Search

Objective: The purpose of this study was to determine (1) the influence of estrogen deficiency induced by gonadotropin-releasing hormone (GnRH) agonist administration on insulin sensitivity as well as hormones and factors related to insulin resistance and (2) the differences in the influence for these parameters by the degree of basal insulin sensitivity., Methods: Thirty-five women diagnosed with leiomyoma were enrolled in this study. Serum levels of fasting glucose, insulin, sex steroid hormones, sex hormone-binding globulin (SHBG), vascular inflammatory markers and cytokines before and at 6months after commencement of GnRH agonist administration were examined., Results: In all women, levels of insulin, glucose and homeostasis model assessment of insulin resistance (HOMA-IR) were not significantly changed. However, in women who had a low HOMA-IR before treatment, levels of insulin, glucose and HOMA-IR showed significant increases and total testosterone level showed a significant decrease. In women who had a high HOMA-IR, levels of insulin, HOMA-IR and SHBG were significantly decreased and levels of highly sensitive C-reactive protein, soluble intercellular adhesion molecule-1, E-selectin and monocyte chemoattractant protein-1 were significantly increased., Conclusion: Change in insulin sensitivity caused by GnRH agonist administration for premenopausal women with leiomyoma differs depending on baseline insulin sensitivity before treatment., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: The aim of the present study was to determine the effects of raloxifene on changes in circulating levels of cytokines and chemokines in relation to changes in lipid profiles and markers of inflammation in postmenopausal women., Methods: Fifty-three postmenopausal women aged 45-65 years old were randomly assigned in open, parallel-group fashion to a control group or raloxifene group. Twenty-six women received oral administration of 60 mg raloxifene every day and 27 women did not receive any drugs for 12 months. Serum cytokines levels were simultaneously measured using a multiplexed human cytokine assay., Results: Serum IL-7 concentrations in women who received raloxifene were decreased significantly (p=0.014), and serum monocyte chemoattractant protein (MCP)-1 concentrations in women who received raloxifene were decreased significantly (p=0.0003) at 12 months. In the control group, serum levels of MCP-1 and IL-7 did not show significant changes. There were significant differences (p=0.032 and p=0.0024, respectively) in percentage changes in IL-7 and MCP-1 in the control group and in the raloxifene group. Levels of low-density lipoprotein cholesterol (LDL-C) and E-selectin were decreased significantly in women who received raloxifene, but the percentage changes in LDL-C and E-selectin over a period of 12 months were not significantly correlated with percentage changes in IL-7 and MCP-1 over the same period., Conclusion: Circulating levels of IL-7 and MCP-1 decrease in postmenopausal women who received raloxifene.

The effects of Keishi-bukuryo-gan on calcitonin gene-related peptide (CGRP)-induced elevation of skin temperature were investigated in gonadotropin-releasing hormone (GnRH) analogue-treated female rats. Leupline (1.0 mg/kg) as the GnRH analogue was subcutaneously (s.c.) injected into female rats. After Keishi-bukuryo-gan (100-1,000 mg/kg, p.o.) or 17beta-estradiol (0.010 mg/kg, s.c.) was administered to GnRH analogue-treated rats for 14 days, CGRP-induced skin temperature elevation, concentration of plasma 17beta-estradiol and pituitary gonadotropin (luteinizing hormone; LH, and follicle stimulating hormone; FSH) were measured. In addition, effects of 17beta-estradiol and Keishi-bukuryo-gan on the proliferation of estrogen-dependent human breast cancer (MCF-7) cells were investigated under in vitro conditions. GnRH analogue significantly lowered the concentrations of plasma 17beta-estradiol and pituitary gonadotropins. Tissue weights of the ovaries and uterus were also decreased by the analogue. Under the condition of estrogen deficiency, intravenous (i.v.) injection of exogenous CGRP (10 microg/kg) elevated the skin temperature of the hind paws more significantly than it did in sham-treated control rats. Estrogen supplementation inhibited this elevation of skin temperature with restoration of both the lowered plasma estrogen level and the decreased uterine weight in GnRH analogue-treated rats. On the other hand, Keishi-bukuryo-gan inhibited the elevation of skin temperature in a dose-dependent manner without restoring the plasma estrogen level and uterine weight. In addition, in an in vitro study, MCF-7 cells proliferated in a dose-dependent manner by the addition of 17beta-estradiol (10(-13)-10(-8) M) to the medium. However, Keishi-bukuryo-gan (10(-6)-10(-4) mg/ml) did not activate the MCF-7 cell proliferation. These results suggest that Keishi-bukuryo-gan, which does not exhibit estrogen activity, may be useful for the treatment of hot flashes in women who are undergoing medical ovariectomy with a GnRH analogue.

The effect of Unkei-to, a traditional Japanese herbal medicine and strong in vitro releaser of cytokine-induced neutrophil chemoattractant (CINC), on the increase in locomotor activity induced by intracerebroventricular (icv) injection of corticotropin-releasing factor (CRF) in male rats in a familiar environment was investigated. Oral administration of Unkei-to (100 mg/kg) for 1 week significantly attenuated the CRF-induced increase in locomotor activity. Unkei-to also reduced the CRF-induced accumulation of hypothalamic CINC, which has a functional antagonistic action on the response to CRF; the reduction may reflect an increased release of CINC. These results suggest that Unkei-to has an alleviative effect on the action induced by brain CRF and the mechanism of this effect may partly involve CINC., (Copyright 2004 Elsevier Inc.)

Exposure to chronic stress is thought to play an important role in the etiology of depression. This disorder has been shown to involve disruption of the hypothalamo-pituitary-adrenal (HPA) system and dysfunction of the prefrontal cortex (PFC). We have demonstrated that chronic stress in rats induces similar HPA disruption or a depressive state caused by a reduction of dopaminergic and serotonergic transmission in the PFC. We have also shown that saiko-ka-ryukotsu-borei-to, a herbal medicine, prevents such chronic stress-induced HPA disruption. However, the behavioral and neurochemical bases of this drug remain unclear. Here we examined the effects of saiko-ka-ryukotsu-borei-to on the depressive behavioral state and the reduction of transmission resulting from chronic stress. The chronic stress was induced by water immersion and restraint (2 h/day) for 4 weeks followed by recovery for 10 days. The treatment with saiko-ka-ryukotsu-borei-to (100, 300, or 1000 mg/kg p.o.) ameliorated the stress-induced depressive state in a dose-dependent manner, evaluated by a rotarod test. A microdialysis study indicated that the drug treatment significantly prevented the chronic stress-induced decreases in extracellular concentrations of dopamine and serotonin in the PFC. These results suggest that saiko-ka-ryukotsu-borei-to ameliorates the chronic stress-induced depressive state based on the prevention of PFC dysfunction. These findings provide important information for treatment of depression.

Exposure to stress is known to precipitate or exacerbate many neuropsychiatric disorders such as depression. Abnormality of the neuroendocrine system, as shown by increased adrenal weight and attenuated glucocorticoid negative feedback, is frequently seen in depression. The aim of the present study is to clarify the usefulness of saiko-ka-ryukotsu-borei-to, an herbal medicine, in the treatment of abnormality of the neuroendocrine system using an experimental stress-depression model. Rats were subjected to water immersion and restraint for 2 h daily for 4 weeks (chronic stress), followed by recovery for 10 days. Saiko-ka-ryukotsu-borei-to was administered during the stress and recovery periods (100, 300, or 1000 mg/kg daily, p.o.) or only during the recovery period (1000 mg/kg). After the recovery period, the adrenal weight was measured, and glucocorticoid feedback ability was evaluated by a dexamethasone suppression test using 30 microg/kg dexamethasone. The administration of saiko-ka-ryukotsu-borei-to during the stress and recovery periods prevented the stress-induced increase in adrenal weight or the attenuated negative feedback in a dose-dependent manner. The administration of saiko-ka-ryukotsu-borei-to during the recovery period alone also ameliorated the abnormality of the neuroendocrine system. These results indicate that saiko-ka-ryukotsu-borei-to is effective against chronic stress-induced abnormality of the neuroendocrine system. Because some symptoms and symptomatic relapses in depressives are attributed to dysfunction of the hypothalamo-pituitary-adrenal axis, the present findings provide information important for prevention and treatment of depression.

Exposure to chronic stress is thought to play an important role in the etiology of depression. In this disorder, dopaminergic dysfunction in the prefrontal cortex (PFC) is thought to be involved. Indeed, chronic stress reduces dopaminergic transmission in the rat PFC or induces a behaviorally depressive state. However, a relationship between the reduced dopaminergic activity and the behavior of the chronically stressed rats has not been proven. Here, we examined the effects of local application of a dopamine Type I (D(1)) receptor-specific agonist, SKF 81297, in the PFC on the chronic-stress-induced depressive state using a rotarod test. The chronic stress produced by water immersion and restraint for 4 weeks followed by recovery for 10 days impaired the rotarod performance without changing the traction performance or locomotor activity. Although intra-PFC infusion of 1 or 10 ng of SKF 81297 did not affect this impairment, 100 ng of SKF 81297 significantly ameliorated it. These results suggest that the chronic-stress-induced depressive state is caused by a D(1) receptor-mediated hypodopaminergic mechanism in the PFC. These findings will further understanding of the mechanisms underlying the pathophysiology of depression.

To clarify the effect of mast cell-derived histamine release in the brain on anxiety, histaminergics-induced anxiety-like behaviors were examined by a light/dark test in mast cell-deficient (W/Wv) and congenitally normal (+/+) mice. In +/+ mice, when cimetidine (an H2 receptor antagonist) was coadministered with thioperamide (a neuronal histamine releaser acting via inhibition of H3 autoreceptors) or Compound 48/80 (C48/80, a selective histamine releaser from mast cells), the time spent in the light zone and the number of crossings between light and dark zones in a light/dark test decreased significantly, suggesting induction of anxiety. In W/Wv mice, however, experimental anxiety was induced by coadministration of thioperamide-cimetidine, but not C48/80-cimetidine. These results suggest that both nonneuronal mast cell-derived histamine and neuronal histamine play an important role in inducing experimental anxiety.

Exposure to chronic stress is thought to precipitate or exacerbate several neuropsychiatric disorders such as depression. Here, we examined the effects of chronic stress administered by water immersion and restraint (2 h/day) for 4 weeks followed by a 10-day recovery period on rotarod performance. The time course study revealed that the riding time on a rotating rod was not affected at Day 1 or Week 1 of the stress period, but was significantly decreased at Week 4 and after the 10-day recovery period. However, traction performance and locomotor activity were not changed by chronic stress. We next examined the involvement of a serotonergic mechanism in the impairment of rotarod performance. The post-stress administration of a serotonergic antidepressant, trazodone (10 mg/kg, daily for 10 days) significantly ameliorated the impairment of rotarod performance. A microdialysis study also revealed a decrease in the extracellular concentration of serotonin in the prefrontal cortex. These results indicate that chronic stress impairs the rotarod performance in a manner that is not due to muscle relaxation or motor dysfunction, and this impairment may imply a behaviorally depressive state mediated by a serotonergic mechanism. These findings provide insight into the underlying mechanisms of stress-induced neuropsychiatric disorders.