Nihon Naibunpi Gakkai zasshi最新文献

Nitric oxide (NO), a simple gas with free radical chemical properties, is synthesized by nitric oxide synthase (NOS) from arginine in neurons and acts as a neurotransmitter in the central and peripheral nervous systems. The immunohistochemical demonstration of NOS-immunoreactivity and its histochemical marker, NADPH-diaphorase activity in many neurons of the hypothalamus, suggest that NO plays a role in controlling the production and/or release of hypothalamic neuroendocrine peptides. In the present study, the expression of NOS in the enkephalin and dynorphin systems of the rat hypothalamus was examined by the combined method of the NADPH-diaphorase histochemistry and the immunocytochemistry of methionine enkephalin (M-Enk) or dynorphin B (Dyn-B). About 6 to 9% of M-Enk immunoreactive neurons in the paraventricular, arcuate and ventromedial nuclei expressed NADPH-diaphorase activity. Dyn-B immunoreactive neurons, however, showed NADPH-diaphorase activity in high ratio (37%-84%) in the supraoptic nucleus and the parvocellular and magnocellular paraventricular nucleus. These results revealed that a part of the enkephalin and dynorphin neurons in the rat hypothalamus have the ability to produce NO. The high ratio of expression of NO in magnocellular neurosecretory dynorphin containing neurons suggested that NO participates in controlling posterior pituitary hormone secretion together with dynorphin.

Progesterone receptor is unique in terms of the existence of two isoforms of A and B. The isoforms are expressed by two distinct promoters in the peripheral as well as the brain. The 5'-untranslated region and the coding region around ATG 1 of rat progesterone receptor form B as well as the ligand binding domain are cloned. The function of the forms A and B is still unclear. However, it has been reported that the form A is a hormone-dependent transdominant repressor of the B function under certain circumstance of the cell. This model is very interesting to elucidate the molecular mechanism of progesterone action.

The effects of GnRH agonist (buserelin) on in vitro ovarian steroidogenesis were studied using DES-treated immature rats and PMS-treated immature rats. The estradiol and progesterone secreted by the cultured ovarian cells and the activities of various enzymes of steroid-metabolism were examined with or without gonadotropins (FSH or hCG), and the effects of 10(-6)-10(-12) M of buserelin on those indices were observed for 3-72 hours. In addition, the kinetic study of ovarian GnRH receptor was performed using 125I-labelled buserelin and crude ovarian cell membrane fraction of PMS-treated rats. The Scatchard analysis revealed the specific high affinity and low capacity ovarian GnRH receptor (Kd = 0.92 nM and Bmax = 0.57 fmol/mg tissue). The FSH-stimulated cholesterol side chain cleavage enzyme (CSCC) activity of the DES-treated rats was suppressed in a dose-dependent manner by buserelin. Estradiol release and aromatase activity were increased by 10(-8) M buserelin within 48 hours from the beginning of the incubation of the PMS-treated rat ovarian cells, but were suppressed after 48 hours. Buserelin increased basal progesterone secretion and both activities of CSCC and of 3 beta-hydroxysteroid dehydrogenase of PMS-treated rat ovarian cells incubated without hCG, which were suppressed by buserelin co-incubated with 100 IU/ml of hCG. These results suggested that GnRH plays a physiological role in ovarian steroidogenesis binding the specific receptor and that GnRH promotes the development of the follicle through increased estrogen synthesis in the early stage of the folliculogenesis and the luteinization in the late stage of the follicular development through increased progesterone and decreased estradiol production and the luteolysis in the luteinized cells by hCG through decreased progesterone secretion.

A 50-year-old man was admitted to our hospital for the evaluation of hypocalcemia and the treatment of diabetes mellitus. Seven months before admission, he sometimes felt thirst and polyuria, and 4 months before admission, he went to a doctor to check his blood glucose and was diagnosed as having diabetes mellitus which had suddenly developed. At that time he was treated with sulfonylurea, but his diabetic control was very poor. At the time of admission to our hospital, the patient's serum calcium (Ca) level was 5.7 mg/dl, phosphorus (P) 5.0 mg/dl, and fasting blood glucose 308 mg/dl, but urinary ketone bodies were not detected. High sensitive assay of parathyroid hormone (HS-PTH), intact PTH and C-terminus PTH concentrations were under the level of detection. TSH level was slightly high (6.1 mu U/ml) with positive antimicrosomal and antithyroglobulin antibodies but thyroid hormone levels were within normal limits. TRH test showed over-response of TSH. Based on Ellsworth-Howard test, we made the diagnosis of idiopathic hypoparathyroidism associated with primary hypothyroidism and diabetes mellitus. He was treated with insulin twice a day and reached good control, and he was also administered 1 alpha-OH-D3 and calcium lactate resulting in an increase of serum Ca level after 2 weeks. These findings suggest that this case may be a polyglandular autoimmune (PGA) syndrome type 1 reported by Neufeld, which is very rare in Japan. The type of diabetes mellitus of this case is controversial. It is, however, necessary to pay attention to the decrease of the patient's insulin-secreting activity because autoimmune disorders are accompanied by this case.

Insulin antibodies (IA) are detectable in the sera of most insulin-treated patients with diabetes mellitus. Antibodies to exogenous insulin sometimes cause clinical symptoms of insulin resistance, allergy, and local lipoatrophy. Although the frequency of these complications has diminished with the use of highly purified porcine insulin or recombinant human insulin, there are some patients with high titer of IA. Autoantibodies to insulin (IAA) are also described. IAA has been reported to be in association with both insulin-dependent diabetes mellitus (IDDM) and polyendocrine autoimmune disease. For many years these antibodies have been measured by radiobinding assay (RBA) in which the complexes are precipitated non-specifically by polyethylene glycol. In the present study we developed a rapid and quantitative enzyme-linked immunosorbent assay (ELISA) method for measuring IA and IAA using recombinant human insulin antigen. We applied this method to the samples obtained from patients with diabetes mellitus and autoimmune thyroid disease and then compared the results with those obtained from the RBA method. The calibration curve for ELISA was derived from the dilution curve of a single serum from a patient positive for insulin antibody, and the results were expressed arbitrarily as ELISA UNIT. The calibration curve was approximately linear on the log-log scale within the range of 0.1-2.0 at optical density (OD)450nm, (6.25-200 ELISA UNIT). The intra-assay (CV = 2.3-3.1%) and inter-assay (CV = 2.8-7.2%) precisions were acceptable. Recovery rate varied from 74.5% to 118.5% and dilution experiments showed good linearity. Specificity was demonstrated by substituting purified human IgG for the test serum and glucagon for insulin. Except for hemoglobin, coexisting substances in serum had almost no effect on ELISA. The range of ELISA UNIT (Mean +/- SD) of 83 normal sera was 12.7 +/- 4.6. Positivity for IA by ELISA (> normal Mean + 3SD) was 11 out of 58 (19.0%) and 26 out of 55 (47.3%) in patients with IDDM and with non-insulin-dependent diabetes mellitus (NIDDM) who were treated with insulin, respectively. Positivity for IAA by ELISA was 5 out of 173 (2.8%) and 1 out of 20 (5.0%) in patients with NIDDM without insulin therapy and hyperthyroidism due to Graves' disease, respectively. However, by RBA, we detected 4 other cases positive for IAA in NIDDM without insulin therapy and one case in Graves' disease. The present study demonstrates that the newly developed method of ELISA using recombinant human insulin antigen is clinically useful for measuring IA and IAA.

Thyroid function has been almost exactly evaluated by the measurement of serum free thyroxine (FT4), free triiodothyronine (FT3) and thyrotropin (TSH) concentrations. However, we occasionally experience patients who show a discrepancy between free thyroid hormones and TSH values, and the assessment of thyroid function in such cases is extremely difficult. Thyroid hormone autoantibodies (THAA) interfere with radioimmunoassay (RIA) of FT4 and FT3 by giving inappropriate values. To investigate the incidence of THAA, immune precipitation of patients' sera after incubation with labelled T4 (125I-T4) or T3 (125I-T3) analog tracer was done in 394 patients with thyroid diseases. 9 patients (2.3%) showed an increased binding of 125I-T4 or 125I-T3 analog. Heterophilic antimouse antibodies in a patient's serum (human antimouse immunoglobulin antibodies: HAMA) can interfere in two-site immunometric assays (IMA) using mouse monoclonal antibodies and result in spuriously increased serum TSH concentrations. Manufacturers now customarily add nonspecific mouse immunoglobulins into their assay kits to absorb HAMA and prevent such interference. This approach may not always be enough to prevent HAMA interference in all samples. In 14 thyrotoxic patients with inappropriately high TSH measured by an IMA kit, we measured the levels of TSH by the further addition of mouse serum into this kit. Their serum TSH levels were fully suppressed except for 2 patients with a syndrome of inappropriate secretion of TSH (SITSH). The presence of abnormal albumin in the serum also interferes with RIA of FT4 and FT3. We experienced a female case of Graves' disease treated with methimazole who showed an inappropriately high serum FT3 measured by an analog tracer RIA kit, whose serum FT4, FT3 and TSH were 1.31 ng/dl, 19.3 pg/ml and 1.9 mu U/ml respectively. Although the anti-T3 autoantibody was considered to be present initially, immune precipitation of her serum with 125I-T3 analog tracer gave a negative result. In order to elucidate this finding, Sephadex-G200 chromatography of her serum after incubation with 125I-T3 analog tracer was done. Radioactivity of her serum in albumin fraction was significantly higher than that of normal control serum to indicate the presence of abnormal albumin in the serum. In conclusion, to assess the thyroid function of a patient with a discrepancy between free thyroid hormones and TSH values, it is important to consider the presence of THAA, HAMA, or rarely, an abnormal albumin.

It is well known that serum IGF-I concentrations are regulated endocrinologically since IGF-I has a growth-promoting action as a mediator of growth hormone. However, recent reports suggest that nutritional states influence serum IGF-I concentration because IGF-I shows anabolic effects like insulin. The aim of this study was to clarify the influences of maternal nutritional states or metabolism on the IGF-I concentrations in normal and abnormal pregnancy. In normal pregnant women, a significant positive correlation was indicated between serum IGF-I concentrations and maternal weight gain during pregnancy or serum triglyceride levels, and a significant negative correlation was observed between serum IGF-I concentrations and serum total protein levels. In the cases complicated with hyperemesis or hyperthyroidism during early gestation, a marked reduction of maternal body weight was observed, and serum IGF-I concentration was extremely low compared with that in normal pregnant women, but serum IGF-I levels gradually increased as the maternal body weight recovered after treatment by intravenous hyperalimentation or an anti-thyroid drug. In cases of severe toxemia of pregnancy, maternal weight gain and serum triglyceride levels were markedly increased, but serum IGF-I levels were significantly lower compared with those in normal pregnant women in the same gestational age. In severe toxemia of pregnancy, there was no significant correlation between serum IGF-I levels and maternal weight gain or serum triglyceride levels, and these results may be influenced by such abnormalities as water retention, hemoconcentration, severe hypoproteinemia and severe negative nitrogen balance not found in normal pregnancy. In conclusion, it is considered that IGF-I concentration is regulated not only by endocrinological factors, but also by metabolic factors in maternal circulation during pregnancy, and the measurement of maternal IGF-I concentration seems to be a useful parameter to evaluate the maternal nutritional states.

A 41-year-old man was admitted to our hospital because of general fatigue, sexual debility and finger stiffness. Endocrinological examinations revealed that he had panhypopituitarism, resulting in secondary adrenal insufficiency, hypothyroidism and gonadal failure. Computed tomography (CT) of the head demonstrated a low density intrasellar mass, while brain magnetic resonance imaging (MRI) showed a high intensity mass extending from the intrasellar to suprasellar region in both T1WI and T2WI. The mass was removed by transsphenoidal surgery and histologically diagnosed as Rathke's cleft cyst. Replacement with hydrocortisone and levothyroxine sodium greatly improved the clinical symptoms. Rathke's cleft cyst causing panhypopituitarism is relatively rare. The clinical and endocrinological characteristics of Rathke's cleft cyst were discussed based on the findings in 49 Japanese cases including this case and two other cases we have experienced.

Hyporeninemic hypoaldosteronism has mainly been described in patients with diabetes mellitus. In order to elucidate the mechanisms of hyporeninemia in diabetic patients, the author studied the response of active renin concentration (ARC) and inactive renin concentration (IRC) to the administration of captopril or sodium depletion in patients with diabetes mellitus and glomerulonephritis and in normal subjects. The diabetic patients were separated into four groups: Group 0, diabetic patients without neuropathy or nephropathy; Group I, those with neuropathy without nephropathy; Group II, those without neuropathy with nephropathy; Group III, those with neuropathy and nephropathy. Diabetic patients with some complications had slightly lower plasma active renin levels than those without complications. The mean increase in plasma active renin after captopril (delta ARC) and sodium depletion was lower in group I than in group 0, and there was no difference between group II and group 0. There was no correlation between delta ARC and creatinine clearance (Ccr) in diabetes mellitus. Plasma prorenin was higher in group I than in group 0, and there was no difference between group II and group 0. No significant change of prorenin after captopril was observed in all groups, but the mean increase in plasma inactive renin after sodium depletion was slightly higher in groups I and III than in groups 0 and II. ARC/IRC was significantly lower in group I than in group 0, and there was no difference between group II and group 0. There was no correlation between ARC/IRC and Ccr in diabetes mellitus, but significant correlation between ARC/IRC and postural change in systolic blood pressure. In three diabetic patients with hyporeninemic hypoaldosteronism, the postural fall in systolic blood pressure was significant, and ARC/IRC was significantly low, but IRC was not high. These results suggest that autonomic dysfunction is a major factor in an impairment of the processing of prorenin to active renin in diabetic patients, and severe autonomic dysfunction may impair the biosynthesis of prorenin in patients with hyporeninemic hypoaldosteronism.