aldosteronism, who was operated to demonstrate adrenocortical adenoma of left side, was measured urinary aldosterone sixteen times in the course of time by using the improved Neher-Wettstein's method as mentioned before, and increased urinary aldosterone output was found.
But soon after salt in diet was restricted, the urinary aldosterone happened to decrease was improvement of both the electrolyte metabolism and clinical manifestations.
This patient was administered ACTH-Gel intramuscularly every day for the periods of 4 days, but no altering effect on urinary aldosterone excretion was found.
2) Eight cases of non-familiar periodic paralysis, which is often encountered in male adults in Japan, were determined daily urinary output of aldosterone. In six out of eight cases, daily urinary aldosterone was determined and compared, not only in the period of attack, induced spontaneously or by provocation test, but also in the interval period respectively.
In all four case, which happened to appear typical paralysis, a marked increase of urinary aldosterone output was found during the attack, but in all the cases, in which only in complete attack was induced by provocation, the increase of urinary aldosterone was almost not observed.
Hyperthyroidism was noticed in many out of cases of periodic paralysis mentioned above, and paralytic attack happened to disappear in accordance with healing or improvement of hyperthyroidism after treatment with radioactive iodine (I¹³¹) or mercazole. In a case of periodic paralysis, in which paralytic attack disappeared after treatment with I¹³¹, provocation did not induce any attack and not increase urinary output of aldosterone.
From the above mentioned results, it may be concluded that adrenocortical hormones, especially aldosterone play an important role in the pathogenesis of paralytic attack in periodic paralysis, by influencing the metabolism of electrolytes.
3) In both two cases of liver cirrhosis associated with ascites and two cases of liver swelling caused by liver cancer and Hodgkin's disease respectively, the urinary aldosterone was markedly increased, and it was slightly increased in each two cases of liver cirrhosis without ascites, hepatitis and cholelithiasis, respectively.
4) In two out of four cases of essential hypertension was found that urinary aldosterone was slightly increased.

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Urinary aldosterone was measured, using the modified Neher-Wettstein's method as previously descrived, on twenty cases of various endocrine disorders.
The results obtained were as follows :
1) In four cases of Addison's disease determined, the urinary aldosterone showed a decrease or a tendency to decrease. And in the severe cases of Addison's disease associated with a markedly decreased Na/K ratio of serum, is was found that urinary aldosterone was remarkably decreased.
2) Out of three cases of Cushing's syndrome, urinary aldosterone was revealed to be almost normal in one cases, in which it was determined 2 times, and was to be slightly increased in the other one.
However, in the remaining one case, presumably combined with primary aldosteronism, urinary aldosterone was determined three times to be always markedly increased.
3) In all two cases of adrenogenital syndrome, urinary aldosterone remained normal.
4) Normal urinary aldosterone was found in one case of pheochromocytoma.
5) In three out of four cases of panhypopituitarism, urinary aldosterone indicated a tendency to silghtly decrease, but their values remained in normal range. In the remaining one case, in which autopsy demonstrated parenchymatous atrophy of the diencephalon due to the extensive infiltration of pinealoma, decreased urinary aldosterone was confirmed.
6) In all two cases pituitary dwarfism, urinary aldosterone was revealed to be around the lower limit of normal value.
7) Urinary aldosterone was found to be normal in one case of achromegaly.
8) In each one case of hyperthyroidism and myxedema, urinary aldosterone remained near the lower limit of normal value.
9) In one case of eunuchoidism, urinary aldosterone revealed to be near the upper limit of normal value.
10) From the results mentioned above, it may be conclued that aldosterone secretion is probably controlled by neither the hypophysis nor the other endocrine glands, but is considered to be directly controlled by the diencephalon.
However, further studies, concerning th is problem are needed.

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Polarographic measurements of endogenous Zn were made with soluble and insoluble fractions of several endocrine organs (pituitary gland, thyroid gland, parotid gland, submaxillary gland, thymus, pancreas, seminal vesicle and blood) of the male albino rats in normal and experimental conditions, in the latter of which animals were adrenalectomized and/or injected with DOCA or cortisone acetate.
1. Injection of DOCA or cortisone into nomal rats did not change in the contents of Zn in the most of the organs, with two exceptions, one of which is significant decrease in Zn content in both of soluble and insoluble fractions obtained from the pancreas, and the other increase in Zn content in the testis.
2. Zn contents in the most of the organs of the adrenalectomized rats showed a tendency to increase, which was recovered by injections with DOCA or cortisone. In pancreas, however, adrenalectomy together with the injections of the hormones showed significant decrease in the Zn contents.
3. Increase of Zn contents in soluble and insoluble fractions induced by adrenalectomy was restored more efficiently by DOCA than by cortisone.

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Distributions of Zn⁶⁵ injected intramuscularly were investigated with several organs (pituitary gland, thyroid gland, thymus, parotid gland, submaxillary gland, pancreas, testis, seminal vesicle, prostate, kidney, muscle and blood) of normal-, adrenalectomized-, adrenalectomized plus injected with DOCA or cortisone-rats, using r-counting well type scintillation counters.
1. Most of the tissues were shown to be highest in the specific activities at seven hours or 2 days after the injection of Zn⁶⁵ in normal rats. Adrenalectomy was responded by delayed Zn⁶⁵ uptake to and/or excretion from the tissues investigated. Effect of adrenalectomy on the uptake and excretion of exogenous Zn⁶⁵ was restored by injection with DOCA or cortisone, the former of which was more effective to the ability of the restoration than the latter.2. Distribution of exogenous Zn⁶⁵ in soluble fractions of the homogenized tissues was measured with the following results : Percentages of Zn⁶⁵ in soluble and insoluble fractions of each organ to sum of the activities of the the both fractions were not appreciably changed by adrenalectomy or injections of the hormones used in the present study. Larger amount of the activity in the soluble fraction than in the insoluble fraction was found in pituitary gland, thyroid gland, pancreas, spleen, liver and kidney, especially in the pancreas, and vice versa in seminal vesicle, prostate and muscle. In other organs, parotid gland, submaxillary gland and thymus, the activity was nearly equally divided into soluble and insoluble fractions.
3. Functional interrelationships between Zn⁶⁵ and endocrine organs were discussed in relation to the physiological significance of endogenous Zn.

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Pigment epithelium of the retina, embryologically, belongs to the nervous system, and its role in the visual function is exstremely important.
Using the retina of chick embryo, tissue culture experiments were performed by single cover slip method or by roller test tubes, and the growing process of pigment epithelium is measured by planometric means. Observations of cytological components of the growing cells were made by histochemical technics or with the aid of phase contrast microscope.
On the course of the experiments, several types of hormones were supplied to the nutritional media so that the influence of each hormone on the growth of the epithelium, especially of the pigment granules therein, might be examined.
The findings of the present experiments are as follows.
Chapter I
(1) Submitted to the tests are the pigment-epithelia of the retina extracted from chick embryo of between 8 and 11 days' incubation, that has proved to produce good results through preliminaly experiments.
The epithelia cultured by single cover slip method grow, by 96 hours, about 8.5 to 9.7 times in space.
By roller test tubes, there is one case the epithelium grow 8.74 times, until it stopped to grow after 168 hours.
(2) The pigment epithelia of the retina grow rapidly after the incubation period of 24 hours, forming a typical epithelial sheeth. (3) The distribution of the pigment granules and the protoplasmic granules of the pigment epithelium usually accords with the R.N.A. distribution which becomes apparent through the staining treatment for nucleic acid.
They occupy a fixed position in protoplasm paralleled with the direction of cell-multiplexing.
(4) The epithelial cells migrating from the explant or at the central portion of the epithelial sheeth, show original form even when they cultured in vitro, having densely distributed pigment-granules within them.
While, at the peripheral portion of the epithelial sheeth, the cell-form is rather irregular and the distribution of pigment granules is not so abundant, and a strong positive reaction to R.N.A. staining is recognized.
(5) Pigment-granule assumes a long bacilliform shape.
A certain regularity is recognized in the arrangement of the granules, which seems to indicate the drift of intracellular current.
(6) Silver impregnation technique by Masson and tyrosinase reaction were examined on the cultivated pigment epithelia of the retina. Each proved the existence of positive granules. It was confirmed that there is a certain rule as to where the pigment-granules are situated in the protoplasm.
(7) It may be given as a conclusion that pigment-granules are produced at the certain fixed region of the pigment-epithelium, through the medium of R.N.A. and move slowly onto their physiological seat drifted by intracellular current.
(8) Unlike other tissues, pigment-epithelia of the retina develop in a single larger even when cultured in roller tubes.
Chapter II
(1) Thyroid preperations and hormones such as Thyradin (below 0.5 mg/cc) and 1-Thyroxin (0.1 mg/cc), as well as testosterone (Enarmon 0.001--0.0001 mg/cc) and methyl-androstenediol (Megabion 0.1-0.01 mg/cc) among other sex hormones, remarkably accelerate the growth of the pigment-epithelia of the retina.
(2) Adreno-cortical hormones and preperations are highly suppressive for the epithelia to grow. Cited in the order of suppressiveness, they are : Hydro-cortisone, Cortisone, Interenin and DOCA.
(3) Pituitary hormones (ACTH, Prae-hormon and TSH) have no substantial influence on the growth of epithelia, nor have female hormones (Ova-hormon, Progenin)
(4) The results obtained from the planometric measurement of the growth, as mentioned above, are in conformity with the outcome of nucleic acid staining treatment.
(5) When thyroid hormones and methyl-androstenediol (Megabion) are supplied, the number of pigment-granules decreases. The pigment-granule assumes a subtle, long,

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