Based on the results of a nationwide questionaire survey during the decade from 1963 in Japan, 68 cases of idiopathic aldosteronism were collected in order to investigate the actual treatment for this disorder performed in Japan. Idiopathic aldosteronism was usually treated by unilateral or subtotal adrenalectomy. Unlike resection of adenoma, adrenals surgery were not so effective and only 50%of cases obtained a favourable result. Surgical treatment was effective in 60.5% of cases of nodular hyperplasia while effective only in 26.3% of cases of diffuse hyperplasia. Opinions from answers to the questionaires favoured total bilateral adrenalectomy or subtotal adrenalectomy either with or without spironolactone administration.

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It is generally accepted that ectopic ACTH-producing tumors produce not only ACTH but β-MSH or β-LPH as well. Using a sensitive radioimmunoassay for βhendorphin, we have demonstrated the presence of β-endorphin immunoreactivity with size heterogeneity according to Sephadex gel chromatography and sodium dodecyl sulfate polyacrylamide gel electrophoresis in 6ectopic ACTH/β-LPH-producing tumors, providing further evidence for the role of a common precursor to ACTH and β-LPH/β-endorphin in the peptide biosynthesis in these tumors, in a manner similar to the biosynthetic events in the pituitary gland of several species.

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The time course of adaptation of the serum calcium level to the gradual deprivation of parathyroid hormone was studied in adult male and female rats. In addition, the role of thyrocalcitonin and thyroid hormones in adaptive changes in serum calcium was assessed in the surgically parathyroidectomized animals. Simultaneous bilateral parathyroidectomy, thyroparathyroidectomy or the second unilateral parathyroidectomy performed 72hr after the first unilateral parathyroidectomy produced a prompt fall in serum calcium level leading to the lowest value at 10hr and the significantly lower calcium level retained for one week-observation. Unilateral parathyroidectomy resulted in a transient fall in the serum calcium level and to a rapid return to the subnormal range in 24hr in both sexes. When the second unilateral parathyroidectomy was carried out 1 or 6 weeks after the first unilateral parathyroidectomy, the serum calcium in female rats showed a slight decrease until 10hr and returned to the normal level in one week, but in male rats no further decline or a gradual decrease was seen. Bilateral thyroidectomy performed 10weeks after the second unilateral parathyroidectomy resulted in a gradual increase in the serum calcium above the normal range in female rats. In male rats, the serum calcium level tended to drop until 10hr and returned to the initial level or to the normal range. Bilateral thyroidectomy performed one week after simultaneous bilateral parathyroidectomy led to a further decline in serum calcium in both male and female rats. The results indicate that adaptation of the serum calcium level toward the normal range occurs in the absence of parathyroid hormone in adult male and female rats if the parathyroid hormone is gradually deprived. A greater ability of female rats to restore the calcium level, especially seen when thyroidectomized after adaptation to the lack of parathyroid hormone, suggests that estrogens play a significant role in the homeostatic control of serum calcium in chronic disorders in calcium regulation.

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In diabetic patients plasma levels of pancreatic polypeptide (PP) increased four fold after intramuscular injection of secretin (50CHRU, Eisai Co.) in spite of the lack of response of plasma insulin, plasma glucagon and blood glucose levels. In control subjects, PP levels did not change significantly after secretin injection. Since pancreatic polypeptide has is known to have an inhibitory effect on the exocrine pancreas, the present study suggests the possibility that disturbed function of the exocrine pancreas in diabetic patients could be related to the remarkable response of PP to secretin-stimulation.

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Pancreatic islet-cell antibodies (I.C.Ab.) were detected in the sera of6of123 patients with insulin-dependent diabetes mellitus of recent onset, compared with only 2positive results among the 434 control sera. The prevalence of humoral I.C.Ab. was strongly dependent on the duration of the diabetes, being 4 of 6 I.C.Ab. positive patients during the first year from diagnosis and falling to 2 of 6 I.C.Ab. positive patients at one to three years. Over four years from the time of diagnosis, there was no I.C.Ab. in the sera of the diabetics. Six I.C.Ab. positive in our group of 123 diabetic patients showed no association with any particular B locus antigen or DYT.

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In 3 patients with medullary thyroid carcinoma, plasma calcitonin levels showed 3 distinct peaks associated with a simultaneous rise in plasma gastrin after each meal. It is suggested that endogenous gastrin secreted following food intake stimulated the calcitonin secretion from the tumor. The peak of the plasma calcitonin secretion after the evening meal was less prominent than that for breakfast or lunch, while no significant differences were observed in peak values in plasma gastrin after each meal. The reason for this discrepancy remains to be clarified.

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Two ancreaticp chambers constructed of plastic tube and ultrafiltration membrane and containing the minced pancreases of five neonatal rats were implanted in the omentum of totally pancreatectomized diabetic dogs. Blood glucose levels in the diabetic dogs leveled off just after operation, in contrast with those in control animals, in which vacant chambers were implanted, and began to decrease about a week after the transplantation. Blood glucose levels fell to less than 150mg/100ml within three weeks. The neonatal rat pancreases in the pancreatic chamber produced a near normal plasma glucose and insulin response to an intravenous glucose tolerance test on the 20th day after transplantation. Removal of the pancreatic chamber from the experimental dogs after normalization of blood glucose levels, caused a rapid elevation of blood glucose levels, and lead to death within four days. No rejection reactions were observed in the course of the experiment. These findings suggest that pancreatic transplantation with the pancreatic chamber is potentially useful for the treatment of diabetes.

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In pregnant rats ovariectomized on Day 14 of pregnancy (sperm present=Day1), the daily injection of 4mg progesterone maintained normal pregnancy up to Day 17, but injured fetuses bearing hematomata on their extremities appeared very frequently there after, in spite of successive injections of progesterone. The addition of 0.2μg estradiol-17β to the daily dose of progesterone for two suc-cessive days between Days 15 and 18 of pregnancy prevented the occurrence of fetal injuries. Estradiol-17β was found to be more effective in preventing fetal damage than estrone or estriol. The results suggest that while progesterone is essential for the maintenance of pregnancy, estrogen is also necessary at the time when the conceptus elongates and becomes cylindrical.

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The effects of high-fiber diet on the metabolic states in streptozotocin-induced diabetic rats were investigated. The animals were divided into three groups: group A fed on a diet containing5% of fiber (bagasse), group B paired-fed on a control diet and group C fed on a control diet ad libitum. The body weight gain was greater and the fasting blood sugar level was lower in A than B and C. The plasma triglyceride level was lowest in A, while no significant difference in the serum total cholesterol level was observed between A and B. Plasma glucagon levels were decreased in A and increased significantly in B and C. Plasma insulin levels were not changed in these groups.
These results support the theory that a high-fiber diet is an effective therapeutic regimen for the control of metabolic derangement in diabetics.

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Urinary metabolites of [6, 7-³H]-estrio1-3-glucosiduronate and of [6, 7-³H]-estriol in intact female rabbits were analyzed. The separation of urinary metabolites was performed by countercurrent distribution followed by DEAE-Sephadex A-25 column chromatography. Each conjugate was then hydrolyzed with the enzymes and the aglycone thus liberated was identified. In either case, major urinary metabolites were found to be diconjugates, a considerable part of which was glucosiduronate-Nacetylglucosaminide of 17-epiestriol. In addition, estriol-16-glucosiduronate or monoglucosiduronate of 17-epiestriol was identified as a minor urinary metabolite of [6, 7-³H]-estriol. From these results, it was concluded that the greater part of the estriol-3-glucosiduronate was converted to diconjugates and that estriol-3-glucosiduronate was probably an intermediate metabolite in the conversion pathway from estriol to diconjugates in this species.

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In order to elucidate the presence of free FSH-β and LH-β and their relation to the native hormones, immunoreactive FSH (IR-FSH), IR-LH, IR-FSH-β, and IR-LH-βsubunits in the rat anterior pituitary and serum from 1200hr of proestrous day to 0600hr of estrous day were measured by radioimmunoassay. The amounts of IRFSH-β found were always more than those explained by the cross-reaction between FSH, and IR-FSH and IR-FSH-β. On the other hand, IR-LH-β was always less than the amount explained by the cross-reaction with LH, and changes in IRLH and IR-LH-β were parallel.
There was also a difference between IR-FSH and IR-FSH-β gel-filtration patterns in the rat anterior pituitary extracts. IR-FSH was eluted as a single peak, while IR-FSH-β was found in three different regions. The first peak appeared near the void volume, the second corresponded to that of FSH, and the third was in the region of smaller molecules which was thought to be free FSH-β. The first and the third peaks ofI R-FSH-β changed characteristically during the estrous cycle.
Radioiodinated FSH-β, when incubated with the anterior pituitary extracts and applied to gel-filtration on Sephadex G-100, appeared also in three major peaks corresponding to those of IR-FSH-β in the extracts. The first peak seemed to be aggregated or non-specifically bound FSH-β and the second seemed to be FSH, while the third was thought to be free FSH-β.
These results indicated the presence of free FSH-β in the rat anterior pituitary and serum, and raise a doubt about free LH-β.

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Seventeen women with anorexia nervosa were studied before and during weight gain. The mean body weight was 93.8% before onset of illness, 82.9% at the beginning of amenorrhea and 61.8% at the minimum weight, each expressed as a percentage of the standard weight (SW). Basal serum LH and FSH level were significantly low in the lower weight patients, and increased with weight gain, with a linear correlation to the percent of SW. The LH response to 100μg of LH-RH was impaired in the lower weight group, and was improved with weight gain. The LH response in those whose weight had increased to 70% or more of the SW was often excessive and the maximum levels were significantly higher than in normal women. The FSH response to LH-RH was well maintained even in the lower weight group, but the maximum response was delayed. There was a significant correlation between improvement in the LH response and weight gain, but no significant correlation was found between FSH response and body weight. Menstrual cycles were restored in some who showed 100mIU/ml or more of the maximum LH response, but no definite relationship was found between the LH or FSH response and the resumption of menstruation. Though the weights at the cessation and at the resumption of menstruation differed from case to case, the two weight levels were almost the same in each individual. These results indicate that the critical body weights for maintaining menstrual cycle are inconsistent and that the resumption of menstruation may not be accounted for only by the recovery of such a tonic regulation as seen in the responsiveness to LH-RH following weight gain but by the restoration of the individual critical weight.

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Thyroxine (T₄) is known to be converted to triiodothyronine (T₃) in rat liver microsomes. An endogenous stimulatory factor for the conversion of T₄ to T₃ was identified as reduced glutathione (GSH) by Sephadex G-15 gel chromatography of rat liver extract. The production of T₃ in rat liver microsomes was maximally stimulated above a GSH concentration of 4mm, and an approximately 5-fold stimulation was attained. This degree of stimulation was approximately 10 times less than that observed with dithiothreitol (DTT).
Activity in the conversion of T₄ to T₃ was solubilized from the microsomes using 0.1% deoxycholate. When the solubilized microsomal preparation, pre-treated with DTT or GSH, was subjected to gel filtration on a Sepharose CL-6B column to separate the preparation from the thiol, almost no T₃ producing activity was observed in any of the collected fractions. However, when DTT or GSH was added to the fractions containing high molecular weight components, the activity of the production of T₃ was sustained. This finding indicates that these thiols play an essential role in the conversion of T₄ to T₃, possibly acting as cofactors.

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Inhibitory effects of unlabeled iodothyronines on the metabolism of thyroxine (T₄), 3, 3', 5-triiodothyronine (T₃) and 3, 3', 5'-triiodothyronine (reverse T₃, rT₃) were investigated in continuously cultured monkey hepatocarcinoma cells which showed a rapid metabolism of the thyroid hormones.
Nonphenolic ring deiodination of [3', 5'-¹²⁵I]-T₄ and [3'-¹²⁵I] T3 was strongly inhibited by excess T₃, 3, 5-diiodothyronine (3, 5-T₂) and T₄, whereas rT₃ was the least effective inhibitor.
Phenolic ring deiodination of [3', 5'-₁₂₅I]-rT₃ was strongly affected by excess unlabeled rT₃. However, the inhibitory effect of T₄, T₃ and 3, 5-T₃ was much weaker than that of rT₃.
It was concluded that rT₃ is apparently the most effective inhibitor of phenolic ring deiodination but the least effective inhibitor of nonphenolic ring deiodination.

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Serum concentrations of 25-hydroxyvitamin D (25-OH-D) and 24, 25-dihydroxyvitamin D [24, 25-(OH) ₂-D] were measured in lipid extracts of 1ml of human sera by a competitive protein binding assay. 25-OH-D and 24, 25-(OH) ₂-D were isolated from the lipid extracts by Sephadex LH-20 column chromatography. The 24, 25-(OH) ₂-D fraction on the Sephadex LH-20 columns were further purified by high pressure liquid chromatography prior to assay. Serum levels of 25-OH-D and 24, 25-(OH) ₂-D in normal males were similar to those in normal females throughout each age group. Serum levels of 25-OH-D and 24, 25-(OH) ₂-D in newborns were 8.28±1.68ng/ml (mean±SD) and 0.55±0.16ng/ml, respectively, which were significantly (p<0.001) lower than those in adults (21.3±4.8ng/ml of 25-OH-D and 1.55±0.31ng/ml of 24, 25-(OH) ₂-D). A seasonal variation was demonstrated in serum levels of 24, 25-(OH) ₂-D as well as those of 25-OH-D. Serum levels of 24, 25-(OH) ₂-D were highly correlated (γ=0.884, p<0.001) with those of 25-OH-D in normal human subjects, and the percentage ratio of 24, 25-(OH) ₂-D/25-OH-D was 7.4±1.4%(mean±SD), irrespective of age or seasonal variations.

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An angiotensin II antagonist, [sacrosine, isoleucine] angiotensin II, was infused into thyrotoxic patients. Blood pressure was monitored before and during the infusions to investigate whether the renin-angiotensin-aldosterone system was involved in the maintenance of blood pressure in normotensive and hypertensive thyrotoxic patients.
Five out of 17 normotensive patients with hyperthyroidism showed more than a 10 mmHg decrease in mean blood pressure in response to the infusion (responders), while the remaining 12 patients showed no substantial change in blood pressure (non-responders). The infusion caused little change in blood pressure in 8 hyperthyroid patients with systolic hypertension. The mean levels of serum thyroxine, triiodothyronine, plasma renin activity and plasma aldosterone concentralion in the normotensive responders were significantly higher than the values in the normotensive non-responders. There were no significant differences in these laboratory values between the hypertensive patients and the normotensive non-responders except that serum triiodothyronine levels were significantly higher in the hypertensive patients.
The present study indicates that increased activity of the renin-angiotensinaldosterone system is involved in the maintenance of blood pressure in most normotensive patients with severe hyperthyroidism, while hypertension in patients with hyperthyroidism is not angiotensin II dependent.

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Cytosol of human benign prostatic hypertrophy bound to R 1881 in a high affinity manner. Most of the protein which bound to R 1881 was recovered in the precipitate of a 0-30% saturation of ammonium sulfate, and was eluted in the void volume on a Sephadex G-200 column. The binding of cytosol to R 1881 was more inhibited by progestins than by dihydrotestosterone and estradiol-17β. The binder therefore seemed to be different from dihydrotestosterone-binding protein. The R 1881-binding component extracted from the nuclei by 0.4M KCl bound also to dihydrotestosterone in a high affinity manner. Cytosol prelabeled with R 1881 was bound to the nuclei in a nonsaturable process, and the extraction pattern of R 1881 by 0.4M KCl from the nuclei was almost identical to that in the case of dihydrotestosterone as the ligand. These results suggested that a part of the cytosolic protein which bound to R 1881 entered the nuclei where it bound to nuclear such components as dihydro-testosterone-binding protein.

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The effect of electrochemical stimulation of the medial preoptic area (MPO) and the hypothalamic arcuate nucleus (ARC) on LH release was compared among longterm ovariectomized (OVX), ovariectomized rats treated with estradiol benzoate (OVX-E) and proestrous (PE) rats under pentobarbital anesthesia. The MPO stimulation failed to facilitate LH release in OVX rats whereas the stimulation increased serum LH levels in both OVX-E and PE rats. The ARC stimulation resulted in an elevation of serum LH in OVX and PE rats. The time course of serum LH elevation after the electrochemical stimulation of the MPO or the ARC was different between OVX-E and PE rats. In PE rats serum LH concentrations began to rise 20-30min after the stimulation of the MPO or the ARC with peak values obtained around70-90min. Serum LH started to elevate immediately with peak values in 10-20min following the ARC stimulation in OVX rats and the MPO stimulation in OVX-E rats. The time courses for changes in serum LH concentrations following LH-RH administration were similar in OVX and PE rats. From these results, the lack of circadian rhythm in serum LH levels in long-term OVX rats may be due to the inability of the MPO to re-spond to the stimulus generated from circadian pacemaker (s). The cause of the delay observed between the stimulation of the MPO and LH rise in PE rats may not exist in the levels of neural transmission between the MPO and the ARC or the pituitary, but in the level of the mediobasal hypothalamus.

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The lipolytic activities with acid pH optimum were extracted from the acetone powders of the pregnant and lactating mouse mammary glands. Since the activities were strongly inhibited by human serum and albumin which were required for lipoprotein lipase assay, they were considered to be ascribable to lipase (s) other than lipoprotein lipase. Despite the fact that the amount of fatty acid released by the extract prepared from the glands in pregnancy (P-extract) was proportional to the incubation time, the release of the fatty acid by the extract from those in lactation (L-extract) ceased during incubation for a short time. The cessation, however, was avoided by preincubating the L-extract at 50°C for 10 min before assay. In the presence of L-extract, the lipolytic activity in the P-extract was also almost completely lost after a short incubation. From these results, the existence of a heat labile inactivator of the lipolytic activities in lactating mouse mammary glands was suggested.

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Binding of ¹²⁵I-human chorionic gonadotropin (HCG) to homogenates of the human corpora lutea of the menstrual cycle and pregnancy was examined in vitro. While corpora lutea of the menstrual cycle bound ¹²⁵I-HCG specifically, the corpora lutea of pregnancy from 8 weeks' gestation bound little or none of the added ¹²⁵I-HCG. In the corpus luteum of the menstrual cycle the dissociation constant for HCG and the number of binding sites were analyzed by a Scatchard plot. However, from these observations along with the findings of earlier reports, it may be suggested that LH-HCG receptors remain reduced in number in the corpus luteum of pregnancy.

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A woman with oat cell carcinoma of the lung showed the typical findings of the syndrome of inappropriate secretion of ADH initially during her hospital course. Ectopic production of ADH was indicated. The presence of ectopic production of ACTH was then suggested after the appearance of the elevation of plasma cortisol and ACTH which was not suppressed by dexamethasone administration. The laboratory findings of metabolic alkalosis and hypokalemia were also consistent with hyperadrenocorticism. In tumor tissue obtained by biopsy, ACTH and ADH were proven to be present by radioimmunoassay as well as nicotine-stimulated-neurophysin and estrogen-stimulated-neurophysin. This was a rare case in which the simultaneous production of ADH and ACTH was clinically diagnosed. It is suggested that the elevation of neurophysins in plasma is of value in the diagnosis of ectopic production of ADH.

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