In order to study the pathogenesis of reactive hypoglycemia, the responses of plasma glucose, IRI, glucagon immunoreactivity (GI) and total glucagon-like immu-noreactivity (GLI) to 100g oral glucose load were investigated in twenty-six patients of normal weight with reactive hypoglycemia. Of these patients, nineteen exhibited a diabetic OGTT curve. The findings in these patients were compared to normal control subjects (N=20) and to disease-matched patients controls (N=43). The psy- chological status was assessed by Cornell Medical Index Health Questionnaire in most of the subjects, who also received an x ray examination of the upper gastrointestinal tract. In addition, IVGTT was performed in the hypoglycemic patiens. No apparent difference in plasma IRI response to oral glucose was observed between the hypo-glycemic patients and their respective controls. Plasma total GLI concentrations were significantly increased during OGTT in both hypoglycemic groups. Following an oral glucose load, plasma GI levels were suppressed in the hypoglycemic groups to an extent similar to that in the control despite an apparent fall in their plasma glucose levels to the hypoglycemic range in the former. Radiological alterations in the upper gastrointestinal tract; deformity of the duodenal cap, gastric and/or duodenal ulcer, were found more frequently in the hypoglycemic groups. However, no characteristic change in personality was noticed in the patients. During IVGTT, neither plasma glucose nor total GLI level of the hypoglycemics differed from that of each control. The pathogenic factors responsible for reactive hypoglycemia will be discussed.

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The effect of hypophysectomy and bovine growth hormone (GH) administration on somatostatin (SRIF) content as well as gastrin content in the rat stomach was investigated. SRIF content was determined by a specific radioimmunoassay. The total SRIF content in the stomach had decreased 4 weeks after hypophysectomy but was restored significantly in those rats which were subjected to bovine GH administration for 7 days after hypophysectomy. Furthermore, in control rats, an increase in SRIF content in the stomach was observed after 7 days of GH administration. Similar changes in total content of gastrin were observed after hypophysectomy and bovine GH administration, although these changes were not significant. These results indicate that GH may influence gastric function through changes in SRIF and gastrin content in the stomach.

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In order to know the degree of the destruction of peptide hormones in pancreatic tissue of autopsied material, the time courses of the degradation of pancreatic insulin, glucagon and hPP were studied using surgically operated pancreatic pieces kept at room or low temperature. Amounts of insulin, glucagon and hPP in pancreatic tissue were determined by radioimmunoassay. Insulin in the pancreas just after resection was 2.58±0.33U/g (mean±SE). At 3 hrs it decreased to 66.4±3.8%, at 6hrs, to 68.5±5.1% and at 12hrs to 51.7±11.4% of the initial value in the tissues kept at room temperature (20-22°C). When the tissues were kept at 4°C, 90.7±3.9% of insulin at 3hrs, 88.5±7.0% at 6 hrs, and 80.3±2.6% at 12hrs were preserved. 81.3±13.9% of the initial hPP was present in the tissues after 6hrs at room temperature, and it decreased to 20.7±5.7% after 12hrs, whereas no significant decrease in hPP was found even after 12hrs at low temperature. Glucagon content at starting point was 16.85±4.05μg/g and at 3 hrs in the room temperature it fell to 7.46±3.53μg/g (41.5±9.8%) and at 6 and 12hrs only 14.4±4.1% and 5.8±4.2% were left, respectively. At low temperature, at 3hrs 79.3±8.9%, at 6 hrs 62.2±14.7% and at 12hrs 53.5±16.6% was preserved. These findings indicate that special consideration should be taken from the viewpoint of the destruction of hormones in pancreatic tissues obtained at autopsy.

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Rat mammary glands contain cyclic AMP-independent casein kinase and cyclic AMP-dependent histone kinase. The former was easily isolated from cyclic AMPdependent histone kinase by MgCl₂ treatment. Mammary casein kinase was not activated by cyclic nucleotides, and Mg⁺⁺ and ATP were required for activation.
The specific activity of casein kinase in cytosol of rat mammary epithelial cells increased 2 to 3-fold during pregnancy and lactation.
Cytosol of mouse mammary epithelial cells also contained cyclic AMP-independent casein kinase, and the activity of this enzyme was about three times that of the Golgi fraction.

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The correlation between T₄ 5'-deiodinase activity and thyroid hormone concentration in rat tissues was sought. Studies with normal and thyroidectomized rats indicated a significant correlation of the hepatic T₃ concentration with the enzymeactivity in liver homogenate (r=0.80, p<0.01) or in liver microsomes (r=0.08, p<0.01).The correlation between the hepatic T₄ concentration and activity of the enzyme was less significant (r=0.55, p<0.05 for homogenate, and r=0.66, p<0.01 for micrsomes). The degree of T₄ 5'-deiodinase activity in various organs was found to increase in line with tissue concentration of T₃. It seems likely that the level of T₄ 5'-deiodinase activity is controlled by the tissue concentration of T₃.

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Glycosylated T₃ was prepared by binding T₃, a thyroid hormone, to glucose. We identified this compound by thin-layer chromatography and high-pressure liquid chromatography. We also demonstrated that glycosylated T₃ could be separated from T₃ by high-pressure liquid chromatography.

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In order to observe the effect of the adrenergic system on pancreatic glucagon secretion in the isolated perfused rat pancreas, phenylephrine, an αadrenergic agonist, and isoproterenol, a β-adrenergic agonist, were added to the perfused solution. 1.2μM phenylephrine suppressed glucagon secretion at 2.8mM glucose, and it also decreased insulin secretion at 11.1mM glucose. 240nM isoproterenol enhanced glucagon secretion not only at 2.8mM glucose, but also at 11.1mM glucose, as well as insulin secretion at 11.1mM.
In order to study the role of intra-islet noradrenalin, phentolamine, an α-adrenergic antagonist, and propranolol, a β-adrenergic antagonist, were infused with the perfused solution. 10 and 100μM phentolamine caused an increase in insulin secretion, and 25μM propranolol decreased insulin secretion, while they did not cause any change in glucagon secretion.
From these results, it can be concluded that α-stimulation suppresses not only insulin but also glucagon secretion, while β-stimulation stimulates glucagon secretion, as well as insulin secretion. Intra-islet catecholamine may have some effect on the B cell, whereas it seems to have no inffuence on the A cell.

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Administration of steroid hormones evokes a rapid fall in the amount of cytoplasmic receptors in target tissues. This has been considered to be a consequence of the receptor translocation to nuclei, but the physiological significane of depletion of the cytoplasmic receptors after hormone administration has not been fully elucidated. In the present study, depletion and replenishment of the cytoplasmic glucocorticoid receptor in rat tissues were examined after the administration of glucocorticoids of different biological potencies. Dose dependent depletion was observed in all tissues examined and doses required for complete depletion of the receptor were correlated with biological potencies of steroid administered. The receptor in the heart and the skeletal muscle was relatively sensitive to hormone injection while more than 4 times the amount of steroids was required to induce a similar effect in the thymus and the spleen. The duration of the period of depletion of the receptor in cytosols was also dose dependent and correlated to the biological potency of steroid administered. Replenishment took place earlier in the thymus and the spleen than in the heart and the skeletal muscle. Significantly lower binding affinity was observed in the replenished receptors. The administration of cycloheximide in a dose which inhibits more than 95% of³H-leucine incorporation did not influence either the depletion or the replenishment of the receptor induced by hormone injection. In conclusion, depletion and replenishment of the cytoplasmic glucocorticoid receptor appeared to be closely correlated to the physiological action of hormones.

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Polyamine content in testes of various vertebrates was studied extensively. Putrescine, spermidine and spermine were detected in all the animals examined, although the distribution pattern varied greatly from animal to animal. Cadaverine was detected only in amphibian testes; sym-homospermidine was found not only in testes but also in various other tissues of amphibians and of some reptiles.
In the newt testis the concentration of cadaverine was lower than that of any other polyamines in summer, but there was a great increase in cadaverine content from autumn to winter. The testicular content of cadaverine was greater than that of other polyamines in winter. There was a gradual decrease in the cadaverine content in spring. The spermidine and spermine levels, which were rather low in winter, increased in spring and reached a peak in summer when spermatogenesis was active. The testicular concentration of putrescine that was much higher than that of spermidine or spermine throughout the year, increased only a little in summer. There was a significant negative correlation between the cadaverine levels and four other polyamine levels. Exogenous cadaverine decreased the testicular levels of putrescine. Mammalian gonadotropins decreased the cadaverine levels and increased the levels of other polyamines. A partially purified LH fraction from pituitaries of bullfrog, Rana catesbeiana, was also potent in depleting cadaverine of the testes of newts kept at 8°C. These results suggest that testicular cadaverine suppresses the biosynthesis of polyamines, especially spermidine and spermine which are closely associated with spermatogenesis.

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The effect of TRH in vitro was observed on electromyograms and isometric tension changes in the uterine horn isolated from the rat. TRH induced transient prolongation of the duration of spike bursts in the electromyogram and an increased tension in contraction of diestrous uterine horns. No distinct response to TRH was elicited in preparations from rats during other estrous stages. TRH produced a contraction associated with a burst of spike potentials in the quiescent horn from the estrogenprimed ovariectomized rat. Priming with progesterone was not a prerequisite for responsiveness to TRH. In a medium with a high Ca concentration, diestrous uteri were quiescent but a transient contraction associated with a burst of spike potentials was induced by TRH. In a Ca-free medium, TRH failed to elicit any response in the diestrous uterus but acetylcholine induced a contraction without associated spike potentials. It appears that TRH stimulates Ca-influx into the uterine muscle in which responsiveness is dependent on estrogen priming.

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The effect of prolactin on the secretions of dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) as well as that of cortisol were studied in vitro in order to investigate the possible regulatory role of prolactin on steroidogenesis of the human fetal adrenal at mid-gestational age. The addition of 0.5μg/ml of human prolactin to the incubation medium produced a significant (P<0.05) increase in DHEA, DHEAS, and cortisol secretion. These results indicate that prolactin has a regulatory role in steroidogenesis in the human fetal adrenal at mid-gestation.

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Changes in the pituitary-thyroid axis in patients with Hashimoto's thyroiditis following withdrawal of thyroid suppressive therapy were analyzed. The group of patients with thyroid adenoma served as control (group I). Patients with Hashimoto's thyroiditis were divided into 2 groups on the basis of serum TSH levels 8 weeks after discontinuing the exogenous throid hormone (group II, less than 10μU/ml; group III, more than 10μU/ml).
During treatment with L-T₄ (200μg/day) or L-T₃ (50μg/day), there was no significant difference in serum T₄-I and T₃ levels among the three groups. Following L-T₄ withdrawal, basal serum TSH levels were higher at 2 to 8 weeks in groups II and III than in group I. Serum TSH response to TRH was greater at 4 to 8 weeks in groups II and III than in group I. Following L-T₃ withdrawal, basal serum TSH levels were higher at 1 and 2 weeks in group II than in group I, while those of group III were consistently higher during the study. Higher TSH responses to TRH were observed at 1 to 8 weeks in groups II and III. Neither basal nor TRH-induced prolactin (PRL) secretion differed significantly among the three groups.
We have demonstrated that pituitary TSH secretion in patients with Hashimoto's thyroiditis is affected more by withdrawal of thyroid hormone therapy than in patients with thyroid adenoma. In addition, the present findings suggest a difference between the sensitivity of thyrotrophs and lactotrophs in Hashimoto's thyroiditis after prolonged thyroid therapy is discontinued.

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The seasonal variation in pituitary gonadotropin in the adult male newt, Cynops pyrrhogaster pyrrhogaster was investigated by means of isoelectric focusing (IEF) coupled with radioreceptor assay (RRA), which employed Anolis or Xenopus testicular homogenates as receptors and ¹²⁵I-rat FSH as radioligand. In the Anolis RRA system, the standard curve was obtained with 0.125-16 ng/tube of NIAMDD rat FSH I-3. Purified preparations, chicken LH IEF-1, chicken FSH AGCHD11113A and bullfrog basic gonadotropin-IV competitively inhibited the binding of the radioligand, but NIAMDD rat LH I-4 and human chorionic gonadotropin did not crossreact. The autoradiographic study revealed that ¹²⁵I-rat FSH bound to the constituent cells of the seminiferous tubules in the Anolis testis, but scarcely to Leydig cells. In the IEF pattern of gonadotropin in February obtained by Anolis RRA, distinct peaks were observed at pH 9.05 (component B) and 8.55 (component C), and less distinct peaks were observed at pH 9.80 (component A), 7.55 (component D) and 7.05 (component E). When the same fractions were assayed by Xenopus RRA, five components were found in the alkaline region, which corresponded to those observed with Anolis RRA. Similar results were obtained with pituitary extracts in May. In July, the IEF pattern obtained by Anolis RRA indicated two additional components at pH 6.30 (component F) and 5.27 (component G) in the acidic region, which were not found by Xenopus RRA. The relationship between the testicular function and the nature of pituitary gonadotropin in the reproductive cycle was discussed.

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The receptor binding activity (R) and immunoreactivity (I) of serum and pituitary FSH were measured in normal, gonadectomized, and gonadal steroid-treated rats of both sexes employing radioreceptor assay and radioimmunoassay, respectively, and R/I ratios were analyzed. At 11 weeks of age, R/I ratios of serum and pituitary FSH were significantly higher in normal females than in males. From 11 to 13weeks of age, the ratios of both FSH further increased in females, while in males, the ratio of serum FSH decreased and that of pituitary FSH increased. Orchiectomy caused an increase in the ratio of serum FSH, while ovariectomy caused a decrease, so the ratios in the gonadectomized animals of both sexes became almost equal, suggesting the secretion of a gonadectomy type FSH in these animals. Both testosterone propionate (TP) and estradiol benzoate (EB) treatments decreased the ratios of serum FSH in gonadectomized rats. However, TP and EB had an effect opposite on the ratio of pituitary FSH in these rats, i.e. TP caused a decrease, while EB caused an increase. This effect was more obvious in females than in males. These observations indicated that the presence and absence of the gonads, and the gonadal steroids influence not only the quantity but also the quality of FSH. The changes in the quality of the hormone are discussed in relation to its multiplicity.

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A 24-yr-old woman with hypertension, hypokalemic alkalosis, low plasma renin and hypoaldosteronism was studied. Plasma aldosterone, renin and potassium returned to normal and blood pressure fell after sodium restriction or the administrationof triamterene. Thiazide therapy also normalized her blood pressure while dexamethasone, spironolactone and furosemide did not improve her symptoms. Plasma aldosterone levels were low and responded poorly to a short term ACTH injection, but responded well to the maximal adrenal stimulation by ACTH-Z. Plasma levels of cortisol, corticosterone and deoxycorticosterone were within the normal range. Adrenalscintigram with ¹³¹I-adosterol and abdominal computed axial tomography did not reveal the presence of a sizeable adrenal tumor. In addition, the urinary kallikrein excretion was low after sodium restriction and showed no response to saline infusion. These findings suggest that the excessive secretion of unusual mineralocorticoids may not exist in this case. From these observations and the results of the therapeutic responses to the diuretic agents, we conclude that the primary cause of the disorder of this patient seems to be a renal defect in the distal tuble in handlingsodium and potassium which is similar to that in Liddle's syndrome.

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Maffucci's syndrome (association of multiple enchondromatosis and multiple hemangiomata) is rarely associated with other ectodermal tumors. The present case is the second in literature in which the Maffucci's syndrome is associated with the parathyroid adenoma resulting in primary hyperparathyroidism. Although the cystic lesions of the bone and the ectopic calcifications are common to both diseases, pathogenesis apparently not related. The association of parathyroid adenoma with Maffucci's syndrome suggests the potential involvement of mesenchymal organs in this ectodermal neoplastic disorder.

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Species specificity of the radioreceptor assay (RRA) for rat FSH, in which pregnant mare serum gonadotropin (PMSG)-treated immature rat ovary was employed as the receptor, was compared with that of NIAMDD rat FSH radioimmunoassay (RIA). In the RIA system, pituitary preparations from mammals only showed significant crossreaction. Their inhibition curves, however, were not always parallel to the standard curve. On the other hand, in the RRA system, the pituitary preparations from mammals, avians, lizard and amphibians competitively inhibited the binding of radioactive rat FSH to the ovarian receptor. Only the pituitary preparation from dog salmon failed to show any crossreaction in the RRA system. These results indicated that this RRA system would be useful for the measurement of FSH or gonadotropins of the pituitaries from mammals to amphibians.

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