A simple technique for measuring urine calcitonin (CT) was established using a sensitive radioimmunoassay (RIA) system for plasma human calcitonin (hCT). To extract urinary CT, urine samples were fractioned by gel chromatography on a column (0.8×20cm) of Bio Gel P-2. Recovery of synthetic (1-32) hCT was 86.1±6.2% and the intra-and inter-assay coefficients of variation in RIA were 5.9 and 8.2%, respectively. Dilution curves of the urinary CT after gel-filtration were parallel with the standard curve. In 11 patients with medullary carcinoma of the thyroid (MCT), the CT levels of the urine (in ng/mg Cr) were 3.4 to 20.8 times higher than those of the plasma (in ng/ml), and a significant positive correlation (r=0.93, P<0.001) was obtained between the urinary and plasma levels of CT in these 11 patients. In 32 normal subjects, the CT levels of the urine (in pg/mg Cr) were only 0.41 to 5.1 times of those of the plasma (in pg/ml), and a weak positive correlation (r=0.408, P<0.05) was obtained between these two levels. However, urinary CT levels in normal subjects apparently reflected a rise in endogenous plasma hCT in response to calcium infusion (4mg/kg B.W. for 1min) and that of exogenous plasma CT when synthetic (1-32) hCT (500μg for 1min)
Following gel filtration on a Bio Gel P-30 1.5×80cm column, larger molecular forms of CT than (1-32) hCT were found in the urine not only patients with MCT but also of normal subjects after infusion of calcium or synthetic (1-32) hCT. was injected intravenously.
It is concluded that measurement of urine CT is useful not only for diagnosis of MCT but also for evaluating CT metabolism in normal subjects.

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The glycoprotein hormone α-subunit was extracted and purified from the urine of a patient with undifferentiated carcinoma producing isolated α-subunit. Its final specific immunoactivity was 0.92 (mg α-subunit/mg protein). The α-subunit exhibited virtually identical immunoantigenecity to hCG-α antiserum with standard hCG-α. The molecular weight of the α-subunit determined by gel chromatography on Sephadex G-100 was greater than that of standard hCG-α dissociated by urea in vitro. By SDS disc electrophresis, however, the α-subunit moved faster than hCG-α separated by mercaptoethanol reduction. The amino acid composition of the α-subunit was quite similar to that of standard hCG-α. In the isoelectric focusing, the major components of the α-subunit from undifferentiated carcinoma and the α-subunit from urine of normal pregnant women (third trimester) were distributed over the range from pH3.5 to 6.0, while standard hCG-α was distributed in the fractions ranging from pH6.0 to 8.0. The result of a combination study in vitro indicated that both α-subunits from undifferentiated carcinoma and from urine of normal pregnant women did not actively combine with hCG-β.
These results suggest that the α-subunit secreted by undifferentiated carcinoma is virtually identical with standard hCG-α as the protein moiety but differs in regard to carbohydrate moiety, and also suggest that the excess of α-subunit, which is not associated with β-subunit, may have undergone some intracellular modification, and consequently, the electric charge of the freely secreted α-subunit changes and it no longer has the ability to combine with the β-subunit.

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In an attempt to elucidate the dopaminergic involvement in the regulation of the effect of angiotensin II on the adrenals, plasma aldosterone response to angiotension II infusion (5ng/kg/min, for 60 minutes) was studied in five normal volunteers in various experimental conditions.
Prior infusion of dopamine (3μg/kg/min) or saline (1000ml/hour) caused an attenuation of the aldosterone response to angiotension II. Concurrent infusion of a dopaminergic antagonist, metoclopramide (10μg/kg/min), abolished the inhibitory effect of doamine and saline.
These results suggest that the dopaminergic mechanism is involved in the adaptive aldosterone response of the adrenal to acute saline loading in man.

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Plasma GH response to insulin-induced hypoglycemia was examined in four girls with idiopathic precocious puberty before and during treatment with cyproterone acetate (CA) for 13-41months. Although the baseline plasma GH level did not change during CA treatment, the peak concentration of plasma GH in response to insulin-induced hypoglycemia was significantly (P<0.05) lower in patients during CA treatment than before CA therapy. These findings indicate that prolonged administration of CA partially suppresses GH secretion

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The metabolism of progesterone bound to uterine nuclear progesterone receptors was accelerated in vitro by incubation at 25°C for 30min with NADPH generator. The characteristics of progesterone metabolites and receptors were examined by ³H-R5020 exchange assay. Progesterone bound nuclei were prepared from uteri of estradiol-primed progesteronetreated ovariectomized rats. The specific nuclear R5020 binding sites examined by exchange assay were identified as specific progesterone receptors by the binding specificity of R5020 to progesterone receptors, their high affinity for progesterone, and the increase in the number of specific binding sites in response to a progesterone injection.
Major metabolites of progesterone specifically bound to nuclear receptors by incubation with the cofactor were 5α-dihydroprogesterone (5α-DHP) and 3α-hydroxy-5α-pregnan-20-one. The relative binding affinity of the progesterone receptor for 5α-DHP at 0°C was 27.5% of progesterone, but 3α-hydroxy-5α-pregnan-20-one had no binding affinity for the receptor. Incubation of the nuclei in the presence of NADPH generator decreased the number of R5020 binding sites from 143 fmol to 25 fmol per 100μg DNA, and increased the dissociation constant of the receptor with progesterone from 2.56nM to 7.78nM.
Results suggest that after gene activation, the specific binding sites of progesterone to nuclear receptors may be denatured in the presence of NADPH, causing both progesterone and receptors to dissociate from the receptors and chromatins, respectively, and that the dissociated progesterone may be converted to 5α-reduced pregnanes which have lower affinity for the receptor.

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The mechanism of the hypoglycemic action of sulfonylureas during long-term treatment was investigated in twenty-four patients with noninsulin-dependent diabetes mellitus treated for 1.5 to 19yr in the out-patient clinic. The subjects received the first oral glucose tolerance test (OGTT) while on sulfonylureas and the second OGTT one month after their withdrawal. As the degree of elevation of the fasting plasma glucose level after withdrawal varied, the subjects were classified into two groups. Fourteen subjects showing an increase of more than 15mg/dl were arbitrarily designated as group I, and the rest as group II The mean fasting plasma glucose of group I was 134±4mg/dl (mean±SE) and 194±14mg/dl with and without sulfonylureas, respectively. Group II did not exhibit any significant change in fasting plasma glucose. A mean fasting serum IRI of either group was not changed. In group I, a mean glucose area of 807±31mgμh/dl on OGTT increased significantly to 1121±72mg·h/dl (p<0.001) and, at the same time, a mean IRI area decreased significantly from 102±10μU-h/ml to 73±7μU-h/ml (p<0.001). The ratio of IRI area to glucose area, which might indicate the responsiveness of pancreatic B cells to hyperglycemia, was reduced on an average by 48% in group I. However, group II showed no significant change in the mean value of the glucose area, IRI area or the ratio one month after the discontinuation of sulfonylurea treatment. These findings suggest that the insulinotropic action of sulfonylureas is maintained even after long-term treatment and contributes to their antidiabetic effect.

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The case of a 27 year-old woman with typical manifestations of multiple endocrine neoplasia type II b is reported. Medullary carcinoma of the thyroid was detected on the occasion of an operation for goiter when she was 22years of age. Constipation due to megacolon caused by intestinal neuroma had persisted since childhood. Neuroma of the tongue and lips, hypertrophic corneal nerve and Marfanoid habitus were also found. The presence of pheochromocytoma was suggested in view of the positive cold pressor and results of glucagon loading tests, but this remains inconclusive. There was prolonged and exaggerated response of growth hormone and luteinizing hormone after provocative tests for anterior pituitary gland, in spite of normal basal levels. Screening of her family members for medullary carcinoma of the thyroid was carried out by measurement of immunoreactive calcitonin. Two siblings were shown to be hypercalcitoninemic, presumably due to occult medullary carcinoma of the thyroid. This case appeared to be the first in Japan showing multiple endocrine neoplasia type II b accompanied by familial hypercalcitoninemia.

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The present study was performed in order to elucidate the mechanism of the recruitment of follicular growth and subsequent ovulation after ovarian wedge resection (WR). Seven patients with a diagnosis of PCO underwent WR. After taking 4 or 5 preoperative blood samples in the morning after their hospitalization, blood was obtained following the operation at 3-h intervals for the first 48h and at 1-3day intervals thereafter for 9-33days. These samples were analyzed for LH, FSH, estradiol, progesterone and androstenedione. Each ovarian tissue obtained by the operation was processed for histological examination. In 5 patients, the ovaries appeared to correspond with typical PCO. In the remaining
2 patients, the histological features of the ovaries were consistent with a type of screlocystico-atrophic ovary according to Kusuda (1979). Some characteristic postoperative hormonal changes were observed in the patients with typical PCO who ovulated postoperatively. FSH started to increase from 3 to 30h after WR, and remained at higher levels for 2-7days. LH increased in a sporadic form shortly after WR and then declined in spite of sustained higher levels of FSH. Preoperative levels of androstenedione in the patients with typical PCO ranged between 2.0-3.4ng/ml, which exceeded serum levels in normal women. These high levels of androstenedione fell gradually following WR. There was an apparent decline of estradiol after WR in 2 out of 5 patients who ovulated postoperatively. A minor increase in progesterone occurred shortly after the operation, followed by a prompt decrease. In contrast, postoperative hormonal changes were minimal in the patients who did not ovulate postoperatively.
The present study was performed in order to elucidate the mechanism of the recruitment of follicular growth and subsequent ovulation after ovarian wedge resection (WR). Seven patients with a diagnosis of PCO underwent WR. After taking 4 or 5 preoperative blood samples in the morning after their hospitalization, blood was obtained following the operation at 3-h intervals for the first 48h and at 1-3day intervals thereafter for 9-33days. These samples were analyzed for LH, FSH, estradiol, progesterone and androstenedione. Each ovarian tissue obtained by the operation was processed for histological examination. In 5 patients, the ovaries appeared to correspond with typical PCO. In the remaining 2 patients, the histological features of the ovaries were consistent with a type of screlocystico-atrophic ovary according to Kusuda (1979). Some characteristic postoperativehormonal changes were observed in the patients with typical PCO who ovulated postoperatively. FSH started to increase from 3 to 30h after WR, and remained at higher levels for 2-7days. LH increased in a sporadic form shortly after WR and then declined in spite of sustained higher levels of FSH. Preoperative levels of androstenedione in the patients with typical PCO ranged between 2.0-3.4ng/ml, which exceeded serum levels in normal women. These high levels of androstenedione fell gradually following WR. There was an apparent decline of estradiol after WR in 2 out of 5 patients who ovulated postoperatively. A minor increase in progesterone occurred shortly after the operation, followed by a prompt decrease. In contrast, postoperative hormonal changes were minimal in the patients who did not ovulate postoperatively.
The postoperative hormonal changes including a decline in androstenedione, a temporary-minor increase in progesterone, a short-term sporadic increase in LH and a sustained increase in FSH may be involved in the mechanisms which account for the recruitment of follicular growth and subsequent ovulation after WR.

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A 25 yr-old woman patient was admitted because of convulsion. The diagnosis of pseudohypoparathyroidism was made on the bais of typical stigmata, lowered serum calcium, increased serum phosphorus and parathyroid hormone levels, and defective response in urinary excretion of cyclic AMP and phosphorus to exogenous parathyroid extract. Endocrine studies performed in the hypocalcemic state revealed several abnormalities of the pituitary gland such as an exaggerated response of TSH to TRH, high basal levels and exaggerated responses of LH/FSH and a blunted GH response to arginine-HCl, while there was no clinical evidence of hypothyroidism and hypogonadism. These abnormalities of anterior pituitary function were normalized after the restoration of normocalcemia by using 1α-hydroxy-cholecalciferol.
These results suggest that some endocrine abnormalities observed in pseudohypoparathyroidism might be functional and reversible disorders secondary to hypocalcemia rather than genetic ones.

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The correlation of Plasma β-N-acetylglucosaminidase (NAG) activity and the development of diabetic retinopathy was observed in 117 diabetic patients (male 52, female 65) who had been observed for 2years. The plasma NAG activity was measured at least 3 times per year (6-9 times altogether). The eye-ground findings at the beginning of the study and 2years later were studied according to Scott's classification. Forty-four percent (19 cases) of the 43 patients with higher NAG activity (<525nmole/h/ml) and 27%(20 cases) of the 74 patients with lower NAG activity (≤525nmole/h/ml) showed a worsening of the eye findings (p<0.05). The frequencies of patients showing a worsening of the eye findings in patients with higher fasting blood glucose (FBG) values (≥140mg/dl) and in patients with lower FBG values (<140mg/dl) were 45%(17 in 38 cases) and 28%(22 in 79 cases), respectively (p<0.1). When the NAG activity and the FBG value were considered together, there were 16 patients with both higher FBG values and higher NAG activity, 49 patients with either higher FBG values or higher NAG activity, and 52 patients with both lower FBG values and lower NAG activity. The frequencies of the patients who had a worsening of the eye findings were 56%(9 cases), 37%(18 cases), and 23%(12 cases), respectively. The difference was significant (p<0.05). In the present study, the plasma NAG activity showed no relation to diabetic retinopathy, but the results suggest that the plasma enzyme estimation may add further information to the FBG value and so help in predicting the development of diabetic retinopathy.

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Rabbit antiserum to bullfrog prolactin (A/S) or normal rabbit serum (NRS) was administrated to premetamorphic bullfrog larvae. Collagen synthesis in the tail fin was not affected by A/S. However, the enhancement of collagen synthesis induced by pimozide treatment was completely blocked by A/S. Premetamorphic tadpoles kept in 3×10^-8M thyroxine received A/S or NRS. A/S accelerated tail resorption. The results indicate that the endogenous prolactin is acting as an antimetamorphic hormone, although it is not certain that normally circulating level of prolactin contributes to promoting the growth of the tail fin in larval bullfrogs.

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For 4 to 8years we followed up 3 diabetic patients in whom the onset of diabetes seemed to be closely related to the well-documented Epstein-Barr virus infection (Case 1) or Coxsackie B4 virus infection (Case 2, 3). Although all developed acute ketosis-prone diabetes in the convalescent stage of the viral infections, the subsequent clinical courses were quite different from each other. Case 1 has remained consistently insulin-dependent and associated with positive islet cell antibody, gastric parietal cell antibody, thyroglobulin hemoagglutinating antibody and thyroidal microsomal hemoagglutinating antibody. Case 2 restored normal glucose tolerance. Case 3 has become noninsulin-dependent diabetes mellitus after a 6year interval. Thus, it is reasonably presumed that viruses could be responsible for the occurrence of different phenotypes of diabetes.

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The effect of castration on total 5α-reductase activity in transforming testosterone to 5α-reduced metabolites was studied in the sebaceous gland of male hamsters. The mean enzyme activity increased to more than twice the control level as early as 4days after castration and this increase remained almost unchanged at 14, 21 and 63days after castration. The administration of testosterone propionate or 5α-dihydrotestosterone to castrates led to a complete inhibition of the increase in enzyme activity and this inhibitory effect was blocked by cyproterone acetate. These data indicate that androgens may be regulators of 5α-reductase activity in the sebaceous gland of hamsters.

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Ten patients with anorexia nervosa were treated with intravenous hyperalimentation (IVH) and/or psychotherapy. The five patients were treated with both IVH and psychotheraoy. The five patients were treated with both IVH and psychotherapy. Their body weight rose from 66±3%(mean ±SE) to 78±6% of their ideal weight during hospitalization, and then to 91±5% during ambulatory observation for a period of 6 to 36months. Another group of 5 patients were treated only with psychotherapy. Their body weight increased 69±3% to 73±1% of their ideal weight during hospitalization, and then to 78±1% during during the observation period at the out-patient department during a period of 6 to 48 months. The former group gained more weight than the latter group during hospitalization (P<0.025) and during ambulatory observation (P<.025), respectively. These results suggest that IVH is one effective remedy for anorexia nervosa and that good results can be expected from IVH and psychotherapy used in combination.

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Bromocryptine, a dopamine agonist, effectively inhibited the black-adaptation of prometamorphic tadpoles of the bullfrog Rana catesbeiana. The melanophore index (MI) of bromocryptine-injected tadpoles was significantly lower than that of controls. Bromocryptine was also effective in lightening the skin color of the hypophysectomized tadpoles bearing a pituitary graft. When pimozide, a dopamine receptor blocker, was given to the tadpoles adapted to a white background, the MI increased significantly and their skin color became dark. However, pimozide was not effective in darkening the skin color of the hypophysectomized tadpoles. The injection of α-methyl-p-tyrosine (α-MPT), an inhibitor of tyrosine hydroxylase, markedly attenuated the background response of the tadpoles. After being transferred from a black to a white background, the skin color of α-MPT-treated tadpoles was still significantly darker than that of non-injected controls. On histofluorescence examination, numerous green catecholamine fluorescent nerve terminals were found among the glandular cells of α-MPT-injected and control tadpoles adapted to a black background. This green fluorescence in the pars intermedia (PI) of α-MPT-treated tadpoles disappeared 6h after exposure to a white background. However, catecholamine fluorescence in the PI of the controls did not decrease in a white background.
The present results suggest the possible involvement of dopamine in the background response of the bullfrog tadpoles. Since the background response of the tadpole skin color is dependent on the pituitary MSH, dopamine presumably inhibits MSH secretion by acting on the glandular cells of the PI when the animals are exposed to a white background.

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Cervical stimulation was used to induce synchronous ovulation in rats that were induced into constant estrus by exposure to continuous lighting. Anti-LHRH or anti-LH serum completely blocked the induced ovulation when administered iv within 5 or 40min after cervical stimulation. Peripheral concentrations of LH and LHRH hypothalamic content of LHRH were quantified before and at various intervals (0.5-70min) after cervical stimulation. The radioimmunoassay for LHRH employed a specific antiserum, OAL-513, with high affinity and specificity and highly purified ¹²⁵I-LHRH. Measurement of LHRH in extracts of 3-5ml of plasma gave values that were readable in the middle portion of the standard curve.
A two-fold increase in the LHRH concentration in peripheral plasma was observed 30sec after the start of cervical stimulation. The elevated LHRH level was sustained for 15min, though associated with large fluctuations. Serum LH levels started to rise 4 to 10 min and returned to the basal level 70min after cervical stimulation. The hypothalamic LHRH content continued to increase throughout the entire experimental period and attained 140% of the initial level. No significant deflection due to LHRH release was observed in the hypothalamic LHRH content. Changes in the peripheral hormone level after cervical stimulation were competent for chronologically reasoning the effectiveness of the antihormone treatment for blockage of the induced ovulation.
From these results it is concluded that LHRH release before the preovulatory LH surge in light-estrous rats was brief in duration and erratic in mode.

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Concentrations of arginine-vasopressin (AVP) in the cerebrospinal fluid (CSF) of 5 alcoholic patients and 6 healthy volunteers were determined by a radioimmunoassay.
The concentrations of AVP in the CSF of alcoholic patients were 2.93-6.17pg/ml (the mean value, 4.80±1.34pg/ml) and those of healthy volunteers 3.80-12.59pg/ml (the mean value, 9.87±3.19pg/ml). The AVP level in the CSF of alcoholics was significantly lower than that of normals (P<0.02).

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