Folia Endocrinologica Japonica
Online ISSN : 2186-506X
Print ISSN : 0029-0661
ISSN-L : 0029-0661
Volume 44, Issue 9
Displaying 1-10 of 10 articles from this issue
  • Minoru IRIE
    1968 Volume 44 Issue 9 Pages 977-986,961
    Published: December 20, 1968
    Released on J-STAGE: September 24, 2012
    JOURNAL FREE ACCESS
    Serial levels of Human Growth Hormone (HGH), glucose, and FFA were determined in various states of human subjects.
    I. HGH secretion in normal subjects:
    (1) After overnight fast and at bed rest during daytime, 9 subjects showed no significant change of HGH levels. In 8 hospital workers, with daily activity and meals, the elevation of HGH levels was observed 4 hours after breakfast. The HGH values at this time were widely distributed, but wider distribution was noted in younger (13-14) age group than other (over 15 and adults) group. This difference was more marked in males than females. (2) at night time, all 10 test subjects showed the elevation of HGH levels with the onset of sleep. HGH secretion appeared to be suppressed by the paradoxical sleep which was defined by brain wave. (3) In 5 subjects, blood was drawn at 40 minutes interval during 3 days fasting. Fluctuations and bursts of HGH levels were observed in all cases, and appeared to correlate with those of FFA.
    II. Influence to the HGH secretion of experimental modifications of metabolic states in normal subjects
    (1) In 28 subjects, insulin administration (0.1u./kg) caused marked increase of HGH levels. (2) Following 100 g glucose load in 21 subjects, HGH levels showed the secondary rise at 4 hours. (3) 25g of glucose infused intravenously for 20 minutes caused marked secondary rise, but the same amount of glucose infused for 3 minutes caused only slight rise. The results suggest that the changing of blood glucose level per se may not directly be correlated with the level of HGH. (4) L-arginine administration (20g) caused marked elevation of HGH levels in 5 cases. (5) Ingestion of 70g cheese in 6 subjects caused rise of HGH between 150 and 240 minutes. (6) Ingestion of 50g butter in 6 subjects caused no change of HGH levels. (7) For the purpose of decreasing FFA levels, intravenous administration of nicotinic acid (100 mg×2) was performed in 17 subjects. There was a temporary decrease of FFA, followed by a marked secondary rise. HGH levels showed marked increase in all subjects. Changing the manner of administration (100 mg×5) caused no essential difference on the rise of HGH levels. In 7 cases, with the combination of nicotinic acid and heparin injection, which inhibited the fall of FFA levels, the rise of HGH was clearly suppressed. The secondary rise of FFA was less than the cases of nicotinic acid injection alone. (8) Oral administration of 3.3 g of acetylsalicylic acid in 6 subjects also caused the rise of HGH levels. (9) Administration of heparin could not suppress the HGH rise caused by insulin or arginine administration. These results suggest that the decrease of FFA level is one of the stimulus for the secretion of HGH.
    III. Clinical investigations :
    (1) Patients with hypopituitarism caused no change of HGH levels following insulin (18 cases), arginine (6 cases), and nicotinic acid (6 cases) administrations. The marked decrease of the secondary rise of FFA following nicotinic acid or arginine administration in these patients was observed. These results suggest that the secreted HGH participate in inducing the secondary rise of FFA in these conditions. (2) Among 14 diabetic patients who had glucose infusion for 3 minutes, 9 patients showed marked rise of HGH levels. 4 out of 5 borderline cases showed marked rise. (3) In 6 obese patients, nicotinic acid administration caused no increase of HGH levels. The continuation of the secondary rise of FFA in these patients was less than the control normal subjects. These results of diabetes and obesity suggest some implication of the abnormality of HGH secretion in these states.
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  • Haruo IWATSUBO, Kiyoshi MIYAI, Yoshiaki OKADA
    1968 Volume 44 Issue 9 Pages 987-992,963
    Published: December 20, 1968
    Released on J-STAGE: September 24, 2012
    JOURNAL FREE ACCESS
    The effects of stress, exercise and other factors on human growth hormone (HGH) secretion were investigated in normal subjects and various disorders. Plasma HGH was measured by chromatoelectrophoretic radioimmunoassay.
    1) Exercise : Exercise by double two step test of Master was associated with a slight increase of HGH secretion only in female, but successively 6 times of the test with a remarkable increase both in female and in male. This rise of plasma HGH level was accelerated by arginine infusion or beef ingestion.
    2) Operation : Major abdominal surgery under general anaesthesia with Fluothane and nitrous oxide was followed by a remarkable elevation of plasma HGH with a peak at 60-90 minutes after the operation started. On the other hand, brain operation under the same anaesthesia but with hypothermia did not lead to significant changes or rather led to decrease in plasma HGH while cooling, but to a remarkable increase as rewarming commenced.
    3) Cold Exposure : No increase in plasma HGH level was found during exposure of normal subjects to 4°C for 1-2 hours but a significant elevation of plasma HGH level was observed following recovery to room temperature (23°C).
    4) Drugs : Intravenous injection of 35 mg of histamine caused a moderate increase in plasma HGH. In 6 of 8 normal subjects, simultaneous injection of aminophylline enhanced the increased response of plasma HGH by insulin-induced hypoglycemia.
    5) HGH secretion in primary hypothyroidism : Plasma HGH response to hypoglycemia and exercise (two step test) was significantly lower in patients with untreated primary hypothyroidism than in normal subjects.
    6) HGH secretion in hypopituitarism : Studies on secretion of trophic hormones in hypopituitarism showed that, of 12 patients, panhypopituitarism was found in 3 cases, partial deficiency in 8 and selective ACTH deficiency in 1. Of 9 subjects with pituitary dwarfism, panhypopituitarism was found in 1 case, partial deficiency in 5 and isolated GH deficiency in 3, of which two cases were siblings.
    Some cases, of which basal HGH secretion was detectable at overnight fast and suppressed by glucose administration, showed a dissociative response to various stimuli : a significant elevation of HGH level by arginine infusion despite no responses to insulin or pyrogen injection. Others showed parallel responses to such various stimuli as insulin induced hypoglycemia, arginine infusion and or exercise.
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  • Akira MATSUOKA, Yoshiaki FUJISAWA
    1968 Volume 44 Issue 9 Pages 993-1000,964
    Published: December 20, 1968
    Released on J-STAGE: September 24, 2012
    JOURNAL FREE ACCESS
    We measured the plasma human growth hormone (HGH) levels by the radioimmunoassay using a double antibody method described by Schalch & Parker. We evaluated HGH secretion from pituitary mainly by plasma HGH response to insulin induced hypoglycemia. As the criteria of fall of blood sugar and rise of plasma HGH levels the following indices were used. The index of fall of blood sugar
    = The maximal blood sugar decrements / The time needed for reaching the minimal blood sugar value
    (The mean normal range of 12 control subjects was 1.98±0.86) The index of rise of plasma HGH
    The maximal plasma HGH increments / The time needed for reaching the maximal plasma HGH level
    (The mean normal range of 12 control subjects was 0.63±0.36)
    a. The effects of metabolic changes in diabetes mellitus. We investigated the HGH response to insulin in diabetes. The results were as follows :
    (1) We observed high fasting blood sugar in diabetes and the lower than normal HGH response to insulin.
    (2) There was correlation between decrements of blood sugar and HGH response to insulin although the variations of HGH responses were markedly greater.
    (3) We couldn't recognize a correlation between the increments of HGH and hypoglycemic symptoms by insulin.
    (4) In severe class of diabetes classified from glucose tolerance curve, the HGH response to insulin was decreased.
    (5) In diabetes with nephropathy and/or retinopathy the HGH response to insulin was shown to be lower than in non-complicated diabetes.
    (6) The highly obese patients with and without diabetes demonstrated a smaller HGH response to insulin as compared with the non-obese patients. The lean patients also showed a smaller HGH response to insulin.
    During above investigations we encountered often presence of insulin antibody and impaired fall of blood sugar by insulin in diabetics, so there have been left certain unsolved problems about methodological viewpoint to evaluate HGH secretion from pituitary in diabetes from these investigations.
    b. Clinical studies of plasma HGH in patients with hypothalamopituitary disease
    Patients with acromegaly showed elevated fasting HGH levels and especially three cases with diabetes showed significantly elevated values such as 480,470 and 182 mug/ml respectively. In almost all of patients with hypopituitarism, chromophobe adenoma, craniopharyngioma and diabetes insipidus, normal fasting HGH levels were observed. In all cases of six patients with chromophobe adenoma, an impaired or absent HGH response to insulin was observed. In five insulin test examined on four patients with craniopharyngioma, three tests showed good HGH response and two tests no response to insulin. In six insulin tests examined in three patients with diabetes insipidus, the results were variable. We have made a long term follow up study of plasma HGH level in a male acromegalic, 34 years old, who was treated with repeated CO60 irradiation. HGH level showed corresponding fall after irradiation.
    c. The effects of endocrine changes following administration of corticosteroid and ACTH
    In five non-endocrine patients receiving corticosteroid therapy, plasma HGH response to insulin were examined. Four patients showed an impaired or failing plasma HGH response to insulin. Following Friedman's report (Lacet II : 568, 1966), we investigated plasma HGH levels after administration of ACTH. 0.125 or 0.250 mg of β1-24 ACTH was injected intramuscularly to six subjects. A consistent secretary pattern of HGH from pituitary was not shown for three hours, but a tendency to elevate plasma HGH was shown in four cases. We also administered 1 mg of β1-24 ACTH-Z. Six of ten cases tested, showed a tendency of elevation of HGH levels from two to six hours after the injection. Two under six subjects administered with commercial ACTH showed also similar pattern.
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  • Kazuo SHIZUME
    1968 Volume 44 Issue 9 Pages 1001-1006,966
    Published: December 20, 1968
    Released on J-STAGE: September 24, 2012
    JOURNAL FREE ACCESS
    The development of radioimmunoassay for growth hormone made the diagnosis of acromegaly easier and more accurate. Serum growth hormone (GH) concentrations in 31 fasting patients with active acromegaly were all above 15 mμg/ml, while in most cases of normal subjects they were below 5 mμg/ml. Besides cases of acromegaly, abnormally high values were observed in 3 cases of insuloma and in 3 cases of anorexia nervosa. Occasionally, fasting serum GH concentration is high due to the influence of psychological stress or physical exercise. However, in normal subjects, even if such influences cause one specimen to be high, repeated specimens on different days show normal values. On the contrary, cases of acromegaly show high values on all specimens. In addition, high values of fasting serum GH concentration in normal subjects decreased to normal values following administration of glucose, but they remained high in acromegaly.
    In 3 patients with acromegaly, serum GH level was followed before and after treatment by 60Co irradiation or by surgery. It was observed that GH level decreased with clinical improvement and increased again with relapse.
    GH level was also measured in acromegalic patients who had received treatment in the past. Most of the patients who had received radiation therapy showed high values, thus indicating that conventional radiation therapy is incomplete in most cases. In patients who had received surgical treatment, relatively low values were observed; however, only one-third of them showed values below 5 mμg/ml. Among these patients, those whose values were below 10 mμg/ml, showed no clinical symptoms of acromegalic activity, and in most cases no increase of GH level was observed in response to insulin hypoglycemia. In these cases, the total daily GH secretion may be within normal range and they may need no further treatment. This should be studied in the future.
    It has been reported that estrogen is beneficial in the treatment of acromegaly. The effect of estrogen on serum GH level was studied in 3 patients with acromegaly and no change of GH level was observed. Therefore, it was concluded that estrogen is effective by suppressing the action of growth hormone in peripheral tissue.
    Diagnosis of conventional pituitary dwarfism can be made accurately by measuring the serum GH level by radioimmunoassary, and it is now possible to diagnose even pituitary dwarfism due to selective growth hormone deficiency. Fasting serum GH concentration was measured in variety of cases of dwarfism. Among 14 cases of pituitary dwarfism, GH was not detectable in 10 cases, and in the other 4 cases it was below 1.5 mμg/ml. Although in most of cases non-pituitary dwarfism, GH was detectable, in some cases it was undetectable. In the latter cases, examination of growth hormone response to insulin hypoglycemia is very effective in differentiating pituitary dwarfism from other kinds of dwarfism. In all normal subjects and cases of non-pituitary dwarfism, significant increase of serum GH level was observed. No increase was observed in 18 cases of pituitary dwarfism. Although a definite response was observed in 4 cases of thyroid dwarfism and in 6 cases of Turner's syndrome, it was a relatively weak response compared with that of normal subjects. Growth hormone response to arginine injection is also useful in differentiating pituitary dwarfism from non-pituitary dwarfism. Definite and significant increases of serum GH concentrations were observed in 5 normal subjects, while no increase was observed in 4 cases of pituitary dwarfism.
    Parker et al. have reported serum GH increases in some cases of pituitary dwarfism in response to either insulin hypoglycemia or arginine infusion. A 20-year-old boy clinically suggesting pituitary dwarfism was observed. Although this patient showed a moderate serum GH increase in response to insulin hypoglycemia,
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  • I. Studies on the adrenocortical stimulating effects of synthetic β1-24ACTH preparations
    Yoshiyasu SAKO
    1968 Volume 44 Issue 9 Pages 1007-1015,968
    Published: December 20, 1968
    Released on J-STAGE: September 24, 2012
    JOURNAL FREE ACCESS
    In order to evaluate the clinical usefulness of synthetic β1-24 ACTH preparations (Ciba 30'920-Ba and Ciba 36'716-Ba), their adrenocortical stimulating effects were compared with those of natural ACTH preparations by measuring daily urinary 17-OHCS excretion. Urinary 17-OHCS excretion was measured by means of a modification of the method of Reddy, Jenkins and Thorn.
    1) The 8-hour intravenous infusions of 25 I.U. of NH-ACTH (Organon) and 0.25 mg. of Ciba 30'920-Ba were performed at intervals of 4 days in 7 patients with various diseases and 2 normal subjects. These two ACTH preparations showed almost the same adrenocortical stimulating effects on the same subjects. Mean daily urinary 17-0HCS excretions in 9 subjects were 4.21 mg./day on the 2 days before, 13.7 mg. on the day of and 4.08 mg. on the day after the administration of 25 I.U. of NH-ACTH. With the administration of 0.25 mg. of Ciba 30'920-Ba, they were 4.13 mg./day, 13.7 mg. and 4.55 mg., respectively.
    2) Five patients who had shown local and/or general allergic reactions to the intramuscular injection of ACTH-Z (Organon) gave positive skin reaction to NH-ACTH, and 4 of these patients gave positive skin reaction to highly purified ACTH (HP-ACTH, Organon), too. However, none of them gave positive skin reaction to Ciba 30'920-Ba. Three patients who were hypersensitive to NH-ACTH received 0.25 mg. of Ciba 30'920- Ba without showing any side effect and their urinary 17-OHCS increased significantly.
    3) Intramuscular injections of 25 I.U. of Ciba 36'716-Ba for 3 successive days caused only a slight increase in urinary 17-OHCS in 8 normal subjects, but 50 I.U. of this preparation administered in the same way brought about a significant increase in 8 normal subjects. This increase corresponds in amount to that caused in 10 normal subjects by 20 I.U. of ACTH-Z administered in the same way.
    4) A single intramuscular injection of 100 I.U. of Ciba 36'716-Ba caused an increase in urinary 17-OHCS which lasted for 3 days. These results seem to support the therapeutic usefulness of this preparation.
    It is concluded that the synthetic ACTH preparations have an advantage over the natural ACTH in clinical use.
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  • II. Studies on the suppression test of the pituitary-adrenocortical system
    Yoshiyasu SAKO
    1968 Volume 44 Issue 9 Pages 1016-1024,969
    Published: December 20, 1968
    Released on J-STAGE: September 24, 2012
    JOURNAL FREE ACCESS
    In order to evaluate the usefulness of dexamethasone suppression test for the diagnosis of certain clinical disorders which show elevated urinary 17-OHCS excretion, the effects of small and large doses of dexamethasone on urinary 17-OHCS excretion were studied in normal subjects, patients with simple obesity, Cushing's syndrome and hyperthyroidism. Urinary 17-OHCS excretion was measured by means of a modification of the method of Reddy, Jenkins and Thorn. Dexamethasone was administered for 9 days in the following way : 1.0 mg. daily for 3 days, 2.0 mg. daily for 3 days and 8.0 mg. daily for 3 days, in 4 divided doses.
    1) Urinary 17-OHCS excretion in 5 normal subjects and 7 patients with simple obesity was suppressed by a daily administration of 1.0 mg. of dexamethasone for 3 days. Urinary 17-OHCS was rather more markedly suppressed in patients with simple obesity than in normal subjects.
    2) Urinary 17-OHCS excretion in 2 patients with Cushing's syndrome due to bilateral adrenocortical hyperplasia was not suppressed by the daily administration of 1.0 mg. of dexamethasone for 3 days. Therefore, Cushing's syndrome in patients can be clearly differentiated from normal subjects or patients with simple obesity by this test. Urinary 17-OHCS excretion was occasionally suppressed in patients with Cushing's syndrome by the daily administration of 2.0 mg. of dexamethasone for 3 days. It seems to be pertinent, therefore, to administer 1.0 mg. of dexamethasone daily for the purpose of differentiating Cushing's syndrome from simple obesity.
    3) Daily administration of 8.0 mg. of dexamethasone for 3 days did not suppress urinary 17-OHCS excretion in 3 patients with Cushing's syndrome due to adrenocortical adenoma, but suppressed it to the level lower than 5.0 mg. /day in 2 patients with bilateral adrenocortical hyperplasia. Therefore, adrenocortical adenoma can be differentiated from bilateral adrenocortical hyperplasia in Cushing's syndrome by giving 8.0 mg. of dexamethasone for 3 days.
    4) Suppressibility of the daily urinary 17-OHCS in 6 patients with hyperthyroidism was almost equal to that in normal subjects by the daily administration of 1.0 mg. of dexamethasone for 3 days, although the actual values of the daily urinary 17-OHCS were higher than those of normal subjects.
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  • III. Studies on the suppression of the pituitary adrenocortical function after long-term glucocorticoid treatment
    Yoshiyasu SAKO
    1968 Volume 44 Issue 9 Pages 1025-1036,970
    Published: December 20, 1968
    Released on J-STAGE: September 24, 2012
    JOURNAL FREE ACCESS
    The purpose of the present study is to clarify the patho-physiology of the pituitary-adrenocortical insufficiency induced by glucocorticoid treatment, and to find out preventive means against this pituitary-adrenocortical insufficiency. Pituitary adrenocortical function in patients with various non-endocrine disorders who had been treated with glucocorticoid for long terms, was studied by measuring daily urinary 17-OHCS excretion. Urine samples were collected daily for a period of 12 days beginning from the 1st day after glucocorticoid treatment was stopped. Oral SU-4885 test (3.0 gm./day in 6 divided doses) and intramuscular ACTH stimulation test (20 I.U. of ACTH-Z for 3 successive days) were performed on the 3rd test day and 9-11th test days, respectively. Urinary 17-0HCS excretion was measured by means of a modification of the method of Reddy, Jenkins and Thorn.
    1) Eighteen subjects after long-term glucocorticoid treatment were studied.
    a) Seven patients treated with less than 2000 mg. (prednisolone equivalent) of glucocorticoid in a total dose and for less than 12 months, gave variable results, but many of them showed reduced response to SU-4885 and delayed response to ACTH. These results suggest that glucocorticoid treatment brings about secondary adrenocortical insufficiency by its suppressing effect on pituitary ACTH secretion.
    b) Eight out of 11 patients treated with more than 3000 mg. of glucocorticoid in a total dose and for more than 12 months, showed reduced response to SU-4885 and delayed or reduced response to ACTH. Four of these 8 patients treated with glucocorticoid for more than 20 months, showed reduced responses to SU-4885 and to ACTH.
    c) The remaining 3 patients who were maintained with a daily dose of less than 5 mg. of prednisolone for more than one year before the cessation of the treatment showed normal response to SU-4885. There seemed to be a reverse relationship between final daily dose of glucocorticoid and response to SU-4885.
    d) A patient treated with glucocorticoid for 3 years showed reduced pituitary adrenocortical function even on the 53rd day after the cessation of the treatment. It seems to take a long time to recover from the pituitary-adrenocortical insufficiency after longterm glucocorticoid treatment.
    2) In comparison with the administration of glucocorticoid alone, a combined administration of 20 mg. of H.M.D. daily with glucocorticoid in 4 patients caused no significant change in response to SU-4885 but gave a better response to ACTH after the cessation of the treatment. Daily urinary excretion of 17-OHCS was measured in subjects treated with gradually reducing doses of betamethasone alone or in combination with 20 mg. of H.M.D. daily for 4 weeks. Although the decrease of urinary 17-OHCS during the treatment seemed to be more marked in the betamethasone-H.M.D. group than in the betamethasone group, the increase of urinary 17-OHCS after the cessation of the treatment appeared sooner in the betamethasone-H.M.D. group. These results lead to a conclusion that the combined administration of anabolic steroids with glucocorticoid may partially improve the pituitary adrenocortical hypofunction after glucocorticoid treatment.
    3) Treatment with a daily dose of 20 I.U. of ACTH-Z for 5 successive days immediately before the cessation of glucocorticoid treatment in 4 patients improved the response to ACTH-Z, especially to the first dose of ACTH-Z, but showed the reduced response to SU-4885. This may be due to the fact that ACTH administration suppresses pituitary ACTH secretion in spite of the improvement of adrenocortical reserve.
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  • Atsushi ABE
    1968 Volume 44 Issue 9 Pages 1037-1055,972
    Published: December 20, 1968
    Released on J-STAGE: September 24, 2012
    JOURNAL FREE ACCESS
    It has been suggested that there is close relationship between obese subjects and maturity onset diabetes from William's and Ogilvie's reports.
    In the present study, this relationship between obesity and diabetes mellitus examined by determining the plasma insulin responsiveness of normal weight and obese, nondiabetic and diabetic subject to oral glucose loading. These plasma insulin were measured by three methods : the value of the rat diaphragm assay = DILA, the value of the rat epididymal fat pad assay = FILA, and the value of the radio-immunoassay = IRI.
    By comparison among these three assayed values, the investigation was undertaken to study about the effect of obesity on insulin activity.
    In comparison with normal subjects, non-obese diabetics in fasting and after oral glucose loading, exhibited the low DILA, elevated FILA, slightly elevated IRI with delayed peak. It was considered that this pattern of assayed values by three methods resulted from diabetes mellitus and represented a diabetic changes. Obese diabetic subjects more definitely manifested these diabetic changes on the insulin responsiveness to glucose loading by three methods.
    Despite the normal glucose tolerance, obese subjects had also diabetic changes on the insulin responsiveness by three methods.
    This investigation had shown that the decrease in plasma NEFA following glucose administration was slower and smaller in obese and obese diabetic subjects than in normal subjects.
    From these findings, it supposed that the high plasma NEFA levels following glucose loading gave the diabetic pattern on the insulin responsiveness by three methods.
    Then for the purpose of observing what effects were made by the high plasma NEFA on the insulin activity by three methods, the rabbits fed high fat diet for fifty to seventy days. It noted that the high fat diet fed rabbit became obesity and had fasting high plasma NEFA concentration and disturbing the decrease of plasma NEFA following glucose loading.
    The plasma of rabbit which had high NEFA concentration showed the same diabetic pattern of insulin activity by three assay methods as that of the obese human subjects.
    To study the effect of NEFA on the biological insulin activity to muscle and adipose tissue in vitro, the elevated plasma NEFA were obtained from the obese rabbits following intravenous heparin injection after seventy days fed high fat diet. This elevated plasma NEFA exhibited the pattern of insulin activity that DILA was low, FILA was elevated and IRI was unchangeable.
    From these findings, it became evident that the high NEFA concentration produced the diabetic insulin responsiveness (i.e. low DILA, elevated FILA and IRI) on plasma of the obese subjects.
    Generally speaking, obesity had a normal glucose tolerance, however
    1) obesity showed diabetic changes on the insulin responsiveness by three insulin assay methods,
    2) obesity exhibited abnormal fat metabolism with fasting high NEFA levels and disturbing of decrease in plasma NEFA following glucose administration.
    3) obesity had a insulin resistance to muscle glucose metabolism (DILA↓) 4) obesity demanded the increased insulin secretion from pancreatic β-cells (IRI↑).
    From these points obesity might become the diabetic stress and might caused one who had a family history of diabetes mellitus and fragile pancreatic β-cell, diabetes mellitus.
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  • Munetada OIMOMI
    1968 Volume 44 Issue 9 Pages 1056-1075,974
    Published: December 20, 1968
    Released on J-STAGE: September 24, 2012
    JOURNAL FREE ACCESS
    Increasing evidences are showing the importance of the hypothalamus for the regulation of ACTH secretion from the pituitary. In this report the author has tried to investigate the functional pattern of the Hypothalamo-Pituitary-Adrenal system of the rat, which is expected to operate under various noxious conditions, adrenalectomy with and without prednisolone treatment, furthermore ACTH administration. For the follow up study of the Hypothalamo-Pituitary-Adrenal system special attention was paid for the analytical study of the individual organ in the system.
    For this purpose direct assay of Corticotrophin Releasing Activity (CRA) in the Median Eminence (M.E.) and also direct assay of the plasma and pituitary ACTH-like activity and simultaneous determination of plasma and adrenal corticosterone level were carried out. CRA of the crude M.E. extract (M.E.E.) prepared with cold glacial acetic acid following the description of Vernikos-Danellis was determined by the in vitro assay technique, which was described by Tsuji-Nakai (Folia Endocrinologica Japonica 43 : 957, 1968)
    This method is based on the ACTH assay technique after Tsuji-Yasui, of which, specificity, high sensitivity and reproduce-ability experienced carefully checking.
    Three halves of rat pituitary were placed in one flask and incubated for 60 minutes at first (pre-incubation) and then M.E.E. described above was added to the incubation medium.
    After final incubation for 60 minutes ACTH secreted in the medium was determined after Tsuji-Yasui's bioassay method of ACTH.
    As control experiment it was checked, if the crude M.E.E. used in this experiment has any ACTH-like activity from the view point of corticoidogenic action (Folia Endocrinologica Japonica, 41 : 643, 1965).
    It was observed, that extra large dosis of M.E.E., such as corresponding to 20 M.E.E. and also 150 mu lysine-8-vasopressin checked with in vitro assay exhibited ACTH-like activity, but small dosis of M.E.E. such as corresponding to 2M.E.E. as is usually used for the in vitro CRA assay system exhibited no ACTH-like activity in itself.
    Therefore the author has chosen the quantitative fluctuation of CRA in 2M.E.E. as for the parameter for the qualitative evaluation of CRA in given hypothalamus.
    The rat were exposured to various noxious stimuli, such as 1.) exposure to ether vapour for one minute, 2.) laparotomy, 3.) intermittent bell alarming for 3 min. duration, 4.) intravenous histamine, and 5.) subcutaneous epinephrine administration.
    The quantitative changes of CRA after these stimuli were followed up along with the simultaneous investigation of other parameters of Hypothalamo-Pituitary-Adrenal function.
    The results are summarized as follows :
    1) CRA showed elevated activity already 2.5 or 5 minutes after various kinds of stimuli. Other parameters of Pituitary-Adrenal function, particularly ACTH-like activity of pituitary and plasma, showed increased value following the primary elevation of CRA.
    The conclusion drawn was that, the hypothalamus is the final common pathway of various kinds of noxious stimuli and the very change of CRA in the median eminence of hypothalamus seems to regulate the Hypothalamo-Pituitary-Adrenal function.
    2) As far as this experiment is concerned lysine-8-vasopressin seems to act directly upon hypothalamus and to release CRF.
    But from the result of control experiment a partially direct effect upon pituitary as a sort of CRF for itself could not be excluded.
    3) Comparing studies of the ACTH secretion during 2.5 min., 7 min., and 15 min., following various kinds of stimuli disclosed the presence of different pattern of ACTH se-creation following different kinds of stimuli.
    These results strongly point out the importance of direct investigation of ACTH-like activity of plasma, not of the indirect follow up of pituitary function through plasma steroid level.
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  • 1968 Volume 44 Issue 9 Pages 1076-1086
    Published: December 20, 1968
    Released on J-STAGE: September 24, 2012
    JOURNAL FREE ACCESS
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