To clarify the insulin-releasing mechanism, we studied insulin release and the efflux of [³²P] phosphate by glucose at 0.1mM/min of gradient level or at 16.7mM, and other metabolism in islets of rat Langerhans.
When treated with 1mM iodoacetic acid (IAA) plus the anomers of D-glucose at2.8mM for6min at 37°C, islets elicited insulin at half the control rate under the step-wise stimulation by glucose and at the same rate as the control under the slow-rise stimulation by glucose. Using islets treated with IAA plus the α anomer at 16.7mM, the step-wise stimulation secreted insulin at half a rate of the control and the slow-rise stimulation at the rate lower than the control, which was not significantly different from the control rate. Treatment with IAA plus the β anomer at 16.7mM inhibited insulin release under both types of stimulations by glucose. The step-wise stimulation caused the same rapid efflux of [³²P] phosphate from IAA treated islets as from the control islets, except for islets treated with IAA plus the β anomer at 16.7mM. The rate of glucose utilization in islets was inhibited by all IAA-treatments to the same extent, being merely half the control rate. Treatments with IAA plus the anomers at 16.7mM significantly reduced the formation of [³H]-cAMP and the activity of protein phosphokinase in islets, while in the presence of the anomers at 2.8mM IAA produced no significant effect. Neither IAA-treatments altered the uptake of ⁴⁵Ca and the ATP content in islets. The uptake of [¹⁴C] IAA was significantly enhanced by the presence of the β anomer at 16.7mM to two times the control level.
On the basis of these results, we suggested that the B cell might contain both glucoreceptors and rate-sensors of glucose controlling insulin release and the former might be less sensitive to IAA as compared with the latter.

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With dopamine (0.5μg/kg/min) infusion into the renal artery of thyroparathyroidectomized dogs, urine output and inorganic phosphate excretion increased significantly (p<0.05), but the increase in sodium excretion was low and not statistically significant. However, natriuresis and phosphaturia due to the infusion of dopamine were accelerated more markedly by the pretreatment with phenoxybenzamine. Dopamine was infused into the renal artery in doses too small to affect renal hemodynamics (0.02-0.05μg/kg/min) after the treatment with phenoxybenzamine and alprenolol with the result that phosphate and sodium excretion increased significantly (p<0.05). The excretion rate of cAMP did not change. This suggests that the effect of dopamine on sodium and phosphate excretion is directly influenced by alpha adrenergic activity in the kidney. The mechanism of natriuresis and phosphaturia by dopamine is, however, independent of changes in parathyroid hormone and the adenyl cyclase-cAMP system.

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Serial oral glucose tolerance tests in rats treated with streptozotocin and nicotinamide showed that blood glucose levels after glucose loading were suppressed significantly 7 months after treatment as compared to those of earlier stages. Postglucose plasma insulin levels were significantly elevated at the 9th to 12th month and concomitantly fasting plasma glucagon levels rose significantly. At that time pancreatic islet cell tumors were demonstrated in all of the rats in this experiment. Post-glucose plasma glucagon levels, however, did not show remarkable changes throughout the observation.
In spite of hyperinsulinemia, post-glucose plasma glucagon levels of tumorbearing rats were significantly lower than those of body weight adjusted controls.
It is inferred from the study that secretory activity of pancreatic A-cells of tumorbearing rats is restrained by excess insulin released from islet cell tumors.

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Effects of preparations of saponin mixture and isolated ginsenosides, extracted from the root of Panax ginseng, on plasma corticotropin (ACTH) and corticosterone concentrations in rats were determined by the radioimmunoassay and competitive protein binding method. When ginseng saponin mixture was administered to rats intraperitoneally, plasma ACTH and corticosterone increased significantly 30, 60 and 90 min after the treatment. The kinetic pattern of the increase in plasma ACTH was almost parallel to that in plasma corticosterone. Isolated ginsenoside, protopanaxadiol or protopanaxatriol glycoside, also increased plasma corticosterone. The ginseng-induced increase in plasma corticosterone was suppressed by pretreatment with dexamethasone. Thus the ginseng saponin was found to act on the hypothalamus and/or hypophysis primarily, and stimulated ACTH secretion which resulted in increased synthesis of corticosterone in the adrenal cortex.

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¹²⁵I-somatomedin A (SMA) was injected iv into rats. Distribution studies in rats showed concentrations of radioactivity to be high in kidney and plasma, low in brain, and intermediate in other tissues. The concentration of total and trichloracetic acid (TCA) precipitable radioactivity in rat blood and tissues fell at rapid rate. Ninety per cent of the radioactivity was in the urine in 24hr, and only 15% of urine radioactivity was TCA precipitable. The half-life of the radioactivity in TCAprecipitable fraction from blood and that from tissues were nearly identical (about 6hr). In both liver and kidney, TCA-precipitable radioactivity was detected in membrane and/or organellar fraction and cytosol fraction. Sephadex G-200 chromatography at neutral pH of plasma after injection of¹²⁵I-SMA revealed3peaks of radioactivity in higher molecular weight region than purified SMA.

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Effects of ergocornine and reserpine on tail resorption during metamorphosis Bufo bufom japonicus tadpoles were studied. At prometamorphosis, ergocornine induced precocious tail resorption, while reserpine scarcely affected the tail size. At the climax of metamorphosis, ergocornine was almost ineffective in accelerating tail resorption, while reserpine was effective in inhibiting tail resorption. Since prolactinlike hormone is known to block the tail resorption induced by thyroid hormones, was postulated that the release of the hormone is blocked by ergocornine during prometamorphosis and stimulated by reserpine during climax.

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Binding of ³H-dexamethasone (Dex)-rat liver cytoplasmic receptor complex to nuclei from fetal rat livers in vitro exhibited a high-affinity and saturable nature (Kd=1.5×10^-M, maximal binding sites=470 fmole/mg DNA), and the binding was inhibited competitively by prior injection of Dex in vivo. While binding of ³H-Dex-receptor complex to nuclei from adult rat liver was in low affinity and unsaturable, and injection of Dex prior to the sacrifice of animals did not influence the nuclear binding to ³H Dex-receptor complex in vitro. Differential salt-extraction with KCl solution of the nuclear bound³H-Dex receptor complex revealed the presence of salt-extractable and residual forms of bound receptors. The amount of the fraction extracted with 0.3M KCl reached its maximum at 10min after the start of incubation, while the 1.0M KClextractable and residual fractions reached their maximum plateaus after 30min of the incubation. Scatchard analysis revealed that the binding of the receptor complex to the 0.3M and 1.0M KCl fractions was saturable, while the residual fraction did not show any tendency of saturation under the experimental conditions employed in the present study. The results obtained in this work were compared to those which have been reported by other investigators.

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A practical method was developed for enzyme-immunoassay of serum estriol, with alkaline-phosphatase as a marker enzyme.
Alkaline-phosphatase was conjugated with estriol-6-(O-carboxymethyl) oxime using water soluble carbodiimide. The estriol-alkaline-phosphatase complex, which has both enzyme activity and capacity to bind anti-estriol serum, was obtained by Sephadex G-200gel filtration. This complex, which was stable for at least 3 months at 4°C, was used as enzyme-labelled estriol.
Anti-estriol serum raised against estriol-6-(O-carboxymethyl) oxime bovine serum albumin was employed.
“Bound and free” estriol were separated by the double antibody method.
A linear relation was obtained between estriol concentration and antibody-bound alkaline-phosphatase activity in the range of 0.2-100ng estriol/ml.
In this assay system, cross-reactivity with other steroids was negligible under physiological conditions, and endogenous alkaline-phosphatase, which increases during the late pregnancy, caused no interference.
The coefficients of variation were 3.3-14.2%(within assays), and less than 22%(between assays), and the mean recovery rate was 77.5%.
Serum estriol values determined by the present method correlated well with those determined by radioimmunoassay (r=0.90for total estriol r=0.98 for free estriol).
The present method of enzyme-immunoassay is suitable for measurement of serum estriol during pregnancy.

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A 22 year old man with two extra-adrenal pheochromocytomas located in the media stinum and in the pelvis is presented. We believe this is the first report in Japan of extra-adrenal multiple pheochromocytomas in adult located in the two distant places.

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The ATPase preparations from the hog thyroid was preincubated with various amounts of trypsin. The activity of Mg-ATPase was consistently elevated. On the contrary, the Na, K-ATPase activity decreased with increasing amounts of trypsin. The effects were similar to those which were observed in the enzyme preparations treated with basic polyamino acids as previously reported. This phenomenon seemed to be specific in the preparations from the thyroid.
The Mg-dependent activity was increased after pretreatment with trypsin or poly-L-lysine (PLL) when CTP, ITP and UTP were used as substrate. Thus the substrate specificity of Mg-ATPase was low.
The enzyme-kinetics using ATP as substrate showed that the increase in activity was due to an increase in Vmax and not to a change in Km.
The activity of Mg-ATPase was increased even after30min of preincubation with trypsin, while the Na, K-ATPase activity was almost diminished.
These results suggest that the activity of Mg-ATPase in the preparation from the thyroid is specifically changed by the modification of the molecular environment of the enzyme with trypsin or basic polyamino acids.

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After gel chromatography of human and rat serum at pH7.4, all endogenous somatomedin A was recovered in the high molecular weight range. The largest peak was found in the γ-globulin (II) region and the next largest peak found in the albumin region (III). The amounts of somatomedin A in the peak II region increased in serum from acromegalies and decreased in serum from growth hormone deficient patients.
Four radioactive peaks were observed after gel chromatography of serum incubated with ¹²⁵I-somatomedin A. Only the two peaks corresponding to peaks II and III out of the four peaks were displaced by adding 50μg of partially purified cold somatomedin A. The radioactivity of peak II decreased in sera from growth hormone deficient patients and increased after growth hormone administration.
These observations support the hypothesis that the growth hormone regulates not only somatomedin A but also its carrier protein.

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The effects of intracerebroventricular administrations of three natural angiotensins, angiotensin I (ANG I 3.8×10^-11-9.4×10^-10mol/kg body weight), II (9.6×10^-12-2.4×10^-10mol/kg body weight) and III (2.7×10^-10-2.5×10^-9mol/kg body weight) on systemic blood pressure were investigated in conscious rats. Angiotensin II (ANG II), ANG I and angiotensin III (ANG III), increased blood pressure in a doserelated manner. The order of potency of angiotensins was ANG II>ANG I>ANG III. The intraventricular administration of a converting enzyme inhibitor (SQ 14225, 6.9×10^-8mol/kg) abolished the central effect of ANG I, while an angiotensin II analogue ([Sar¹-Ala⁸] ANG II, 1.1×10^-8mol/kg) administered intraventricularly inhibited the central pressor effects of these three angiotensins. These results suggest that ANG II is a main mediator of the renin-angiotensin system in the central nervous system.

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Plasma thyrotropin (TSH) and cortisol concentrations were suppressed immediatelyafter an intravenous bolus dose of8mg betamethasone in 6 male subjects. The circadian variations of these hormones disappeared for40hr (TSH) and44hr (cortisol). Plasma thyroxine (T₄), 3, 5, 3'-triiodothyronine (T₃), 3, 3', 5'-triiodothyronine (reverse T₃) levels did not show diurnal variations before betamethasone administration. Plasma T₃levels decreased to 66% of the basal levels 20hr after batamethasone administration, whereas plasma reverse T₃levels increased to163% of the basal levels at 24hr. These changes were reversed by3to5days after betamethasone. Theearlier recovery of the diurnal rhythm of TSH than that of cortisolsuggests thatthe TSH rhythm is not under the direct control of circulating cortisol.

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The effects of the prostaglandin F_2α (PGF_2α) given into the third cerebral ventricle on the unit activity of neurosecretory neurones in the paraventricular nucleus (PVN) were studied in urethane-anesthetized rats. The firing activity of PVN neurones was recorded extracellularly and 50 neurones were antidromically identified as neurosecretory neurones. Thirty of them were classified oxytocinergic neurones because they gave a burst of action potential 12-15 sec before reflex milkejection and the remaining twenty PVN neurones which showed no response prior toreflex milk ejections were regarded as non-oxytocinergic ones.
Twenty-five (83%) of the 30 oxytocinergic neurones increased in the firing rate following the intraventricular (IVT) injection of PGF_2α (500ng in 1μl of isotonic saline) and the responses lasted for about 20-30min. The remaining 5 (17%) oxytocinergic neurones showed no response in the firing rate to IVT PGF_2α. Fifteen (75%) of the20nonoxytocinergic neurones decreased in the firing activity in response to IVT PGF_2α, and the remaining 5 (25%) of them showed no response. IVT injection of isotonic saline (1μEl) did not affect the firing activityof both the oxytocinergic and nonoxytocinergic cells. The intramammary pressure was slightly increased by the IVT administration of PGF_2α.
These findings indicate that IVT PGF_2α has a differential action on oxytocinergic and non-oxytocinergic neurones in rats.

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Serum levels of L-thyroxine (T₄) and L-triiodothyronine (T₃) of the masu salmon, Oncorhynchus masou, were measured by radioimmunoassay during the months from March to September. Serum levels of T₄ and T₃varied from0.06to1.44μg and from0.06to0.35μg per100ml serum respectively, although T₄content could not be detected in some specimens.
T₄ level showed a seasonal fluctuation in which a higher value was observed in April when parr-smolt transformation was proceeding. T4 level in spring, particularly in April and June, was significantly higher in smolt than in parr.
T₃ content showed a small variation during the observed monthsand did not increase at smoltification, although the content tended to decrease to a minimum level in September when T₄ level showed also the lowest level.

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Ginseng saponin administered intraperitoneally to rats induced a significant rise in plasma corticosterone, while it tended to increase plasma glucose and to decrease plasma immunoreactive insulin. Oral or intraperitoneal administration of ginseng saponin increased plasma corticosterone in unanesthetized, pentobarbital-anesthetized or alloxan-diabetes rats. The histamine-induced rise in plasma corticosterone was suppressed by pretreatment with diphenhydramine, whereas the ginseng-induced rise was not. Ginseng saponin decreased rectal temperature while it increased plasma corticosterone. Ginseng-induced corticosterone secretion was superimposed on the basal levels of plasma corticosterone due to fasting and circadian rhythm. Thus ginseng saponin would be a kind of stressful agent and have different features associated with the stimulation of the pituitary-adrenocortical system from several other chemical agents.

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The effect of pentagastrin on the pituitary-adrenocortical secretion was examined in male rats. In the morning the intraperitoneal injection of this peptide produced a slight, but significant, decrease in the plasma corticosterone levels, but it had no effect on the evening rise due to circadian periodicity and the stress-induced elevation of the plasma corticosterone level. Following intracerebroventricular administration of pentagastrin, plasma corticosterone tended to decrease and in in vitro incubation of rat pituitary tissue the addition of pentagastrin elicited a suppressive effect on the ACTH release from the tissue into the medium. It was suggested that gastrinlike peptide might control the secretion of ACTH.

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Under constant experimental conditions of room temperature and illumination, a highly significant seasonal difference was observed in the mortality rate of rats which received hydrocortisone on the first day of life. The rate was high in winter and low in summer. Inborn circannual variation of the susceptibility to exogenous corticosteroid was shown to exist in newborn rats.

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The blood flow of thyroid, adrenal cortex and renal cortex in the pentobarbital anesthetized rat was assessed from hydrogen gas desaturation curve. The microcirculation of thyroid was markedly augmented within 2 min after an intraventricular injection of Thyrotropin-Releasing Hormone (TRH) while Met-Enkephalin (ENK) failed to influence. Both TRH and ENK stimulated the microcirculation of adrenal cortex moderately. ENK diminished the microcirculation of renal cortex whereas TRH did not exert any effect. The response of thyroid to TRH was abolished by vagotomy, thus the existence of a specific TRH-vagus-thyroid connection was indicated.

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