In vitro bone culture technique was developed by the modification of the Goldhaber's method. Using this method, pyrophosphate was found to inhibit PTH induced bone resorption as judged by the release of previously incorporated Ca⁴⁵ into the medium and by the histological findings. Furthermore, addition of pyrophosphate markedly enhanced the thyrocalcitonin inhibition of bone resorption in this system. These findings, together with the previous findings that pyrophosphate enhances the hypocalcemic response to TC in vivo, strongly suggest the favorable effect of the combined use of pyrophosphate and TC in the bone diseases characterized by excessive bone resorption.

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A 22 year old male had chronic tetany, hypocalcemia, hyperphosphatemia, short stature, round face, slightly short metacarpals, bone demineralization, elevated alkaline phosphatase, mental retardation, basal ganglia calcification, dental abnormality and bilateral cataracts. Diagnosis of pseudohypoparathyroidism was established through the negative phosphaturic response to exogenous parathyroid hormone. The radiocalcium kinetic analysis indicated normal miscible calcium pool and increased bone formation rate. Radioimmunoassay revealed detectable parathyroid hormone in plasma. Bioassay of thyrocalcitonin in thyroid tissue and peripheral venous plasma gave normal results. Clinical findings of 11 cases of pseudohypoparathyroidism in Japan are also summarized.

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Behavior of multiple hexokinase in the supernatant extracted from alloxan diabetic rat tissues after an insulin administration has been investigated by the DEAEcellulose chromatography. The activity of type II in diabetic liver and muscle, and the activity of type IV in diabetic liver markedly decreased, and by the insulin administration recovered, although the level of type II in muscle did not reach to normal in 24 hrs. after the injection. On the other hand, types I and III were not subject to control by insulin. Hexokinase type I and type II in liver were further purified by the DEAEcellulose chromatography, ammonium sulfate fractionation and hydroxylapatite chromatography, and kinetics and reaction mechanism were studied with these purified enzymes. The initial rate experiments indicated that the insulin insensitive type I showed a different reaction mechanism from the insulin-sensitive type II. The reaction of liver hexokinase type I appears like a ping-pong pathway in which one or more products are released, before all the substrates are added to the enzyme. Type II will be a sequential where ATP and glucose must bind to enzyme before any products are released.

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The response of thyroid weight and iodine metabolism to excess ingestion of iodide was studied in the chick. Treatment of chicks with 1mg of iodide for 4 weeks induced a marked increase in thyroid weight. The radiochromatography of the 131I labelled thyroid hydrolysate showed that a single injection of carrier iodide resulted in a significant but transient reduction of a relative proportion of organic ¹³¹I as well as thyronine ¹³¹I and an elevation of the MIT/DIT ratio. After chronic treatment of chicks with excess iodide, the thyronine ¹³¹I proportion was still decreased notwithstanding the fact that the organic ¹³¹I proportion showed a return to normal and MIT/DIT was rather low. The increased thyroid weight and decreased thyronine proportion returned to normal 9 weeks after termination of the iodide feeding. In the goitrous chicks, the relative proportion of intrathyroidal ¹²⁷I compounds were virtually identical with that of ¹³¹I, although the absolute amount of thyronine ¹²⁷I was increased depending on the increase in total ¹²⁷I content. There was no significant difference in both turnover rate of radiothyroxine and plasma thyronine ¹²⁷I concentration between the goitrous and control chicks. It is suggested that these alterations of iodine metabolism seem to be closely related to the mechanism of goitrogenesis by excess iodide in chicks and may represent an inhibitory effect of iodide on intrathyroidal hormogenesis.

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The rate of 5α-reduction and 17β-dehydrogenation of testosterone added in vitro, the activity of Na⁺, K⁺-insensitive ATPase, and the content of citrate were determined in the ventral prostate of rats of various ages and of castrated animals with and without testosterone replacement therapy.
The rate of 5α-reduction of testosterone changed significantly with aging of the gland, while no significant changes were observed in the rate of 17β-dehydrogenation of testosterone and ATPase activity in all animals used in this experiment. Although the rate of 5α-reduction in the old rat was very low, testosterone treatment increased the rate markedly. Castration caused a significant decrease in the rate of 5α-reduction, and the administration of testosterone restored the rate to the control level. This rate of 5α-reduction recovered to the control level on the 4th day after a testosterone treatment had been started prior to complete growth of the tissue in the castrated animals. These changes of the rate of 5α-reduction proceeded those of the citrate content of the gland.
Physiological significance of 5α-reduction of testosterone in the rat ventral prostate was discussed.

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In order to study the secretory function of growth hormone in puberty and adolescence, fasting serum growth hormone levels and the increase of serum growth hormone levels in response to insulin-induced hypoglycemia were studied by radioimmunoassay in 175 normal individuals aged 10 to 18 yr. It was observed that after the onset of puberty, more cases showed relatively high values of fasting hormone level and more significant responses of growth hormone secretion to insulin-induced hypoglycemia as compared with the values in prepuberty.

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Diurnal periodicity of the hypothalamic content of corticotropin-releasing factor (CRF) was determined in the normal male rat by the intrapituitary microinjection method. It was found that the CRF activity in the rat hypothalamus showed a definite diurnal variation, having the peak value at about 18: 00 and the minimum at 4: 00 or 8: 00 under the lighting regimen of 6: 00 to 19: 00 of day light followed by 11 hrs. of darkness. The close temporal relationship with a definite phase shift observed between CRF activity and plasma corticosterone level appears to support the concept that the diurnal rhythm of the pituitary-adrenal axis is a direct reflection of the rhythmicity of CRF activity in the median eminence of the rat.

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Total and active phosphorylase activities were determined in the rat adenohypophysis before and after stress. It was found that the phosphorylase in this gland existed in two distinct forms and stressful stimuli effectively activated an inactive form of enzyme into an active one, while total activity remained unchanged. The finding may be consistent with the observation that active glycogenolysis ensues on stress in the anterior pituitary tissue.

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Insulin effects on glucose metabolism were studied in normal and diabetic rat tissues. In the epididymal fat pad, diaphragma, and skeletal muscles, glucose-U-¹⁴C up-take from the medium decreases in diabetic rats, and recovers to the normal level with the addition of insulin. Insulin has no significant effect on glucose up-take in both liver and kidney. CO₂ production from glucose-U-¹⁴C decreased in diabetic tissues and not in heart tissue. Insulin causes a significant increases of CO₂ production in the muscles, epididymal fat pad, and diaphragma. The activities of hexokinase and pyruvate kinase decreased in diabetes, and increased with the administration of insulin. In the peripheral tissues, the increase of these enzyme activities via insulin administration would not be caused by the so-called genome units described by Weber et al.(1965), but by a certain factors due to glucose metabolism caused by insulin. Hexokinase and pyruvate kinase exhibit a different pattern of response to insulin according to tissues. These indicates that the presence of multiple enzyme form may be significantly involved.

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An improved pinealectomy in rats has been developed. This operative technique has such advantages as a small cutting area of skull, no injury to the sinuses, slight bleeding and minimum damage to adjacent structures in the brain.

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