To pursue adrenal reserve in details, I administered adrenocorticotrophin (ACTH) -gel 40 I.U. once a day for 3 consecutive days in patients with various clinical conditions and compared the changes of 17-hydroxycorticosteroids (17-OHCS), 17-ketosteroids (17-KS) and 17-KS fractions of the studied patients with that of healthy subjects and patients with adrenal disorder. Microscale alumina column elution chromatography was used for the separation of urinary 17-KS, and Smith's modification of Reddy's procedure was employed for the estimation of urinary total 17-OHCS.
Following results were obtained
1) By the administrations of ACTH-Gel 40 I.U. for 3 consecutive days, the urinary excretion of 17-OHCS increased about 15-20 mg/day in healthy subjects, patients with Cushing's syndrome, hyperthyroidism, liver cirrhosis, and rheumatism, but did not in patients with Addison's disease and acromegaly with diabetes mellitus.
2) Though a little individual variations were observed, generally, in healthy subjects the urinary excretions of 17-OHCS were gradually increased, in patients with hyperthyroidism 3rd day's excretion were less than 2nd day's, in patients with secondary adrenocortical insufficiency and anorexia nervosa the increments of urinary 17-OHCS and 17-KS in 1st day were less (about 2 mg/day) but gradually increased in the 2nd and 3rd days, and in patients with hypothyroidism the 1st day's excretion was less than healthy subjects and much than secondary hypoadrenocorticism but the increments of urinary 17-OHCS in 2nd and 3rd days were less in 4 of 7 cases.
3) In Cushing's syndrome, urinary excretions of 17-OHCS increased but 17-KS did not by single administration of ACTH-Gel. However there were observed the increase of VI+ VII fraction (11-oxy-17-KS) and decrease of III fraction (dehydroisoandrosterone and its related compound). In a patient with adrenogenital syndrome due to bilateral hyperplasia, the administration of ACTH-Gel induced the increase of IV + V fractian (11-deoxy-17-KS) and decrease of VI + VII fraction.
4) The change of any fraction had not a correlation with that of urinary total 17-OHCS and 17-KS in patients with non-adrenal disorder.
5) There were no specific changes of 17-KS patterns by the consecutive administration of ACTH Gel in patients without adrenal disorder. From these results clinical significance of consecutive administrations of ACTH-Gel is evaluated and changes of steroids biosynthesis in adrenal cortex are discussed.

抄録全体を表示

In order to clarify the effect of estrogen on lipid metabolism, the levels of serum lipids and 24-hour urinary estrogen output were estimated in patients without evidence of liver and endocrine diseases in our clinic.
The following results were obtained :
1) There was inverse correlation between the urinary levels of estrogen and the serum concentrations of total cholesterol, esterified cholesterol, and the total cholesterol/phospholipid ratio.
2) In cases with high urinary levels of estrogen, the serum concentrations of non-esterified fatty acid and the serum lipoprotein index were low. But in cases with low urinary levels of estrogen, there was no consistent tendency in the serum concentrations of non-esterified fatty acid and the serum lipoprotein index.
3) Urinary levels of estrogen were not related to the serum concentrations of total lipid, free cholesterol, neutral fat, phospholipid, total fatty acid and the endogenous clearing activity.

抄録全体を表示

Using a stereotaxic apparatus, electrode was implanted into the hypothalamus of the dogs before experiments and the influence of the electrical stimulation on various areas of hypothalamus on the content of PBI¹³¹ in thyroid venous blood was studied. The dogs received intramuscular injection of about 100-500 microcuries of I¹³¹ 5 or 6 days before experiments. Thyroid venous blood was obtained by inserting the polyethylene catheter into the thyroid vein.
When the anterior hypothalamus and the median eminence was stimulated, definite increase of PBI¹³¹ was observed, while in hypophysectomized dogs, the stimulation of these areas did not promote the thyroid hormone secretion.
This would indicate that the increase of thyroid hormone secretion by the stimulation of the anterior hypothalamic area and median eminence is due to the increased secretion of thyrotropin from the pituitary gland.

抄録全体を表示

The important role of the anterior and posterior pituitary glands in the carbohydrate metabolism has been the leading subject in the study of diabetes mellitus. The detail elucidation of the mechanism of its hormonal influences has been much discussed with respect to component individual pituitary hormone. The author has tried to clarify the situation by using Warburg's in vitro technique. The experiment was carried out in three series, i.e., 1) direct experiment in which anterior and posterior pituitary hormones were added to the soaking medium of isolated tissue slices (diaphragm and liver) of Wistar strain rats ; 2) in vitro experiment with tissue slices of hypophysectomized rats ; 3) following the same procedures with tissue slices of rats pretreated with various anterior and posterior pituitary hormones.
Following items were studied as the indicator of carbohydrate metabolism of tissue slices in vitro.
a) Glycogen content of tissue slices prior to and after incubation.
b) Glucose utilization from the soaking medium.
For the pituitary hormones following preparations were used :
Adrenocorticotropic hormone (ACTH) : ACTH-SHIONOGI (Shionogi) or H.P. Acthar-gel (Armour), Growth hormone (GH) : GH-11, GH-12 (Shionogi laboratory) or Antuitrin-G (Parke Davis), Thyroid stimulating hormone (TSH) : Pretiron (Schering), Gonadotropic hormone (GTH) : Antex Leo or Physex Leo (Leo), Vasopressin : Vasopressin (Teikoku Hormone MFG.), Oxytocin : Atonin-O (Teikoku Hormone MFG.), Melanocyte stimulating hormone (MSH) MSH prepared by Dr. Kazuo Shizume.
The results of the experiments are summarized as follows :
A. Observations on hypophysectomized rats.
1) Hypophysectomized rats show hypoglycemia in fasting condition, their tissue glycogen content is decreased or apt to be decreased. Their diaphragmatic muscle shows increased ability in glucose utilization. Another characteristic is the loss of neo-glycogenetic capacity of their liver slices. With regard to insulin effect no specific enhancement was observed with tissue of hypophysectomized rats.
2) Pretreatment of hypophysectomized rats with ACTH or GH restores the above mentioned abnormalities to some extent. Particularly liver slices of hypophysectomized rats showed an enormous neo-glycogenetic restoration.
3) Injection of GH to hypophysectomized rats leads to fatal hypoglycemia. This apparent paradoxical effect of GH against ACTH was most noticeable.
B. Influence of ACTH.
1) Direct addition of ACTH to the soaking medium results in enhancement of glucose utilization of diaphragm and liver slices, as well as acceleration of neo-glycogenesis.
2) Injection of ACTH to the rats increases their liver glycogen content, and the diaphragm of thus treated rats shows increased ability for glucose utilization in vitro experiment.
3) In vitro pretreatment of liver slices with ACTH results in the marked enhancement of neo-glycogenesis of thus treated liver slices under the presence of insulin.
C. Influence of GH.
1) Injection of GH produces 3 different kinds of responses in blood glucose level as follows :
a. Hypoglycemia in hypophysectomized or adrenalectomized rats, b. Hyperglycemia in normal well fed rats or alloxan diabetic rats, c. Initial hyperglycemia followed by hypoglycemia in normal fasting rats.
Tissue glycogen content tends to increase after GH injection, particularly conspicuous in diaphragmatic muscle. Repeated injection of GH produce the decrease of glucose tolerance and insulin sensitivity, but are not themselves capable of producing experimental diabetes.
2) Tissue slices of rats pretreated in vivo with GH showed decreased glucose utilization, and this was most conspicuous in the diaphragm. Glycogen synthesis was not influenced significantly, but insulin effect in vitro was inhibited in both glucose utilization and glycogen synthesis.
3) Added GH to the soaking medium inhibited the glucose utilization of tissue slices,

抄録全体を表示

Using I¹³¹-TSH which was prepared by iodination, the relationship between TSH and thyroid gland, especially the mechanism of active and inactive TSH, the mode of action of Lugol's solution on Grave's disease and that of Mercazol (1-methyl-2-mercaptoimidazole) on thyroid, were investigated.
The results were as follows :
1) I¹³¹-TSH was made by the reaction between elemental iodine (I₂¹²⁷) and TSH (Pretiron), using radioiodine I¹³¹ as a tracer.
2) The saturatedly iodinated TSH was lost its biological activity with iodination, but many differently active TSH was possible to make by different grade of iodination.
3) TSH (Pretiron) 500 JS/18mg contained 5.15% of tyrosine, and 0.53% of tryptophan, while none of cysteine and iodine.
4) In TSH 1 JS, the amount of tyrosine was 1.83γ and TSH 1 JS was saturated by 2.5γ of iodine and then its activity was lost completely with iodination.
When tyrosine residue of TSH was iodinated, tyrosine residue was changed to DIT.
I₂ molecular weight/Tyrosine molecular weight =254.84/181.09=1.4/1
From this result it was ascertained that the experimental result was coincided with the theoretical value, that tyrosine residue only participated in the iodination of TSH and that absolutly necessary residue for the activity of TSH was tyrosine.
5) If the molecular weight of TSH was 10,000, 1 Mol of TSH would contain 2 or 3 tyrosine residue and this TSH would be saturated with 4 or 6 iodine.
6) In Graves disease which cause was seemed to be the hypersecretion of TSH from pituitary gland, it is presumed that the action of Lugol's solution is inactivation of TSH by the formation of iodinated TSH which was made in proportion to the elevated concentration of TSH.
7) The mechanism of action of Mercazol was mainly the inhibition of TSH iodination by the reduction of elemental iodine.

抄録全体を表示

Satisfactory results could be recognized by Estriol therapy in many patients suffering from climacteric disorders, premenstrual tension and dysmenorrhea.
The effectiveness was remarkable with a suitable increase in dosage according to the severity of the disease.
In climacteric disorders, 300γ dosis a day for seven days orally, in premenstrual tension and dysmenorrhea, 450γ dosis a day for seven days should be taken for effective treatment.
On application of this preparation, no noticeable side-effects could be recognized.

抄録全体を表示

Diabetes mellitus is a disease characterized by various metabolic disturbances primarily due to the relative or absolute deficiency of insulin in the body. In the present study, serum insulin activity was measured using rat diaphragm by Willebrands' method and was compared with various metabolic changes. Favorable response to the treatment of sulfonylureas was seen in patients showing extra-insulin secretion after the intravenous glucose loading. Anti-insulin factors were also investigated in severe diabetics and normal individuals and subclinical alloxan-diabetic and adrenalectomized rabbits treated with typhoid vaccine.
The results are summarized as follows :
(1) Contrary to the conclusion of Lawrence and his associates, low serum insulin activity was observed in about 60% of maturity-onset diabetics.
(2) Diabetics with infection or increased urinary excretion of ketone bodies showed generally diminished serum insulin activity.
(3) Close negative correlation was found between serum insulin activity and the 2nd hour level of blood sugar following glucose loading, although no significant correlation was found between serum insulin activity and the fasting blood sugar level or serum total cholesterol.
(4) Acetylating activity of p-aminobenzoic acid was decreased in patients with low serum insulin activity.
(5) Approximate linear relationship between regression coefficient following intravenous glucose loading and serum insulin activity was demonstrated in healthy subjects and in mild and moderate diabetics.
(6) Oral antidiabetics such as sulfohylureas and mesoxalate were not effective in diabetics with low serum insulin activity, but biguanides were effective in most diabetics with low serum insulin activity as well as those with high serum insulin activity.
(7) Secondary failure of sulfonylurea treatment developed more rapidly and more frequently in diabetics with low extra-insulin secretion.
(8) Adrenal glands seemed to have relation with anti-insulin factor in the sera of untreated severe diabetics and rabbits treated with typhoid vaccine.

抄録全体を表示

The effect on neurosecretion in accordance with the following various stimulation was studied in male albino rats using modified Halmi's aldehyde-fuchsin stain method.
A. 5 minutes exposure in water (summer and winter)
B. Coldness (-5°C) exposure after procedure A.
C. Local stimulation in skin :
1) TEN-KYU stimulation (mox-burn) in a part of tail-radix-skin (10 times for 8 minutes)
2) TEN-KYU stimulation in back-skin (10 times in every 6 part of back-skin for 25 minutes) D. 20 times SENKO stimulation (Buddhism flame) in a part of tail-radix-skin for 5 minutes. E. Darkness and Lamp stimulation (700 Lux) after 3 days darkness.
Results
1) 5 minutes water exposure in summer : The granules in neurosecretory center were remarkably decreased after 15 or 30 minutes and increased after 3 hours. Neurohypophyseal granules were decreased after 15 and 30 minutes.
2) Cold (-5°C) exposure in summer after 5 minutes exposure in water : After 15 or 30 minutes, the remarkable increasing of the granules in neurosecretory center was found. But after 30 minutes or 1 hour, the granules in infundibulum and neurohypophysis were much found.
3) In winter, no decreasing granule in neurohypophysis was found after 5 minutes-water-exposure. The other hand, in the secretory center, the granules on the axons were greater than the normal.
4) 1 hour after 10 times mox-burn in the tail-radix-skin, the granules in secretory center were decreased and the neurohypophyseal granules were slightly increased. But in back-skin mox-burn stimulation, the granules of the secretory center were remarkably increased and the neurohypophyseal granules were not affected after 1 hour. In accordance with SENKO flame stimulation, the granules in secretory center were remarkably decreased but the neurohypophyseal granules were not affected after 1 hour.
5) Group in constant darkness : The granule in secretory center was increased after 3 days, and it was decreased in 5 or 10 days after. And then it was also increased after 20 days, but the granule in neurohypophysis and infundibulum was decreased after 3 or 5 days and then it was recovered to the control group's after 30 days.
6) Constant 700 Lux light stimulation : Granule in nucl. paraventricularis increased after 2 or 3 hours and then remarkably decreased after 6 to 24 hours. But after 1 day, it began to recover gradually to normal value toward 2 days and it was increased over normal again on 3 to 5 days after stimulation. The granule in cytoplasm and along beaded fiber of nucl. supraopticus was decreased in 3, 4 and 5 days after. The neurohypophyseal granule was slightly increased in 1 or 2 hours later and then only slight change was found in its granule.

抄録全体を表示