Circulating carcinoembryonic antigen (CEA), calcitonin (CT) and adrenocorticotropic hormone (ACTH) and levels in tissue extracts of a patients with Sipple's syndrome were measured simultaneously. Biofocal medullary carcinoma of the thyroid gland (MCT), left adrenal phaeochromocytoma and ectopic paraaortal phaeochromocytoma had been removed in the first operation. Total thyroidectomy was performed thereafter. Evidence has been presented showing that (1) the first operation lowered the elevated serm levels of CEA and CT, and levels of CEA and CT in tissue extracts of MCT were considerably higher than those of tumor-uninvolved thyroid tissue and phaeochromocytomas (2) markedly elevated levels of plasma ACTH were normalized by the first surgery and, in addition, immunoreactive ACTH and beta-melanocyte stimulating hormone (β-MSH) were detected in the phaeochromocytomas removed.
This is a documented case of the simultaneous production of CT and CEA by MCT associated with ectopic secretion of ACTH and β-MSH from the phaeochromocytomas without manifesting clinical features of Cushing's syndrome and is based on the findings referred to above.

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The isolation of pancreatic islets from collagenase-digested Wistar rat pancreas was shown by the sedimentation method at a unit gravity using Percoll solution with a density of 1.041g/ml. The density of digested exocrine tissues was in the range of 1.013-1.041g/ml, while that of purely isolated islets was in the narrow range of 1.066-1.075g/ml. More than a hundred islets were obtained freely from each rat pancreas without any gross contamination of digested exocrine tissues. A significant increase was observed in glucose-stimulated insulin release from islets isolated with Percoll in the same pattern as that without Percoll.
In addition to the well preserved morphology and function of pancreatic islets isolated by Percoll, the simplicity of the technique strongly commends the usefullness of this method.

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Wistar Female rats bearing DMBA induced mammary tumours were subjected to whole body hyperthermia 42°C dry heat exposure for 15 minutes daily for 6 weeks. The control group was maintained at a room temparature of 25°C. Hyperthermia induced significant growth stimulation of breast tumour compared to the controls. Plasma estradiol was slightly decreased while total T₄ and TSH values remained unchangedin heat stressed rats. Plasma prolactin was significantly increased together with enhanced synthetic activity of pituitary prolactin cells. It is concluded that heat acting as stressor accelerates breast tumor growth, probably by influencing synthesis of prolactin. Therefore the hormone dependancy of tumours should be considered before hyperthermia is used as an anticancer modality.

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The heterogeneity of glucagon and insulin in plasma and tissue extracts from a 57-year-old female with glucagonoma syndrome with surgically and autopsy verified islet-cell tumors was studied by Bio-Gel P-10 filtration. The preoperative plasma immunoreactive glucagon (IRG) level was 20.2ng/ml, and plasma glucagon-like immunoreactivity (GLI) 25.8ng/ml. The column chromatography of the preoperative plasma revealed three or four IRG components and four GLI components. Among these, peak II, the large glucagon immunoreactivity (LGI) peak, considered a candidate for proglucagon, was prominent, along with peak III.
The resected metastastatic liver tumor contained an enormous amount of IRG and an appreciable amount of immunoreactive insulin (IRI), indicating that the elevated plasma IRG was mainly of tumor origin.
The IRG pattern of the tumor tissue extract revealed a small quantity of IRG in peaks I and II, and a large amount in peak III; control pancreatic tissue extract manifested a similar elution pattern. The IRI elution pattern of the tumor tissue extract revealed two major IRI peaks which migrated close to the elution volume of cytochrome C and insulin, respectively. This is a quite different pattern from the control pancreatic tissue extract in which the IRI peak was localized in the elution volume of the insulin.
We conclude that the present metastatic liver tumor produced not only enormous amounts of glucagon but heterogeneous peptides which contained immunological insulin determinants within thei.

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The immunological heterogeneity of calcitonin (CT) was examined in fractions separated by gel filtration (Bio Gel P-30) from plasma and urine samples of two patients with medullary carcinoma of the thyroid obtained after calcium infusion and after thyroidectomy. Five distinct forms of immunoreactive CT were observed bygel filtration of plasma before treatment; one was eluted with the monomer CT and the other four were of higher molecular weight. The concentrations of all fiveforms increased during calcium infusion (4mg/kg, 10min) and decreased after the infusion, accompanied by a rapid change in concentration of the monomer form. After thyroidectomy, the level of the monomer form decreased faster than the levels of other forms. The main form in the urine was eluted in the same portion as abigger form (IIIb) in the plasma, not with the monomer form, after throidectomy.One antiserum (antiserum I) gave a higher estimation for the IIIb form and the predominant form in the urine than another antiserum (antiserum II). These findings suggest the identity of these two forms. Blood CT in various forms, including the monomer, may be converted to form IIIb in the kidney and exreted in that form.

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A 24-yr-old male patient had suffered from chronic tetany since school age. At the age of 20 tetanic convulsions occurred due to hypocalcemia. His mother also had chronic tetany due to pseudohypoparathyroidism. At the age of 24, hypocalcemia caused by pseudohypoparathyroidism was noted. Hypopotassemia persisted even when the hypocalcemia improved with the administration of 1α-hydroxycholecalciferol and calcium lactate. Other findings were normal blood pressure, high levels of plasma renin activity and serum aldosterone, a fall in blood pressure after angiotensin II antagonist infusion, blunted pressor response to angiotensin II infusion and hyperplasia of the juxtaglomerular cells. These results were compatible with Bartter's syndrome. Plasma prostaglandins E₂ and F_2α in standing position were suppressed after indomethacin administration.
To our knowledge this is thought to be the first report of a case of pseudohypoparathyroidism associated with probable Bartter's syndrome.

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Plasma luteinizing hormone (LH), progesterone, testosterone and estradiol concentrations were measured from the same 10 male and 10 female chickens at various ages of 28 to 1141 days. They were kept on a photoperiod of 14L: 10D (lights on 0500-1900h) and bled at 1400h.
In the female, plasma levels of LH and estradiol rose from 4 weeks of age to sexual maturity, and both reached peaks shortly before the onset of egg production, and dropped radidly thereafter. Either plasma progesterone or testosterone showed a similar change to that of LH or estradiol, except that the two hormones reached their peaks shortly after the onset of egg producttion. The plasma LH level dropped a little but was maintained at a fairy high level after one year of age, whereas the progesterone level dropped and reached a trough at one year of age, and fluctuated thereafter. The plasma testosterone level was very low and showed a sudden fall at one year of age, and remained at a low level thereafter. The plasma estradiol level showed a rise after one year of age, and fluctuated thereafter. The egg production rate reached a peak a month after the onset of laying and decreased with the advance of age. Positive correlations were observed between the egg production rate and LH, progesterone and testosterone concentrations, and a negative one between the egg production rate and estradiol concentration. It is postulated that the decrease in the egg production rate due to age is caused by a decrease in ovarian function rather than decrease in pituitary gonadotropic function.
In the male, LH levels rose during the prepuberty stage, reached the first peak at 238 days of age, and fluctuated thereafter with 3-5 fold higher values than those in the female at corresponding ages. Plasma progesterone levels fluctuated and showed four peaks, the values being higher than those of the female. Plasma testosterone levels were 10-20 times as high as those in the female, being low before sexual maturity, and reaching the first peak 2-3 months after sexual maturity. Plasma estradiol in the male was not detectable throughout the entire experimental period.

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We studied the insulin binding of erythrocytes from 26 “wellcontrolled” (FBG<120mg/dl), and 28 “poorly-controlled” (FBG<120mg/dl) non-obese diabetic patients, and 51 age-matched normal subjects. The capacity of insulin receptors was significantly decreased in well controlled (33.7±2.2) and poorly controlled (32.4±2.3) groups compared with normal subjects (43.1±2.3sites/cell), while fasting insulin levels of diabetics were comparable to normal subjects but their insulin response to a glucose challenge was considerably decreased. However, the “empty sites” affinity (Ke) was significatnly increased in both the well controlled group (5.2±0.3) and the poorly controlled group (4.8±0.3) compared with normal subjects (4.0±0.2×10⁸M^-1). Thus, the capacity of insulin receptors to bind erythrycytes was decreased but binding affinity was increased in hypoinsulinemic diabetics. The amount of insulin bound in well-controlled diabetics was comparable to that in control subjects at physiological insulin concentrations.

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Insulin binding to erythrocytes from normal subjects over a wide range of ages (group I, cord blood group II, Age 6M to 6 yrs group III, 7 to 19 yrs group IV, 20 to 59 yrs, group V, over 60 yrs of age) was determined using modified Gambhir's method and the effect of age and sex on the binding was evaluated.
The highest insulin binding to cord blood erythrocytes was accounted for by the increased number of reticulocytes since there was a highly significant correlation between insulin binding and the reticulocyte count (r=0.928, p<0.001). Group IV showed significantly higher binding than younger age groups II and III. The mean binding in group V was the highest among all age groups except for group I, although the differences failed to reach statistical significance. The receptor concentrations (R₀) were comparable among groups except group I which had a slightly increased R₀. The affinity of insulin receptors was the lowest in group I and II, and gradually increased with the age and a positive correlation (p<0.01) was obtained between age and Ke. This increase in affinity with age is considered an adaptive response to the intracellular metabolic derangement often seen in the aged.
No effect of sex on insulin binding was seen before puberty. However, in normal adults insulin binding of the female tended to be lower than that of the male with slightly increased R₀ and decreased affinity in the female. Thus, the slightly decreased binding of the female group was mainly accounted for by the decreased affinity although the differenee in the affinity was not significant.

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Isolated rat pancreatic islets were preincubated in a medium with 16.7mM glucose and incubated with 5.5mM glucose. Both histamine (100μ M) and neurotensin (100nM) stimulated glucagon release from the isolated islets, but not insulin release. The stimulation of glucagon release occurred in the presence of 10 and 100nM neurotensin, while the release of insulin was inhibited in the presence of 1 and 10nM neurotensin. The neurotensin-induced glucagon release was completely inhibited by 1mM metiamide, an histamine H₂-receptor antagonist, added to the incubation medium and not inhibited by 1mM diphenhydramine, an histamine H₁-receptor antagonist.
The results indicate that the histaminergic mechanism, including the H₂-receptor system, may be involved in neurotensin-induced glucagon release from the endocrine pancreas.

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This is a report about a 14-year old girl who, following chemotherapy for malignant teratoma, developed a clinical state of SIADH (syndrome of inappropriate secretion of antidiuretic hormone).
The causative agent was most likely vincristine (VCR). The important feature in this case was that the urinary kallikrein activity was high when she was affected by SIADH and decreased when her hyponatremia improved. Sodium clearance was significantly correlated with the increase in urinary kallikrein activity. It is considered that the kallikrein-kinin system may in part participate in the excessive natriuresis of SIADH.

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The effect of calcitonin (CT) on glycogenolysis in the liver was investigated infasted rats. The fasting produced a marked decrease in the hepatic glycogen content. Thyroparathyroidectomy (TPTX) significantly prevented the decline in hepatic glycogen by fasting as compared with sham operation. This prevention by TPTX wasclearly relieved by the subcutaneous administration of CT (80MRCmU/100g bodyweight). The appreciable effect of the hormone was also observed at the dose of 20 and 40MRCmUCT/100g body weight. The present results suggest that CT plays aphysiological role in the stimulation of hepatic glycogenolysis after fasting in rats.

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Recently we reported that the immature female rat spontaneously expressed twodaily prolactin (PRL) surges; one surge at 1800h (diurnal) and the other at 0600h (nocturnal), but the nocturnal surge ceased occurring as puberty approached. In the present experiment, the effects of ovariectomy and administration of ovarian hormones on the two surges were investigated. Ovariectomy at the age of 23 days did notabolish the two surges occurring on day 29 to 30 and their timing and magnitudewere not different from those in the sham-ovariectomized rat. In the intact femalerat at the ages of 29-30 days, an injection of 2.5μg estradiol benzoate at 1200h progressively elevated PRL levels, whereas 0.5mg progesterone injected at 1200 and 2400h increased the magnitude of diurnal and nocturnal surges. The results indicate that the mechanism for two daily PRL surges in the immature female rat is capable of functioning independently of the ovarian activity, although the latter may exert certain modulatory influence.

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In an attempt to study the influence of vitamin D metabolites on PTH secretion, serum calcium and urinary excretion of cAMP were sequentially measured in conscious perfused rats, and the effects of a single iv injection of the metabolites on these paramenters were examined. Four hours after the administration of 0.25μg/kg (0.6 nmol/kg, probably a physiological dose) of 1α, 25-dihydroxycholecalciferol [1α, 25 (OH) ₂D₃], the urinary excretion of cAMP decreased to a level compatible with that of parathyroidectomized rats (-60% of the initial value; P<0.05) and this level was sustained for nearly 24h. Serum concentrations of calcium (total and ionized) did not change. In parathyroidectomized rats which were continuously infused with bovine PTH (1U/h), the vitamin D metabolite had no significant effect on the urinary excretion of cAMP. 24R, 25-dihydroxcholecalciferol (12.5μg/kg) had no significant effect either on the urinary excretion of cAMP or on serum calcium.
These results suggest that in rats, a physiological dose of 1α, 25 (OH) ₂D₃ inhibits PTH secretion without causing a significant rise iu serum calcium, reflecting a feedback mechanism between active vitamin D metabolite, 1α, 25 (OH) ₂D₃ and the parathyroid glands.

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A patient with Graves' disease who experienced various allergic reactions to both PTU and MMI is reported. She developed fever, skin rash, lymphadenopathy, liver damage and moderate leukopenia during PTU administration. Furthermore, she developed an MMI-induced lupus-like syndrome characterized by generalized lympha denopathy, migrating polyarthritis and myalgia, and results of tests for anti-DNA antibody and anti-nuclear antibody, and LE were positive. All these abnormalities reverted to normal upon discontinuation of medication after subtotal thyroidectomy.

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Studies were undertaken to examine the relationship between serum levels of somatomedin A and its binding sites in the lung and kidney of rats. After three days of fasting, serum levels of somatomedin A decreased, accompanied by increases of 17.5% and 21.4% in binding to the plasma membranes from lung and kidney, respectively. After two days of refeeding, this binding decreased with the increase in the serum level of somatomedin A. There was observed a negative correlation between the serum level of somatomedin A and the percentage of labelled somatomedin A bound to the membranes. These observations suggest that somatomedin down-regulates its own receptor under these conditions. A similar regulatory mechanism was not observed with either hypophysectomized- or GH-treated rats.

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Fifty-one neurons in the ventrolateral part of the medulla oblongata were antidromically activated by electrical stimulation of the suprachiasmatic part of the preoptic area in urethane-anethetized, ovariectomized and estrogen-primed female rats. Two types of antidromic responses were distinguished on the basis of their spike configurations and antidromic spike latencies. One type (“fast spikes”) was characterized by a fast and smooth rising phase and a shorter duration of the initial positive deflection. The othe type (“slow spikes”) had a notch in the rising phase and took a longer time to complete the initial deflection. Mean antidromic spike latency for the fast spikes was 9.8 msec while the value for the slow spikes was 30.2msec. Ionophoretic injection of estradiol was accomplished on 37 of the 51 antidromically identified cells, of which 21 showed slow responses and 16 responded with fast spikes. In cells with slow spikes, estradiol facilitated (n=9) or suppressed (n=3) their generation of action potentials. None of cells with fast responses changed their activity in response to estradiol. It is evident from the present experiment that neurons in the ventrolateral part of the medulla oblongata send their axons directly to the suprachiasmatic part of the preoptic area which plays an important role in the control of the ovulatory surge of LH and that some of these neurons themselves are the sensitive sites of estradiol.

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The concentration of ACTH in extracts of rat anterior pituitary was measured by both radioimmunoassay and bioassay at different stages following adrenalectomy. Both types of ACTH activity decreased the day immediately following adrenalectomy but increased gradually afterwards. Immunological ACTH activity increased to 250% of the control value and biological ACTH activity increased to 490% of control value 3 weeks after adrenalectomy. The increase in biological ACTH activity occurred earlier, and the rate of increase was greater, than that of the immunological ACTH activity.
The distributions of molecular weight forms of ACTH in extracts of anterior pituitary lobes was determined by gel filtration. Three molecular weight forms of immunoassayable ACTH were detected. Biological ACTH activity appeared in the 2nd and the 3rd peaks. A striking change was observed after adrenalectomy in the distribution of biologically active forms of ACTH. The ratio of biological ACTH activity to immunological ACTH activity in each peak changed at various stages after adrenalectomy. This indicated the heterogenous nature of the ACTH included in eachpeak. At 2 and again at 3 weeks, biological activity markedly increased until it exceeded the immunological ACTH activity in the 2nd peak. Dexamethasone had little influence on the elution profile of either immunoassayable and biologically active ACTH in gel filtration. Adrenalectomy may possibly have an effect on the intracellular posttranslational processing of ACTH precursors which leads to the deveploment of biological ACTH activity.

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