From 1955 to 1963, 159 cases of Grave's disease were treated with antithyroid drugs for more than 6 months. This report concerns the outcome of these cases in 1969. Among 159 patients treated with antithyroid drugs, the present status could be studied in 86 cases. In these 86 cases, 24 were in remission for more than 2 years after the discontinuance of antithyroid drug therapy, 4 were in remission less than 2 years after the discontinuance of antithyroid drug therapy, 1 case was still hyperthyroid, 9 cases were still receiving antithyroid drugs, 6 underwent an operation because of recurrence, and 24 underwent 131t therapy because of recurrence. Remission rate after the administration of antithyroid drug for less than one year was 24%. In recurrent cases after further administration for 2 to 6 years, 10-20% of the patients experienced prolonged remission. In order to find out the factors related to permanent remission, 42 patients with permanent remission and 40 patients who failed permanent remission were compared in several factors.
From these studies, the incidence of permanent remission seems to be high in the following cases. 1) small goiter 2) short duration of symptoms 3) reduction in the size of the goiter during the treatment 4) positive suppression by thyroid suppression test at the conclusion of treatment. It was also observed that in cases in which antithyroid drug therapy was not effective after one year, further treatment for 2 to 5 years led to permanent remission in some cases. However, such a possibility is very small after more than 6 years of treatment.
The authors have 9 patients who have been taking small doses of antithyroid drugs for 5 to 12 years and working well in euthyroid conditions. Considering the shortcomings of surgery and ¹³¹I therapy, this kind of treatment might be appropriate in some cases.

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The presence of a luteinizing hormone inhibitor in the urine of albino rats was demonstrated. This inhibitor is a heat-stable, non-dialyzable, acid-precipitable and celiteabsorptive substance.

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Effects of glycyrrhizin, an active principle of liquorice, on cholesterol metabolism, and its correlation with cortisone action were investigated using adrenalectomized rats.(1) Incorporation of acetate-1-¹⁴C and mevalonate-5-³H into cholesterol of liver slices was greatly stimulated by glycyrrhizin pretreatment, i. e., 1-10mg esp. 1mg per 100g body weight per day intramuscularly for 5 days. Combined administration of glycyrrhizin with cortisone even weakened the stimulatory action of glycyrrhizin, although cortisone itself had a stimulatory action on cholesterogenesis.(2) Direct addition of glycyrrhizin in vitro to the incubation media containing liver slices of normal rats also increased cholesterogenesis at the concentration of 10^-5-10^-3M.(3) Excretion of intravenously injected cholesterol-4-¹⁴C into bile of bile duct-cannulated rats was much accelerated by glycyrrhizin pretreatment, 2mg per 100g body weight per day intramuscularly for 5 days. Rates of increase of radioactivities excreted into bile by glycyrrhizin pretreatment were 4.5 times, taurocholic acid; 2.8 times, taurochenodeoxycholic acid; 2.7 times, cholesterol; and 3.7 times, total ¹⁴C, respectively.(4) Fecal excretion of intraperitoneally injected cholesterol-4-¹⁴C was also stimulated by glycyrrhizin pretreatment. Total ¹⁴C and total bile acids-14C were increased up to about 2 times, while non-saponifiable materials-¹⁴C and 3β-OH-sterols-¹⁴C remained within 1.5 times.(5) Elimination of intravenously injected cholesterol-4-¹⁴C from plasma was accelerated by glycyrrhizin injection.(6) Glycyrrhizin treatment reduced plasma cholesterol and triglycerides levels of cholesterol diet fed rats.

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As a fundamental experiment for the study on the role of growth hormone in mouse mammary gland, some immunological properties of rabbit antiserum to mouse growth hormone (MGH) were studied.
Antiserum was obtained by immunizing New Zealand White male rabbits with MGH preparation extracted from mouse anterior pituitaries. The precipitin titer of the antiserum by precipitin ring test against MGH preparation was 1: 16. The antiserum did not react with mouse serum, and extracts of brain, liver, kidney, spleen and heart. The immunoelectrophoretic pattern of polyacrylamide gel after electrophoresis of anterior pituitary with the antiserum or the reaction of antiserum with MGH and mouse prolactin (MPL) preparations on the Ouchterlony agar plate showed two precipitin arcs or lines; one appeared to be due to MGH and another due to MPL. The absorption of the antiserum with MPL preparation resulted in the development of a single precipitin line between the absorbed antiserum and MGH preparation on the Ouchterlony agar plate. Further, immunoelectrophoretic pattern of polyacrylamide gel after electrophoresis of mouse pituitary homogenate with the absorbed antiserum showed one precipitin arc at the corresponding site of MGH band. Inhibition by the antiserum of the biological activity of MGH was proven in rat tibia test and in body and mammary growth of a mouse.
All the results have demonstrated that the antiserum absorbed with MPL preparation is specific only to MGH.

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Parathyroid cysts were produced in rats by excessive doses of dihydrotachysterol.(DHT) and calcium acetate. Although overdoses of each DHT, calcium or their combination are believed to suppress the activity of the parathyroid cell, the present electron microscopic observation showed signs of enhanced protein synthesis and secretion of the cells in all stages of cyst formation. It seems reasonable to assume that this cyst formation depends upon two main processes: retention of secretory material in the intercellular spaces and liquefaction necrosis of the paratkyroid cells which emerges in rather later stages of cyst formation.

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Short-(3.5hr) and long-term (3 days) effects of ACTH in vivo on the incorporation of ³H-leucine into cell fractions from rat adrenal glands were examined, with special regard to effects of the hormone on the rate of the amino acid incorporation into submitochondrial fractions. An injection of ACTH caused a significant increase in the rate of the radioactive amino acid incorporation into the inner membrane and soluble matrix fractions of adrenal mitochondria within 3.5 hr while no significant effect of ACTH administration was observed in the other subcellular fractions. Injections of ACTH for consecutive 3 days resulted in the elevated rate of the incorporation into all subcellular fractions except into the acid-soluble fraction. Physiological significance of the results obtained was discussed with respect to the steroidogenic effect of ACTH.

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The relationship between the changes of plasma free fatty acids (FFA) and human growth hormone (HGH) levels was investigated in normal young male subjects.
The administration of nicotinic acid with its concomitant lowering of plasma FFA was followed by a rise of plasma HGH. The HGH rise could be inhibited by the simultaneous administration of heparin which prevented the fall of plasma FFA, or by glucose administration. The administration of heparin alone resulted in an increase of plasma HGH also in association with the fall of plasma FFA in the absence of any changes in plasma glucose levels. The rise of plasma HGH failed to occur when plasma FFA was kept elevated or when glucose was given.
From these results, it was suggested that the fall of plasma FFA has a stimulatory effect and in turn, the elevated plasma FFA has an inhibitory effect on HGH secretion.

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Effects of repeated injections of various doses of L-thyroxine (T₄) on ¹⁴C-leucine incorporation into anterior pituitary proteins of thyroidectomized rats were studied. The normal level of protein-bound iodine (PBI) was maintained by a replacement dose of 0.8μg T₄ per 100g body weight per day. Thyroidectomy resulted in a slight increase in ¹⁴C-leucine incorporation into total pituitary protein. The increased ¹⁴C-leucine incorporation was not suppressed by lower doses of T₄ but rather a slight increase was observed. At 2μg dosis or higher doses the T₄ suppression was remarkable. Twenty, μg dose of T₄ reduced the incorporation below the normal level. There was a significant negative correlation between the rate of ¹⁴C-leucine incorporation and PBI values. Disc electrophoresis study revealed that synthesis of growth hormone (GH) decreased significantly after thyroidectomy and this decreased GH synthesis was normalized by repeated injections of 0.8μg of T₄. Injections of 20μg of T₄ caused no further increase in GH synthesis. Synthesis of prolactin was also diminished by thyroidectomy and restored to normal by T₄ supplement. The interrelation between thyroid states and synthesis of anterior pituitary proteins was discussed with special reference to the pituitary-thyroid axis.

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Adult proestrus rats were prevented from ovulating by injection of chlorpromazine (CPZ) between 11: 30 AM and 11: 45 AM. At 3: 00 PM on the same day CPZ-blocked females were injected intravenously with follicle stimulating hormone (NIHFSH-S5) and/or luteinizing hormone (NIHLH-B6). Data from these studies demonstrate a synergistic action between FSH and LH resulting in ovulation. Evidence for synergism was based on the observation that the incidence of ovulation produced by various combinations of the gonadotropins was in general greater than when either one was administered alone.

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Plasma prolactin concentration of serial blood samples taken from cows and goats bearing indwelling jugular venous catheter was assayed by a radioimmunologic procedure. Using 9 lactating cows, the response of prolactin release to milking was investigated at different stages of lactation. In all cases, plasma prolactin levels rapidly increased and reached a peak 4-20 min after the start of milking. The magnitude of the response was considerably different with the stage of lactation in the same cow. The peak of plasma prolactin released by milking was highest in the early stage of lactation (189±34ng/ml, SE), and decreased thereafter with the advance of lactation. Conspicuous response of prolactin release with a 40-to 100-told increase by milking was also obtained in the lactating goats. Feeding could induce a rapid elevation of plasma prolactin in the lactating cow. Mimic-or sham-milking in heifers and in virgin goats in which teats were pulled and the udder was massaged by hands for 5 min, induced an acute prolactin release within 2 min after the start of stimulation, although there was no milk flow. Stressful stimulus associated with venipuncture also elevated the plasma prolactin in the lactating and non-lactating animals. These findings lead to the conclusion that prolactin is a hormone which can be released by various stimuli and that milking is the most powerful of the stimuli for the acute prolactin discharge from the anterior pituitary gland in the cow as well as in the goat at least in the early stage of lactation. At the same time, a variety of non-specific stimuli can also cause a rapid rise in plasma prolactin concentration.

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The removal of the seminal vesicle in 4-week-old, 6-week-old or 1.2-year-old rats resulted in a significant increase in the weight of the lateral prostate 6 weeks later examined. The weight change was mainly due to a marked distension of alveoli but showing close resemblance to structures of the control animals with secretory activity. RNA/DNA ratio in the unit tissue increased. Constricted alveoli and epithelial hyperplasia in many alveoli were demonstrated after removal of the seminal vesicle only in the lateral prostate of aged rats, though a less marked change: in the weight was shown. The degree of the hypertrophy of the prostates was largely dependent on the age of rats. The greatest increase in the weight of both lateral and ventral prostatic lobes was observed when the seminal vesicle was removed at 4 weeks of age. More than one hundred per cent, 94% and 48 % increase in the weight of the lateral prostate over the control values were shown in immature, young adult and aged rats respectively. The weight of the ventral prostate also increased after removal of the seminal vesicle but to a lesser extent as compared to that seen in the lateral prostate. No response of the ventral prostate to the ablation of the seminal vesicle was found in aged rats. Factors which might be involved in the cause of the prostate hypertrophy in absence of the seminal vesicle were discussed.

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The effect of parathyroid hormone (PTH) and/or calcitonin in vivo on the lysosomal enzyme activity of rat bone was studied. PTH caused a significant increase in the acidphosphatase and β-glucuronidase activity of the rat tibia in a dose-related manner. Calcitonin also caused a significant increase in the acid-phosphatase of the tibia. Administration of calcitonin did not counteract the PTH-induced increase in the enzyme activity. These results may give rise to some doubt on the hypothesis that lysosomal enzymes play a vital role in the process of bone resorption.

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The effects of melatonin administration and pinealectomy on the milk ejection response were studied in the rat. The amounts of milk obtained by a litter during 1 hr suckling and during an additional 30 min suckling after 1 I. U. of oxytocin injection, following 7 or 8 hr separation from the mother on the 10th or 16th day of lactation, were considered as the naturally ejected milk and the residual milk and used as the index of the milk ejection response. Melatonin in doses of 0.8 or 1.6 mg was injected subcutaneously into the mother 2 hr before the suckling commenced. The amounts of the naturally ejected milk and the residual milk were not significantly influenced by these treatments compared with saline injected controls. The pinealectomized and shamoperated female rats were bred and the postpartum lactation was studied. No significant difference was observed between the 2 groups in the litter growth for 12 days from the 4th day of lactation, the total feed consumption of the mother during this period and also the milk ejection response determined on day 16 of lactation. Thus, the administration of melatonin and pinealectomy did not exert any significant effect on the milk ejection response under these experimental conditions. Also, pinealectomy did not affect the incidence of the vaginal estrous smear and the length of gestation period.

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Oral administration of probenecid augmented urinary clearance of, trichloroacetic acid precipitable ¹³¹I-insulin in six men who were injected with tracer dose of ¹³¹I-insulin intravenously. The increments were 16 to 423 % above the control value (P<0.05). In other eight men, endogenous insulin in urine and plasma was measured by radioimmunoassay method. Apparently increased responses in urinary insulin excretion and urinary insulin clearance were observed after probenecid administration. The percentage increases of the insulin excretion and the insulin clearance beyond the control values were 2 to 200 (P<0.01) and 7 to 200 (P<0.01), respectively.
It was suggested that insulin was reabsorbed at the proximal convoluted tubules and that probenecid affected this reabsorption mechanism.

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