Objective To investigate the effect of XBXT-2 on the activity of hypothalamic-pituitary-adrenal(HPA)axis in chronic mild stress(CMS)model of rats.Methods Using ELISA to test the serum corticosterone,adrenocorticotropi...Objective To investigate the effect of XBXT-2 on the activity of hypothalamic-pituitary-adrenal(HPA)axis in chronic mild stress(CMS)model of rats.Methods Using ELISA to test the serum corticosterone,adrenocorticotropic hormone(ACTH)and corticotropin-releasing hormone(CRH)level in CMS rats;Using western blot to determine hippocampal glucocorticoids receptors(GR)expression in CMS rats.Results Co-administration of XBXT-2(25,50 mg·kg-1,p.o.,28 days,the effective doses for behavioral responses)significantly decreased the serum corticosterone and ACTH level in CMS rats,while the CRH level was not markedly affected by chronic stress or drugs.Moreover,XBXT-2 significantly increased the GR expression in the hippocampus of CMS rats.The same effects were observed in the positive control drug imipramine(10 mg·kg-1,p.o.).Conclusions The decrease of serum corticosterone and ACTH level,as well as the increase of hippocampal GR expression may be the mechanisms underlying the antidepressant action of XBXT-2,which may associate with HPA axis.展开更多
Stress adaptation is fundamental for health, and the hypothalamic-pituitary-adrenal axis (HPA) is one of its main mechanisms. Considerable data indicate that arginine vasopressin (AVP) related disturbances of stress a...Stress adaptation is fundamental for health, and the hypothalamic-pituitary-adrenal axis (HPA) is one of its main mechanisms. Considerable data indicate that arginine vasopressin (AVP) related disturbances of stress adaptation can occur with aging. However, most studies of such kind have been performed on rodents, give contradictory results and fail to consider individual characteristics of the animals. The purpose of this study was to investigate individual HPA responsiveness to acute stress and its vasopressinergic regulation in old female rhesus monkeys that differ in their behavioral responses to stress. Animals with depression-like or anxiety-like behavior (DAB) responded with higher plasma levels of ACTH and AVP, lower levels of corticosteroids and higher cortisol/DHEAS molar ratios to restraint stress and to insulin-induced hypoglycemia compared with animals with healthy adaptive behavior. AVP and ACTH dynamics were closely correlated in most animals. AVP treatment produced differences in HPA responses similar to those produced by the stressors. The ACTH response to hypoglycemic stress in the DAB animal with highest HPA responsiveness was dramatically reduced by prior administration of a V1b receptor antagonist. These results suggest that the dysfunctions of HPA observed in old animals with DAB are caused by increased tone of the vasopressinergic system in regulation of HPA stress reactivity.展开更多
Hypothalamic Corticotropin-releasing factor (CRF) directly activates the hypothalamic pituitary adrenal axis (HPA axis) during the surgical trauma induced stress response. Electroacupuncture (EA) has been demonstrated...Hypothalamic Corticotropin-releasing factor (CRF) directly activates the hypothalamic pituitary adrenal axis (HPA axis) during the surgical trauma induced stress response. Electroacupuncture (EA) has been demonstrated to have stress relieving effects in breast surgery, colorectal surgery, prostatectomy and craniotomy. This study was aimed to investigate the hypothesis that EA could regulate hypothalamic CRF in surgical trauma rats. In experiment one, Sprague-Dawley (SD) male rats were divided into intact, model (10% partial hepatectomy), sham EA and EA group. Rats from the Sham EA and EA group were stimulated at ST36-Zusanli and SP6-Sanyiniiao acupoints twice, 24 hours before the surgery and immediately after the surgery. Expressions of hypothalamic CRF and CRFR, GABA receptors, glutamate decarboxylase (GAD), serum adrenocorticotropic hormone (ACTH) and Corticosterone (CORT) were observed at 2, 4, 8 and 24 h after the surgery by radioimmunoassay (RIA), western blot, real-time PCR and immunohistochemistry. In the experiment two, SD male rats were divided into the intact, model, model + vehicle, model + L-838,417 EA and EA + L838,417 group. It was found that hypothalamus CRF, serum ACTH and CORT levels were increased in model group compared with the intact group, and those in the EA group decreased in comparison with the model group. Compared with the model group, hypothalamus-aminobutyric acid (GABA) receptor Aα3 mRNA and protein expressions of the EA group raised strikingly. In conclusion, EA alleviated surgical stress response by improving the GABA synthesis in hypothalamus, thus enhancing GABA receptors’ inhibitory regulation of the HPA axis dysfunction in rats with acute surgical trauma.展开更多
An increasing amount of evidence demonstrates the anti-aging effect of Heshouwu in pill form. In this study, a subacute aging rat model was established by continuous intraperitoneal injection of D-galactose and treate...An increasing amount of evidence demonstrates the anti-aging effect of Heshouwu in pill form. In this study, a subacute aging rat model was established by continuous intraperitoneal injection of D-galactose and treated with Heshouwu decoction (a Chinese herb for tonifying the kidney, comprising Heshouwu pill, Herba Epimedii, Radix Salviae Miltiorrhiae, and Poria). Heshouwu pill treated rats were the positive control group. Radioimmunoassay, immunohistochemical staining, and western blot assay showed hypothalamic gonadotropin-releasing hormone, hypothalamic substance P, and serum gonadotropin levels to be significantly increased in the model rats; the concentrations of hypothalamic ~3-endorphin, and serum levels of insulin-like growth factor I and testosterone were significantly decreased. 1713- and 3[3-hydroxysteroid dehydrogenase expression in testicular tissue was also decreased. Intragastric administration of Heshouwu decoction at high (9.6 g/mL/100 g), medium (4.8 g/mL/100 g), and low (2.4 g/mlJ100 g) doses, Heshouwu decoction pretreatment at a medium dose (4.8 g/mL/100 g), and Heshouwu pill (2.06 g/mL/100 g) significantly reversed these changes. Heshouwu decoction pretreatment and high-dose Heshouwu decoction had the greatest anti-aging effects. These experimental findings indicate that Heshouwu decoction can improve hypothalamic-pituitary-testicular axis secretion in a subacute aging rat model, and prevent and delay gonadal axis aging, with an effect superior to that of Heshouwu pill.展开更多
BACKGROUND: Manganese (Mn) and iron (Fe) are the primary elements of welding rods. Mn has been shown to increase prolactin (PRL) production by decreasing dopamine (DA) levels in the hypothalamus. However, Fe ...BACKGROUND: Manganese (Mn) and iron (Fe) are the primary elements of welding rods. Mn has been shown to increase prolactin (PRL) production by decreasing dopamine (DA) levels in the hypothalamus. However, Fe increases DA levels and decreases PRL levels. The toxic mechanism of Mn and Fe co-inhalation-induced regulation of the hypothalamic-hypophyseal-pituitary axis remains unclear. OBJECTIVE: To evaluate the effects of co-inhaled Mn and Fe on hypothalamic DA levels and pituitary PRL production, to investigate whether these changes are reversible, and to determine the role of co-inhaled Mn and Fe. DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment based on inhalation toxicity via whole-body exposure was performed. Hypothalamic DA levels, serum PRL, and PRL and PiN mRNA levels were analyzed at the Institute of Environmental and Occupational Medicine, Inje University, Busan, Korea, from August 2007 to May 2009. MATERIALS: MnSO4 and FeSO4 were purchased from Sigma-Aldrich, St. Louis, MO, USA. High-performance liquid chromatography (HPLC) using an electrochemical detector (ECD) was purchased from Waters Corporation, Milford, MA, USA. mRNA Capture Kit and reverse transcription-polymerase chain reaction (RT-PCR) kit were obtained from Roche Molecular Biochemicals, Mannheim, Germany and Perkin-Elmer, Wellesley, MA, USA, respectively. Rat PRL enzyme-linked immunosorbent assay kit was purchased from Biocode Hycel, Liege, Belgium. METHODS: Eighty 15-week-old, male, Fischer 344 rats were assigned to two groups: one group treated with Mn and Fe and a control group. Each group was sub-divided into four groups on the basis of treatment period (0- and 13-week treated groups with both chemicals) and recovery periods (4- and 13-week recovery groups following 13-week exposure to both chemicals). The treatment condition was 6 hours per day, 5 days per week, for the entire body. Mn and Fe co-inhalation concentrations were 1.5 mg/m3 and 3.0 mg/m3, respectively. MAIN OUTCOME MEASURES: Hypothalamic DA levels were measured using HPLC-ECD analysis mRNA levels of PRL and Pit-1 were analyzed by Northern blot hybridization and RT-PCR, respectively. Serum PRL levels were measured by enzyme-linked immunosorbent assay. RESULTS: HPLC-ECD analysis revealed that following 13-week co-inhalation of Mn and Fe, hypothalamic DA levels significantly deceased, whereas pituitary PRL mRNA, Pit-1 mRNA, and serum PRL levels significantly increased. At 4 weeks of recovery, DA level in the hypothalamic tissue was significantly increased, and PRL and Pit-1 mRNA levels in the pituitary were significantly decreased. After 13 weeks of recovery, DA and PRL levels recovered to normal. The changing pattern of serum PRL levels was in accordance with pituitary PRL mRNA levels. CONCLUSION: Subchronic co-inhalation of Mn and Fe significantly decreased hypothalamic DA levels, but induced pituitary PRL production, both of which were mediated by Pit-1. These results suggested that Mn dominates over Fe in terms of hypothalamic DA levels and pituitary PRL production, and these effects are reversible in a subchronic inhalation condition. Therefore, changes in hypothalamic DA levels and serum PRL production could be used as biomarkers for welders, who are exposed to Mn and Fe.展开更多
Anxiety disorders are among the most common of all mental disorders and their pathogenesis is a major topic in psychiatry, both for prevention and treatment. Early stressful life events and alterations of hypothalamic...Anxiety disorders are among the most common of all mental disorders and their pathogenesis is a major topic in psychiatry, both for prevention and treatment. Early stressful life events and alterations of hypothalamic pituitary adrenal(HPA) axis function seem to have a significant role in the onset of anxiety. Existing data appear to support the mediating effect of the HPA axis between childhood traumata and posttraumatic stress disorder. Findings on the HPA axis activity at baseline and after stimuli in panic disordered patients are inconclusive, even if stressful life events may have a triggering function in the development of this disorder. Data on the relationship between stress, HPA axis functioning and obsessive-compulsive disorder(OCD) are scarce and discordant, but an increased activity of the HPA axis is reported in OCD patients. Moreover, normal basal cortisol levels and hyperresponsiveness of the adrenal cortex during a psychosocial stressor are observed in social phobics. Finally,abnormal HPA axis activity has also been observed in generalized anxiety disordered patients. While several hypothesis have attempted to explain these findings over time, currently the most widely accepted theory is that early stressful life events may provoke alterations of the stress response and thus of the HPA axis, that can endure during adulthood, predisposing individuals to develop psychopathology. All theories are reviewed and the authors conclude that childhood life events and HPA abnormalities may be specifically and transnosographically related to all anxiety disorders, as well as, more broadly, to all psychiatric disorders.展开更多
Endocrine disruptors (e.g., polychlorinated biphenyls [PCBs], dichlorodiphenyl-trichloroethane [DDT], dioxin, and some pesticides) are estrogen-like and anti-androgenic chemicals in the environment. They mimic natur...Endocrine disruptors (e.g., polychlorinated biphenyls [PCBs], dichlorodiphenyl-trichloroethane [DDT], dioxin, and some pesticides) are estrogen-like and anti-androgenic chemicals in the environment. They mimic natural hormones, inhibit the action of hormones, or alter the normal regulatory function of the endocrine system and have potential hazardous effects on male reproductive axis causing infertility. Although testicular and prostate cancers, abnormal sexual development, undescended testis, chronic inflammation, Sertoli-cell-only pattern, hypospadias, altered pituitary and thyroid gland functions are also observed, the available data are insufficient to deduce worldwide conclusions. The development of intra-cytoplasmic sperm injection (ICSI) is beyond doubt the most important recent breakthrough in the treatment of male infertility, but it does not necessarily treat the cause and may inadvertently pass on adverse genetic consequences. Many well-controlled clinical studies and basic scientific discoveries in the physiology, biochemistry, and molecular and cellular biology of the male reproductive system have helped in the identification of greater numbers of men with male factor problems. Newer tools for the detection of Y-chromosome deletions have further strengthened the hypothesis that the decline in male reproductive health and fertility may be related to the presence of certain toxic chemicals in the environment. Thus the etiology, diagnosis, and treatment of male factor infertility remain a real challenge. Clinicians should always attempt to identify the etiology of a possible testicular toxicity, assess the degree of risk to the patient being evaluated for infertility, and initiate a plan to control and prevent exposure to others once an association between occupation/toxicant and infertility has been established.展开更多
As a traditional concept of Chinese medicine(CM), the theory of "Shen(Kidney) controlling bones" has been gradually proven. And in modern allopathic medicine, the multiple mechanisms of bone growth, development ...As a traditional concept of Chinese medicine(CM), the theory of "Shen(Kidney) controlling bones" has been gradually proven. And in modern allopathic medicine, the multiple mechanisms of bone growth, development and regeneration align with the theory. Shen deficiency as a pathological condition has a negative effect on the skeleton of body, specifically the disorder of bone homeostasis. Present studies indicate that Shen deficiency shares a common disorder characterized by dysfunction of hypothalamic-pituitary-adrenal(HPA) axis. HPA axis may be an important regulator of bone diseases with abnormal homeostasis. Therefore, we posit the existence of hypothalamic-pituitary-adrenal-osteo-related cells axis: cells that comprise bone tissue(osteo-related cells) are targets under the regulation of HPA axis in disorder of bone homeostasis. Chinese herbs for nourishing Shen have potential in the development of treatments for disorder of bone homeostasis.展开更多
BACKGROUND: The hippocampus regulates the hypothalamic-pituitary-adrenal axis through negative feedback. The hypothalamic paraventricular nucleus receives neuronal input from the hippocampus via the fomix, OBJECTIVE...BACKGROUND: The hippocampus regulates the hypothalamic-pituitary-adrenal axis through negative feedback. The hypothalamic paraventricular nucleus receives neuronal input from the hippocampus via the fomix, OBJECTIVE: To explore whether the negative feedback effect of the hippocampus on the hypothalamic-pituitary-adrenal axis is contributed to the inhibitory effect of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in the hippocampus on the paraventricular nucleus via the fornix. DESIGN, TIME AND SETTING: Randomized, controlled, animal experiment. The study was performed at the Department of Histology and Embryology, China Medical University between September 2006 and September 2008. MATERIALS: Rabbit anti-rat anti-MR and rabbit anti-rat anti-GR antibodies were purchased from Santa Cruz Biotechnology, USA. Rabbit anti-rat anti-corticotrophin releasing hormone (CRH) and rabbit anti-rat anti-arginine vasopressin antibodies were purchased from Wuhan Boster. METHODS: A total of 90 male, Wistar rats were randomly divided into model and sham-surgery groups (n = 45). Fornix transection was performed in the model group, while the sham-surgery group underwent surgery, but no fornix transection. MAIN OUTCOME MEASURES: Immunohistochemistry was used to examine MR and GR expression in the hippocampus, as well as CRH and anti-arginine vasopressin in the paraventricular nucleus. Western blot was used to measure alterations in MR, GR, and CRH protein expression following fomix transection. RESULTS: Compared with the sham-surgery group, there were no obvious changes in MR and GR expression in the hippocampus, or CRH and anti-arginine vasopressin expression in the paraventdcular nucleus within 4 days of fornix transection. However, after 7-10 days, significantly decreased MR and GR expression in the hippocampus, and increased CRH and anti-arginine vasopmssin expression in the paraventricular nucleus were observed (P 〈 0.05-0.01). CONCLUSION: Negative feedback from the hippocampus on the hypothalamic-pituitary-adrenal axis might be mediated through the fornix, and the corticosterene actions mediated by hippocampal corticosteroid receptors indirectly modulated the hypothalamic-pituitary-adrenal axis.展开更多
Objective:To observe the Levels of serum CORT, ACTH and CRH in SHR rats, the expression of GR, MR and CRH mRNA in hypothalamus and GR, MR mRNA in hippocampus of the ADHD model animal SHR rat, and to explore the HPA ax...Objective:To observe the Levels of serum CORT, ACTH and CRH in SHR rats, the expression of GR, MR and CRH mRNA in hypothalamus and GR, MR mRNA in hippocampus of the ADHD model animal SHR rat, and to explore the HPA axis function and related factors in SHR rats.Methods: Junior SHR rats were used as ADHD model group and WKY rats as control group. The levels of CORT, ACTH and CRH in serum were detected by ELISA, and the mRNA expressions of GR, MR, CRH in hypothalamus and GR, MR in hippocampus were detected by RT-PCR.Results:The levels of serum CORT and ACTH in SHR rats were significantly lower than those in WKY rats (P < 0.01), and the levels of serum CRH were significantly higher than those in WKY rats (P < 0.01). GR and MR mRNA expression levels in hypothalamus and hippocampus were significantly higher than those in WKY rats (P < 0.01), while CRH mRNA expression in hypothalamus was significantly lower than that in WKY rats (P < 0.01).Conclusion:The HPA axis of SHR rats showed hyporesponsiveness, which may be related to CRH priming disorder and high expression of GR and MR mRNA in hypothalamus and hippocampus.展开更多
Hypothalamic-pituitary functions in 26 cases of Turner syndrome were assessed with a combined stimulation test.The results showed that the peak GH levels of 12 cases were less than 10 μg/L; 3 patients were demonstrat...Hypothalamic-pituitary functions in 26 cases of Turner syndrome were assessed with a combined stimulation test.The results showed that the peak GH levels of 12 cases were less than 10 μg/L; 3 patients were demonstrated as having an even TSH response, while another one with a delayed TSH peak, and other 4 had high basal values and consistent exaggerated TSH responses to TRH; all patients showed increased basal and peak LH and FSH levels but 5, whose LH and FSH secretion patterns were similar to normal. 12 cases have been treated with individualized protocols and followed up for 12 months or more, of them the growth velocity all increased, especially those with hypothyroidism or with a BA less than 13. It is suggested that multiple functions of hypothalamic-pituitary axis in Turner patients be evaluated as early as possible, in order that proper treatment could be adopted and their growth and development improved.展开更多
文摘Objective To investigate the effect of XBXT-2 on the activity of hypothalamic-pituitary-adrenal(HPA)axis in chronic mild stress(CMS)model of rats.Methods Using ELISA to test the serum corticosterone,adrenocorticotropic hormone(ACTH)and corticotropin-releasing hormone(CRH)level in CMS rats;Using western blot to determine hippocampal glucocorticoids receptors(GR)expression in CMS rats.Results Co-administration of XBXT-2(25,50 mg·kg-1,p.o.,28 days,the effective doses for behavioral responses)significantly decreased the serum corticosterone and ACTH level in CMS rats,while the CRH level was not markedly affected by chronic stress or drugs.Moreover,XBXT-2 significantly increased the GR expression in the hippocampus of CMS rats.The same effects were observed in the positive control drug imipramine(10 mg·kg-1,p.o.).Conclusions The decrease of serum corticosterone and ACTH level,as well as the increase of hippocampal GR expression may be the mechanisms underlying the antidepressant action of XBXT-2,which may associate with HPA axis.
文摘Stress adaptation is fundamental for health, and the hypothalamic-pituitary-adrenal axis (HPA) is one of its main mechanisms. Considerable data indicate that arginine vasopressin (AVP) related disturbances of stress adaptation can occur with aging. However, most studies of such kind have been performed on rodents, give contradictory results and fail to consider individual characteristics of the animals. The purpose of this study was to investigate individual HPA responsiveness to acute stress and its vasopressinergic regulation in old female rhesus monkeys that differ in their behavioral responses to stress. Animals with depression-like or anxiety-like behavior (DAB) responded with higher plasma levels of ACTH and AVP, lower levels of corticosteroids and higher cortisol/DHEAS molar ratios to restraint stress and to insulin-induced hypoglycemia compared with animals with healthy adaptive behavior. AVP and ACTH dynamics were closely correlated in most animals. AVP treatment produced differences in HPA responses similar to those produced by the stressors. The ACTH response to hypoglycemic stress in the DAB animal with highest HPA responsiveness was dramatically reduced by prior administration of a V1b receptor antagonist. These results suggest that the dysfunctions of HPA observed in old animals with DAB are caused by increased tone of the vasopressinergic system in regulation of HPA stress reactivity.
文摘Hypothalamic Corticotropin-releasing factor (CRF) directly activates the hypothalamic pituitary adrenal axis (HPA axis) during the surgical trauma induced stress response. Electroacupuncture (EA) has been demonstrated to have stress relieving effects in breast surgery, colorectal surgery, prostatectomy and craniotomy. This study was aimed to investigate the hypothesis that EA could regulate hypothalamic CRF in surgical trauma rats. In experiment one, Sprague-Dawley (SD) male rats were divided into intact, model (10% partial hepatectomy), sham EA and EA group. Rats from the Sham EA and EA group were stimulated at ST36-Zusanli and SP6-Sanyiniiao acupoints twice, 24 hours before the surgery and immediately after the surgery. Expressions of hypothalamic CRF and CRFR, GABA receptors, glutamate decarboxylase (GAD), serum adrenocorticotropic hormone (ACTH) and Corticosterone (CORT) were observed at 2, 4, 8 and 24 h after the surgery by radioimmunoassay (RIA), western blot, real-time PCR and immunohistochemistry. In the experiment two, SD male rats were divided into the intact, model, model + vehicle, model + L-838,417 EA and EA + L838,417 group. It was found that hypothalamus CRF, serum ACTH and CORT levels were increased in model group compared with the intact group, and those in the EA group decreased in comparison with the model group. Compared with the model group, hypothalamus-aminobutyric acid (GABA) receptor Aα3 mRNA and protein expressions of the EA group raised strikingly. In conclusion, EA alleviated surgical stress response by improving the GABA synthesis in hypothalamus, thus enhancing GABA receptors’ inhibitory regulation of the HPA axis dysfunction in rats with acute surgical trauma.
基金supported by the Talent Introduction Fund of Hebei University, No. 2010-183the Medical Science Special Fund of Hebei University, No. 2012A1005+1 种基金the Key Project of Hebei Provincial Health Department, No. 20110151a grant from Hebei Provincial Administration of Traditional Chinese Medicine, No. 2011104
文摘An increasing amount of evidence demonstrates the anti-aging effect of Heshouwu in pill form. In this study, a subacute aging rat model was established by continuous intraperitoneal injection of D-galactose and treated with Heshouwu decoction (a Chinese herb for tonifying the kidney, comprising Heshouwu pill, Herba Epimedii, Radix Salviae Miltiorrhiae, and Poria). Heshouwu pill treated rats were the positive control group. Radioimmunoassay, immunohistochemical staining, and western blot assay showed hypothalamic gonadotropin-releasing hormone, hypothalamic substance P, and serum gonadotropin levels to be significantly increased in the model rats; the concentrations of hypothalamic ~3-endorphin, and serum levels of insulin-like growth factor I and testosterone were significantly decreased. 1713- and 3[3-hydroxysteroid dehydrogenase expression in testicular tissue was also decreased. Intragastric administration of Heshouwu decoction at high (9.6 g/mL/100 g), medium (4.8 g/mL/100 g), and low (2.4 g/mlJ100 g) doses, Heshouwu decoction pretreatment at a medium dose (4.8 g/mL/100 g), and Heshouwu pill (2.06 g/mL/100 g) significantly reversed these changes. Heshouwu decoction pretreatment and high-dose Heshouwu decoction had the greatest anti-aging effects. These experimental findings indicate that Heshouwu decoction can improve hypothalamic-pituitary-testicular axis secretion in a subacute aging rat model, and prevent and delay gonadal axis aging, with an effect superior to that of Heshouwu pill.
文摘BACKGROUND: Manganese (Mn) and iron (Fe) are the primary elements of welding rods. Mn has been shown to increase prolactin (PRL) production by decreasing dopamine (DA) levels in the hypothalamus. However, Fe increases DA levels and decreases PRL levels. The toxic mechanism of Mn and Fe co-inhalation-induced regulation of the hypothalamic-hypophyseal-pituitary axis remains unclear. OBJECTIVE: To evaluate the effects of co-inhaled Mn and Fe on hypothalamic DA levels and pituitary PRL production, to investigate whether these changes are reversible, and to determine the role of co-inhaled Mn and Fe. DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment based on inhalation toxicity via whole-body exposure was performed. Hypothalamic DA levels, serum PRL, and PRL and PiN mRNA levels were analyzed at the Institute of Environmental and Occupational Medicine, Inje University, Busan, Korea, from August 2007 to May 2009. MATERIALS: MnSO4 and FeSO4 were purchased from Sigma-Aldrich, St. Louis, MO, USA. High-performance liquid chromatography (HPLC) using an electrochemical detector (ECD) was purchased from Waters Corporation, Milford, MA, USA. mRNA Capture Kit and reverse transcription-polymerase chain reaction (RT-PCR) kit were obtained from Roche Molecular Biochemicals, Mannheim, Germany and Perkin-Elmer, Wellesley, MA, USA, respectively. Rat PRL enzyme-linked immunosorbent assay kit was purchased from Biocode Hycel, Liege, Belgium. METHODS: Eighty 15-week-old, male, Fischer 344 rats were assigned to two groups: one group treated with Mn and Fe and a control group. Each group was sub-divided into four groups on the basis of treatment period (0- and 13-week treated groups with both chemicals) and recovery periods (4- and 13-week recovery groups following 13-week exposure to both chemicals). The treatment condition was 6 hours per day, 5 days per week, for the entire body. Mn and Fe co-inhalation concentrations were 1.5 mg/m3 and 3.0 mg/m3, respectively. MAIN OUTCOME MEASURES: Hypothalamic DA levels were measured using HPLC-ECD analysis mRNA levels of PRL and Pit-1 were analyzed by Northern blot hybridization and RT-PCR, respectively. Serum PRL levels were measured by enzyme-linked immunosorbent assay. RESULTS: HPLC-ECD analysis revealed that following 13-week co-inhalation of Mn and Fe, hypothalamic DA levels significantly deceased, whereas pituitary PRL mRNA, Pit-1 mRNA, and serum PRL levels significantly increased. At 4 weeks of recovery, DA level in the hypothalamic tissue was significantly increased, and PRL and Pit-1 mRNA levels in the pituitary were significantly decreased. After 13 weeks of recovery, DA and PRL levels recovered to normal. The changing pattern of serum PRL levels was in accordance with pituitary PRL mRNA levels. CONCLUSION: Subchronic co-inhalation of Mn and Fe significantly decreased hypothalamic DA levels, but induced pituitary PRL production, both of which were mediated by Pit-1. These results suggested that Mn dominates over Fe in terms of hypothalamic DA levels and pituitary PRL production, and these effects are reversible in a subchronic inhalation condition. Therefore, changes in hypothalamic DA levels and serum PRL production could be used as biomarkers for welders, who are exposed to Mn and Fe.
文摘Anxiety disorders are among the most common of all mental disorders and their pathogenesis is a major topic in psychiatry, both for prevention and treatment. Early stressful life events and alterations of hypothalamic pituitary adrenal(HPA) axis function seem to have a significant role in the onset of anxiety. Existing data appear to support the mediating effect of the HPA axis between childhood traumata and posttraumatic stress disorder. Findings on the HPA axis activity at baseline and after stimuli in panic disordered patients are inconclusive, even if stressful life events may have a triggering function in the development of this disorder. Data on the relationship between stress, HPA axis functioning and obsessive-compulsive disorder(OCD) are scarce and discordant, but an increased activity of the HPA axis is reported in OCD patients. Moreover, normal basal cortisol levels and hyperresponsiveness of the adrenal cortex during a psychosocial stressor are observed in social phobics. Finally,abnormal HPA axis activity has also been observed in generalized anxiety disordered patients. While several hypothesis have attempted to explain these findings over time, currently the most widely accepted theory is that early stressful life events may provoke alterations of the stress response and thus of the HPA axis, that can endure during adulthood, predisposing individuals to develop psychopathology. All theories are reviewed and the authors conclude that childhood life events and HPA abnormalities may be specifically and transnosographically related to all anxiety disorders, as well as, more broadly, to all psychiatric disorders.
文摘Endocrine disruptors (e.g., polychlorinated biphenyls [PCBs], dichlorodiphenyl-trichloroethane [DDT], dioxin, and some pesticides) are estrogen-like and anti-androgenic chemicals in the environment. They mimic natural hormones, inhibit the action of hormones, or alter the normal regulatory function of the endocrine system and have potential hazardous effects on male reproductive axis causing infertility. Although testicular and prostate cancers, abnormal sexual development, undescended testis, chronic inflammation, Sertoli-cell-only pattern, hypospadias, altered pituitary and thyroid gland functions are also observed, the available data are insufficient to deduce worldwide conclusions. The development of intra-cytoplasmic sperm injection (ICSI) is beyond doubt the most important recent breakthrough in the treatment of male infertility, but it does not necessarily treat the cause and may inadvertently pass on adverse genetic consequences. Many well-controlled clinical studies and basic scientific discoveries in the physiology, biochemistry, and molecular and cellular biology of the male reproductive system have helped in the identification of greater numbers of men with male factor problems. Newer tools for the detection of Y-chromosome deletions have further strengthened the hypothesis that the decline in male reproductive health and fertility may be related to the presence of certain toxic chemicals in the environment. Thus the etiology, diagnosis, and treatment of male factor infertility remain a real challenge. Clinicians should always attempt to identify the etiology of a possible testicular toxicity, assess the degree of risk to the patient being evaluated for infertility, and initiate a plan to control and prevent exposure to others once an association between occupation/toxicant and infertility has been established.
基金Supported by the Major Science and Technology Special Project of Zhejiang Province to TONG Pei-jian(No.2014C03035)the Zhejiang Provincial Major Science and Technology Project of Medical and Health of China to TONG Pei-jian(No.201487674)Cultivation Program for Innovative Talent Graduate Students to XU Tao-tao(No.311100G00901)from Zhejiang Chinese Medical University
文摘As a traditional concept of Chinese medicine(CM), the theory of "Shen(Kidney) controlling bones" has been gradually proven. And in modern allopathic medicine, the multiple mechanisms of bone growth, development and regeneration align with the theory. Shen deficiency as a pathological condition has a negative effect on the skeleton of body, specifically the disorder of bone homeostasis. Present studies indicate that Shen deficiency shares a common disorder characterized by dysfunction of hypothalamic-pituitary-adrenal(HPA) axis. HPA axis may be an important regulator of bone diseases with abnormal homeostasis. Therefore, we posit the existence of hypothalamic-pituitary-adrenal-osteo-related cells axis: cells that comprise bone tissue(osteo-related cells) are targets under the regulation of HPA axis in disorder of bone homeostasis. Chinese herbs for nourishing Shen have potential in the development of treatments for disorder of bone homeostasis.
基金the Postdoctoral Science Foundation of China,No. 20060390301the National Natural Science Foundation of China,No.30600341the Ph.D.Program Foundation of Ministry of Education of China,No.20050159011
文摘BACKGROUND: The hippocampus regulates the hypothalamic-pituitary-adrenal axis through negative feedback. The hypothalamic paraventricular nucleus receives neuronal input from the hippocampus via the fomix, OBJECTIVE: To explore whether the negative feedback effect of the hippocampus on the hypothalamic-pituitary-adrenal axis is contributed to the inhibitory effect of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in the hippocampus on the paraventricular nucleus via the fornix. DESIGN, TIME AND SETTING: Randomized, controlled, animal experiment. The study was performed at the Department of Histology and Embryology, China Medical University between September 2006 and September 2008. MATERIALS: Rabbit anti-rat anti-MR and rabbit anti-rat anti-GR antibodies were purchased from Santa Cruz Biotechnology, USA. Rabbit anti-rat anti-corticotrophin releasing hormone (CRH) and rabbit anti-rat anti-arginine vasopressin antibodies were purchased from Wuhan Boster. METHODS: A total of 90 male, Wistar rats were randomly divided into model and sham-surgery groups (n = 45). Fornix transection was performed in the model group, while the sham-surgery group underwent surgery, but no fornix transection. MAIN OUTCOME MEASURES: Immunohistochemistry was used to examine MR and GR expression in the hippocampus, as well as CRH and anti-arginine vasopressin in the paraventricular nucleus. Western blot was used to measure alterations in MR, GR, and CRH protein expression following fomix transection. RESULTS: Compared with the sham-surgery group, there were no obvious changes in MR and GR expression in the hippocampus, or CRH and anti-arginine vasopressin expression in the paraventdcular nucleus within 4 days of fornix transection. However, after 7-10 days, significantly decreased MR and GR expression in the hippocampus, and increased CRH and anti-arginine vasopmssin expression in the paraventricular nucleus were observed (P 〈 0.05-0.01). CONCLUSION: Negative feedback from the hippocampus on the hypothalamic-pituitary-adrenal axis might be mediated through the fornix, and the corticosterene actions mediated by hippocampal corticosteroid receptors indirectly modulated the hypothalamic-pituitary-adrenal axis.
基金1.National Natural Science Foundation of China2.Yunnan Science and Technology Project.Project No:1.817608802.2017FF116-025.
文摘Objective:To observe the Levels of serum CORT, ACTH and CRH in SHR rats, the expression of GR, MR and CRH mRNA in hypothalamus and GR, MR mRNA in hippocampus of the ADHD model animal SHR rat, and to explore the HPA axis function and related factors in SHR rats.Methods: Junior SHR rats were used as ADHD model group and WKY rats as control group. The levels of CORT, ACTH and CRH in serum were detected by ELISA, and the mRNA expressions of GR, MR, CRH in hypothalamus and GR, MR in hippocampus were detected by RT-PCR.Results:The levels of serum CORT and ACTH in SHR rats were significantly lower than those in WKY rats (P < 0.01), and the levels of serum CRH were significantly higher than those in WKY rats (P < 0.01). GR and MR mRNA expression levels in hypothalamus and hippocampus were significantly higher than those in WKY rats (P < 0.01), while CRH mRNA expression in hypothalamus was significantly lower than that in WKY rats (P < 0.01).Conclusion:The HPA axis of SHR rats showed hyporesponsiveness, which may be related to CRH priming disorder and high expression of GR and MR mRNA in hypothalamus and hippocampus.
文摘Hypothalamic-pituitary functions in 26 cases of Turner syndrome were assessed with a combined stimulation test.The results showed that the peak GH levels of 12 cases were less than 10 μg/L; 3 patients were demonstrated as having an even TSH response, while another one with a delayed TSH peak, and other 4 had high basal values and consistent exaggerated TSH responses to TRH; all patients showed increased basal and peak LH and FSH levels but 5, whose LH and FSH secretion patterns were similar to normal. 12 cases have been treated with individualized protocols and followed up for 12 months or more, of them the growth velocity all increased, especially those with hypothyroidism or with a BA less than 13. It is suggested that multiple functions of hypothalamic-pituitary axis in Turner patients be evaluated as early as possible, in order that proper treatment could be adopted and their growth and development improved.