Serum testosterone concentrations have been determined during the menstrual cycle and early pregnancy in the bonnet monkey, Macace rediata. During the cycle, there is an increase around the time of ovulation and a secondary peak in the late luteal phase. In pregnancy, there is a distinct peak around 23-25 days, a period which corresponds to the peak of chorionic gonadotrophin reported by Atkinson et al.(1975) in Rhesus monkeys. Administration of exogenous hCG causes a significant rise in the serum testosterone level in cycling monkeys.

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The effect of a potent opioid peptide FK 33-824, [D-Ala², MePhe⁴, Met (O) ⁵-ol] enkephalin, on prolactin (PRL) release from rat anterior pituitary was investigated in vivo and in vitro. Systemic administration of FK 33-824 (1, 10 and 100μg/100g BW i. p.) caused a rapid and dose-related increase in plasma PRL in urethane-anesthetized male rats. Naloxone (125μg/100g BW i.v.) abolished PRL responses to FK 33-824. In the rat pretreated with either reserpine (2 mg/100 g BW i. p.), α-methyl-p-tyrosine (30 mg/100g BW i. p.) or pimozide (50μg/100 g BW i. v.), basal plasma PRL levels were elevated and FK 33-824 injection did not further increase plasma PRL. In contrast, neither 5, 6-dihydroxy-tryptamine (50μg/rat, i. c. v.) nor diphenhydramine (100μg/100g BW i. v.) treatment influenced the plasma PRL response to FK 33-824. FK 33-824 (10^-8-5×10^-5 M) did not stimulate PRL release from dispersed anterior pituitary cells in vitro nor attenuate the inhibitory effect of dopamine (5×10^-7 M). These results suggest that central dopaminergic mechanisms are involved in PRL release induced by the opioid peptide.

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The role of vitamin E in the endocrine system, in particular the pituitary-gonadal axis, was studied in humans and male rats by examining the hormonal differences between vitamin E deficient and supplemented conditions.
In vitamin E deficient rats, pituitary content and basal plasma level of FSH and LH were significantly lower than those of the control rats, but testicular content and basal plasma level of testosterone were not significantly changed.
On the other hand, in vitamin E supplemented rats, FSH and LH content in pituitary tissue was significantly higher than that of the controls, but there was no significant rise in basal FSH and LH level in plasma. The testosterone level was significantly elevated in both testicular tissue and plasma. It was also demonstrated that basal plasma testosterone and F. T. I. were increased in normal male subjects following oral vitamin E administration and the responsiveness of plasma testosterone levels to HCG was significantly higher during vitamin E administration than before administration.
These results suggest that vitamin E may play an important and potent role in hormone production in the pituitary-gonadal axis in humans and rats.

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A case of tertiary hyperparathyroidism with a parathyroid adenoma and hyperplasia was described as the first report in Japan.
A 24-year-old man manifesting hypercalcemia had been treated with hemodialysis for 9 years. On admission, clubbed fingers, richitic rossaries and a palpable node in the neck were the major physical findings. Laboratory examinations revealed hypercalcemia and elevated levels of plasma parathyroid hormone (PTH) in a c-terminal assay. Nevertheless the levels of PTH found by a n-terminal assay disclosed an only small increase. The PTH levels were scarcely decreased after a bolous injection of calcium gluconate. A large tumor corresponding to the palpable node was resected. Histologically, the tumor was an adenoma with thick fibrous capsule and interparenchymal bands. Other parathyroid glands showed secondary clear cell hyperplasia without signs of cellular hyperactivity.

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Kinetic studies on ¹²⁵I-insulin binding and degradation were examined using liver plasma membrane and cytosol fractions from fed and fasted rats.
Liver plasma membranes of 72h fasted rats bound twice as much insulin as did membranes of fed rats. Scatchard analysis showed that the enhancement of ¹²⁵I-insulin binding in fasted rats was due to an increase of insulin receptor concentrations in the membranes. Specific activity of insulin degradation by plasma membranes was about 10% of the activity by the cytosol fraction and showed no significant difference between fed and fasted rats. On the other hand, insulin-degrading activity in the cytosol fraction from fasted rats was significantly lower than fed rats (P<0.02). Quantitative analysis of insulin degradation in the cytosol fraction revealed a similar Km for both groups (1.8 to 2.5×10^-7M), while the maximal velocity (V_max) in fasted rats was significantly lower than that of fed rats (P<0.02).
The antiserum to insulin-degrading enzyme (IDE) purified from pig skeletal muscle was able to remove insulin-degrading activity in both the cytosol (34±7 vs 79±3% of the control, P<0.001) and plasma membrane fractions (49±7 vs 81±6% of control, P<0.01) by immunoprecipitation when compared with normal rabbit serum. Furthermore, ¹²⁵Iinsulin binding to plasma membranes significantly increased in the presence of the antiserum (121±9% of control, P<0.05).
These data suggest that the number of insulin receptors in the plasma membrane increases, whereas the content of insulin-degrading enzyme (s) in the cytosol fraction decreases in the hypoinsulinemic state. Since insulin-degrading activity in plasma membranes does not change in the fasted state, insulin seems to be mainly degraded by intracellular enzyme (s) including IDE rather than the insulin-degrading system of plasma membranes in the rat liver.

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The present study was undertaken to determine the capacities of granulosa cells and thecal tissues from polycystic ovaries, in comparison to those from normal ovaries, to secrete androgens in vitro. Isolated granulosa cells and thecal tissues from normal and polycystic ovaries were cultured with or without luteinizing hormone (LH), human chorionic gonadotropin (HCG), or follicle stimulating hormone (FSH) for 12 days.
The cultured granulosa cells from both groups produced insignificant levels of androgens and, moreover, the addition of exogenous LH had no stimulatory effect on testosterone accumulation. The cultured thecal tissues secreted large amounts of androstenedione and relatively large amounts of progesterone, estradiol and testosterone. On a per unit mass basis, in the absence of exogenous gonadotropin, the cultured thecal tissues from polycystic ovaries produced significantly more androgen than those from normal ovaries. Comparative studies of normal and polycystic ovaries revealed that the cultured thecal tissues from normal ovaries were more reactive to exogenous LH stimulation than those from polycystic ovaries, but that the net increase in androgen production due to LH stimulation did not differ significantly between the cultured thecal tissues from normal and polycystic ovaries.
The present observations suggest that thecal tissues, but not granulosa cells, may be partly responsible for hyperandrogenism in patients with polycystic ovaries. It is possible that the excessive androgen production in the cultured thecal tissues from polycystic ovaries may be due to the in vivo exposure to chronic LH stimulation.

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The present study demonstrates the effect of glucosamine on the functional maturation of cultured B cells of the neonatal rat. When B cells had been maintained at a physiological concentration (5.5mM) of glucose for 7 days, a drop in the stimulatory effect of 16.7mM glucose on insulin release and biosynthesis was observed together with a reduced insulin content. By contrast, the sensitivity of glucose-induced insulin release was increased after one week of culture with 5.5 mM glucose and 5mM glucosamine. And both the insulin content and glucose-induced insulin biosynthesis also remained at the same level as observed at the first day of culture with 5.5 mM glucose alone.
In summary, it was suggested that glucosamine-supplemented culture may result in the transition of B cells of neonatal rat from a poor glucose sensitivity to adult-type response of insulin release.

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Cytosol of the benign hypertrophic human prostate was prepared in a low salt medium and then the concentration of salt was increased to 0.4 M with KCl (0.4 M KCl-cytosol). This preparation showed a high affinity binding to R 1881 and the binding was specific for androgens. These results suggest that the binding of the preparation to R 1881 was due mainly to the cytosolic androgen receptor. The R 1881 binding component in the 0.4 M KCl-cytosol was sedimented at 3S by sucrose density gradient centrifugation. The small sedimentation coefficient of the binder seems to be due to the high concentration of salt and not to degradation by proteolytic enzymes in the preparation. The molecular weight, Stokes radius and frictional ratio of this binding component were 32, 000, 25.9 Å and 1.24, respectively.

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The effect of the decidualization induced by the administration of sex steroid hormones on the human endometrial PRL contents and the mechanism of synthesis and secretion of PRL in this decidualized endometrium of non-pregnant women were investigated. The PRL contents increased in proportion to the degree of decidualization. In vitro secretion of PRL in decidualized human endometrium was inhibited by the protein synthesis inhibitors, while TRH, dopamine, and bromocriptine did not have any effects on PRL secretion in incubation experiments. These data suggest that the production and secretion of PRL in the human endometrium have no relation to the presence of conceptus, and furthermore, they are regulated by mechanism different from the pituitary PRL.

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The effects of corticosterone treatment on chemical components and tubulin content were studied in the cerebrum, cerebellum and hypothalamus from male and female rats during early life.
A dual effect of corticosterone treatment was observed in the cerebellum during the course of growth. In the cerebellum from 10-day-old rats, total soluble protein, DNA, and tubulin content (mg per g wet tissue) increased in the hormone-treated male organ, but RNA, DNA, and tubulin content (mg per g wet tissue) increased in the hormone-treated female. On the other hand, the cerebellum from 20-day-old rats, RNA and tubulin content (mg per g wet tissue) and relative tubulin content (mg per g total protein) decreased in the hormone-treated male organ, but the female cerebellum exhibited a decrease in total protein and tubulin content (mg per g wet tissue), and relative tubulin content after corticosterone administration.
Only a few effects of the corticosterone treatment were observed in the cerebrum and hypothalamus from both sexes.
It is likely that corticosterone has marked effects on the cerebellum among the three brain-regions in early life, and the dual effect of the hormone in the cerebellum appears to be due to the different responsiveness in the developmental stages of nerve cells, at which the treatment was started.

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Nuclear binding sites which exhibit binding affinity similar to previously reported “Type II” sites (Clark et al., 1978) for estradiol in rat uterus were found in the liver and ventral prostate of rats and showed a binding specificity for glucocorticoid and androgen, respectively. However, both binding sites were qualitatively different from those of the rat uterus; a reducing agent, dithiothreitol, did not block the binding of steroids in the liver and ventral prostate. Extraction of the bound ligands discriminated the binding of the liver from that of the ventral prostate, Triton X-100 solubilized a majority of the bound Dex in liver nuclei, while the effect of KCl treatment was more remarkable on the bound R1881 in nuclei of the ventral prostate. Castration caused a drastic decrease in the binding of ventral prostate, only trace binding was observed at 48 h after hormone depriviation and replacement therapy restored the binding rapidly, at 3 h after testosterone injection almost 70% of the binding was detected. Although adrenalectomy did not result in a profound change in the binding sites of liver, the injection of Dex increased the number of binding sites significantly. The physiological significance of these binding sites is not clear at the present time.

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The effect of islet-activating protein (IAP) purified from culture medium of Bordetella pertussis was examined in dogs. This was assessed by the levels of pancreatic polypeptide (PP) as well as the responses of plasma insulin and glucagon to a parasympathomimetic agent, bethanechol. Plasma responses of these pancreatic hormones were measured before and 5 days after IAP injection. Although IAP had no significant effect on the bethanechol-stimulated increase in plasma glucose, insulin and glucagon, the PP response to bethanechol was significantly reduced after IAP treatment compared with that before IAP (p<0.05). In conclusion, IAP significantly and selectively reduced bethanechol-stimulated PP release in the dog although the mechanism remained to be elucidated.

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A 45-year-old woman with myxedema coma due to primary hypothyroidism manifested hyponatremia, impaired water excretion, and elevated urine osmolarity as well as natriuresis suggestive of a syndrome of inappropriate antidiuretic hormone secretion. However, plasma vasopressin was undectable or very low and plasma aldosterone levels were suppressed in the presence of hyponatremia. Subsequent replacement therapy with levothyroxine caused a rapid decline in sodium clearance which was independent of the change in glomerular filtration rate, and corrected the impaired water excretion and hyponatremia. Plasma vasopressin levels returned to the normal range after the correction of hyponatremia. Thus, the results indicate that neither vasopressin nor aldosterone plays a dominant role in the pathogenesis of the hyponatremia in this patient. It appears that thyroid hormone deficiency itself caused the derangement of tubular cell function, which resulted in the development of the impaired water excretion and hyponatremia.

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The effects of trifluoperazine on the activation of glycogenolysis by various hormones were studied in perfused rat liver. Trifluoperazine significantly inhibited glycogenolytic effect of phenylephrine and angiotensin II by lowering maximal response, and that of vesopressin by shifting the dose-response curve to the right, while α-antagonist phentolamine was inhibitory only to phenylephrine. Phosphorylase activation of phenylephrine was inhibited by trifluoperazine in parallel with glycogenolytic response. The increase in ⁴⁵Ca²⁺ efflux induced by phenylephrine, angiotensin II, and vasopressin was also inhibited by the agent. These inhibitory effects of trifluoperazine were not related to the change in tissue cyclic AMP or cyclic GMP levels. On the other hand, neither the glycogenolytic effect of glucagon, cyclic AMP, and N⁶, O²-dibutyryl cylic AMP nor phosphorylase activation by glucagon was affected by trifluoperazine. Thus, trifluoperazine specificially inhibits the activation of glycogenolysis by Ca²⁺-dependent hormones.

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Lipoprotein lipase activity of epididymal adipose tissue was measured in strepto-zotocin-induced diabetic rats. Diabetic rats of 3, 10 and 34 days duration were examined. The enzyme activity in adipose tissue of diabetic rats was similar to that of control rats of the same ages, compared on the tissue weight basis. However, since adipose tissue weight was markedly reduced in rats with both acute and chronic diabetes, total enzyme activity in the whole tissue was very low in such animals regardless of the duration of diabetes. We wish to point out that contradictory results on the adipose tissue lipoprotein lipase activity in diabetic rats in the previous reports have arisen depending on differences in the methods chosen to express enzyme activity.

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Effects of 1-(m-trifluoromethylphenyl)-piperazine, a serotonin agonist, were examined on rat plasma levels of adrenocorticotropin (ACTH) and arginine vasopressin (AVP), and on hypothalamic contents of corticotropin releasing factor (CRF) and AVP, to investigate the role of brain serotonin in ACTH regulation. Both plasma ACTH and AVP levels increased markedly 30 min after injection of the compound and were still elevated at 80 min. CRF and AVP contents in the median eminence decreased 30 min after injection but returned to the basal levels by 80 min. The AVP content in the supraoptic nucleus was elevated 80 min after injection.
The CRF and AVP content did not significantly change in the paraventricular, suprachiasmatic and arcuate nuclei. Serotonin or 1-(m-trifluoromethylphenyl)-piperazine did not stimulate the release of ACTH in pituitary cell cultures. These results suggest that both CRF and AVP were secreted into the portal vessels by 1-(mtrifluoromethylphenyl)-piperazine to release ACTH from the anterior pituitary and that both the ACTH and AVP release were stimulated via the brain serotonergic mechanism.

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The patient, a 30-year-old woman, was admitted to Itoh Hospital in February, 1979 for hyperthyroidism. She had a history of pyelonephritis and recurrent urinary tract infection. Laboratory data on admission revealed overt hyperthyroidism (T₃: 405ng/dl, T₄: 22.5μg/dl and T₃U: 57.0%), severe hypercalcemia of 12.6mg/dl and hypercalciuria. The PSP excretion and GFR were both decreased. Serum c-PTH was nondetectable. As the thyroid function improved, there was a gradual decrease and later normalization of plasma calcium, phosphate and urinary calcium excretion. When subtotal thyroidectomy was performed on October 19, 1979, hypertrophy of the parathyroid gland was not demonstrated.
In comparison with 98 other hyperthyroid patients, the pathogenesis of hypercalcemia was discussed.
In conclusion, hypercalcemia in the patient, T. Y., was regarded as a kind of disequilibrium hypercalcemia which resulted from a combination of increased bone turnover and decreased calcium excretion by the kidney.

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Anti-rat islet serum was prepared in guinea pigs by multiple subcutaneous inoculations of rat islets homogenates emulsified in complete Freund's adjuvant (CFA). The anti-rat islet serum was cytotoxic against rat spleen cells in the presence of complement and the nonspecific antibodies were absorbed with homogenates of rat livers and spleens. After absorption, the serum lost the cytotoxicity against the rat spleen cells yet showed specific cytotoxicity against the rat islet cells. The binding capacity of anti-rat islet antibody was determined by the indirect immunofluorescence test using FITC conjugated rabbit anti-guinea pig IgG serum.
As the guinea pig anti-rat islet serum contained anti-insulin antibody, the role of this antibody in this cytotoxic activity and surface immunofluorescence was studied. However, the anti-insulin antibody used as the control showed neither cytotoxicity nor surface immunofluorescence. After neutralizing the anti-insulin antibody in the antiserum with insulin, the serum remained cytotoxic to the rat islet cells and a surface immunofluorescence appeared.
These data show that specific anti-rat islet cell surface antibody can be produced in guinea pigs by multiple inoculations of rat islets homogenates with CFA.

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