AIM： To investigate the effect and mechanism of electro-acupuncture lEA） at ST25 and ST37 on irritable bowel syndrome （IBS） of rats. METHODS： A total of 21 male Sprague-Dawley rats were randomly divided into norm...AIM： To investigate the effect and mechanism of electro-acupuncture lEA） at ST25 and ST37 on irritable bowel syndrome （IBS） of rats. METHODS： A total of 21 male Sprague-Dawley rats were randomly divided into normal group, model group and EA group. A rat model of IBS was established by constraining the limbs and distending the colorectum of rats. Rats in EA group received bilateral EA at ST25 and ST37 with a sparse and intense waveform at a frequency of 2/50 Hz for 15 min, once a day for 7 d as a course. Rats in normal and model groups were stimulated by distending colorectum （CR）. An abdominal withdrawal reflex （AWR） scoring system was used to evaluate improvements in visceral hypersensitivity. Toluidine blue-improved method, immunohistochemistry and radioimmunoassay were used to observe mucosal mast cells （MC）, changes of substance P （SP） and substance P receptor （SPR） in colon and change of corticotropin-releasing hormone （CRH） in hypothalamus. RESULTS： The threshold of visceral sense was significantly lower in model group than in normal group,and significantly higher in EA group than in model group. The number of mucosal MC was greater in model group than in normal group and significantly smaller in EA group than in model group. The CRH level in hypothalamus of rats was significantly higher in model group than in normal group, which was remarkably decreased after electro-acupuncture treatment. The SP and SPR expression in colon of rats in model group was decreased after electro-acupuncture treatment. CONCLUSION： EA at ST25 and ST37 can decrease the number of mucosal MC and down-regulate the expression of CRH in hypothalamus, and the expression of SP and SPR in colon of rats with IBS.展开更多
Disordered signalling between the brain and the gut are generally accepted to underlie the functional bowel disorder, irritable bowel syndrome(IBS). However, partly due to the lack of disease-defining biomarkers, unde...Disordered signalling between the brain and the gut are generally accepted to underlie the functional bowel disorder, irritable bowel syndrome(IBS). However, partly due to the lack of disease-defining biomarkers, understanding the aetiology of this complex and multifactorial disease remains elusive. This common gastrointestinal disorder is characterised by alterations in bowel habit such as diarrhoea and/or constipation, bloating and abdominal pain, and symptom exacerbation has been linked with periods of stress, both psychosocial and infection-related. Indeed, a high level of comorbidity exists between IBS and stress-related mood disorders such as anxiety and depression. Moreover, studies have observed alterations in autonomic output and neuro-endocrine signalling in IBS patients. Accumulating evidence indicates that a maladaptive stress response, probably mediated by the stress hormone, corticotropin-releasing factor contributes to the initiation, persistence and severity of symptom flares.Other risk factors for developing IBS include a positive family history, childhood trauma, dietary factors and prior gastrointestinal infection. An emerging role has been attributed to the importance of immune factors in the pathophysiology of IBS with evidence of altered cytokine profiles and increased levels of mucosal immune cells. These factors have also been shown to have direct effects on neural signalling. This review discusses how pathological changes in neural, immune and endocrine pathways, and communication between these systems, contribute to symptom flares in IBS.展开更多
AIM: To investigate the effect of electroacupuncture on corticotropin-releasing hormone(CRH) in the colon, spinal cord, and hypothalamus of rats with chronic visceral hypersensitivity.METHODS: A rat model of chronic v...AIM: To investigate the effect of electroacupuncture on corticotropin-releasing hormone(CRH) in the colon, spinal cord, and hypothalamus of rats with chronic visceral hypersensitivity.METHODS: A rat model of chronic visceral hypersensitivity was generated according to the internationally accepted method of colorectal balloon dilatation. In the 7th week after the procedure, rats were randomly divided into a model group(MG), electroacupuncture group(EA), and sham electroacupuncture group(S-EA). After treatment, the abdominal withdrawal reflex(AWR) score was used to assess the behavioral response of visceral hyperalgesia. Immunohistochemistry(En Vision method), ELISA, and fluorescence quantitative PCR methods were applied to detect the expression of CRH protein and m RNA in the colon, spinal cord, and hypothalamus.RESULTS: The sensitivity of the rats to the colorectal distension stimulus applied at different strengths(20-80 mm Hg) increased with increasing stimulus strength, resulting in increasing AWR scores in each group. Compared with NG, the AWR score of MG was significantly increased(P < 0.01). After conducting EA, the AWR scores of the rats were decreased compared with MG rats. The relative expression of CRH m RNA in the colon, spinal cord, and hypothalamus of MG rats was significantly increased compared with NG rats(P < 0.01). CRH m RNA in the colon and spinal cord of EA and S-EA rats was decreased to varying degrees(P > 0.05) compared with normal rats(NG). However, the decrease in EA compared with MG rats was statistically significant(P < 0.01). The average optical density of CRH expression in the colon of the MG rats was significantly enhanced compared with NG(P < 0.05), while the average optical density of CRH expression in the EA and S-EA rats was significantly decreased compared with MG rats(P < 0.01, P < 0.05, respectively). Compared with MG rats, the CRH concentration in the spinal cord of EA rats was significantly reduced(P < 0.01), but there was no significant change in S-EA rats(P > 0.05).CONCLUSION展开更多
AIM To explore the significance of corticotropin-releasing hormone(CRH)-receptor(R)2 in mucosal healing of dextran sulfate sodium(DSS)-induced colitis and the effect of Tong-Xie-Yao-Fang(TXYF) on CRH-R2 expression and...AIM To explore the significance of corticotropin-releasing hormone(CRH)-receptor(R)2 in mucosal healing of dextran sulfate sodium(DSS)-induced colitis and the effect of Tong-Xie-Yao-Fang(TXYF) on CRH-R2 expression and regulation.METHODS Ulcerative colitis was induced in mice by administration of 3%(w/v) DSS for 7 d. Once the model was established,mice were administered urocortin-2(30 μg/kg), a peptide which binds exclusively to CRH-R2, or various doses of aqueous TXYF extracts(2.8-11.2 g/kg), a CRH-R2 antagonist Astressin(Ast)2B(20 μg/kg), Ast2B + Ucn2, or Ast2B with various doses of aqueous TXYF extracts for 9 d. Colonic mucosal permeability was then evaluated by measuring the fluorescence intensity in serum. The colitis disease activity index(DAI), histology, body weight loss and colon length were assessed to evaluate the condition of colitis. Terminal deoxynucleotidyl transferase d UTP nick-end labeling was used to detect apoptosis of the intestinal epithelial cells. The expression level of Ki-67 represented the proliferation of colonic epithelial cells and was detected by immunohistochemistry. The expression levels of inflammation cytokines IL-6, TNF-α and CXCL-1 were examined in colon tissues using real-time PCR and ELISA kits.RESULTS Compared with the DSS group, mice treated with the CRH-R2 antagonist Ast2B showed greater loss of body weight, shorter colon lengths(4.90 ± 0.32 vs 6.21 ± 0.34 cm, P < 0.05), and higher DAI(3.61 ± 0.53 vs 2.42 ± 0.32, P < 0.05) and histological scores(11.50 ± 1.05 vs 8.33 ± 1.03, P < 0.05). Additionally, the Ast2B group showed increased intestinal permeability(2.76 ± 0.11 μg/mL vs 1.47 ± 0.11 μg/mL, P < 0.001), improved secretion of inflammatory cytokines in colon tissue, and reduced colonic epithelial cell proliferation(4.97 ± 4.25 vs 22.51 ± 8.22, P < 0.05). Increased apoptosis(1422.39 ± 90.71 vs 983.01 ± 98.17, P < 0.001) was also demonstrated. The Ucn2 group demonstrated lower DAI(0.87 ± 0.55 vs 2.42 ± 0.32, P < 0.001) and histological scores(4.33 ± 1.50展开更多
In trauma, infection and hemorrhagic shock derived stress, primary and secondary injury may result in severe derangement in the internal environment. The abnormal changes of immune-mediated inflammation interfere its ...In trauma, infection and hemorrhagic shock derived stress, primary and secondary injury may result in severe derangement in the internal environment. The abnormal changes of immune-mediated inflammation interfere its pathogenesis and development directly. In recent years, various aspects of neuroendocrine responses, especially the regulatory effects of hypothalamic-pituitary-adrenal and sympathetico-adrenomedullary axes in inflammatory diseases have been the focus of research. Most importantly,corticotropin-releasing hormone （CRH） acts as a key player in the regulation of interactions between neuroendocrine and immunity both directly and indirectly. The paper summarized the recent development of CRH in the immune-mediated inflammation.展开更多
Objective To investigate the mechanisms through which kidney-tonifying herbs（KTHs） and liver-clearing herbs（LCHs） in Dingjing Decoction（DJD） regulate premature ovarian failure（POF）. Methods One hundred and fif...Objective To investigate the mechanisms through which kidney-tonifying herbs（KTHs） and liver-clearing herbs（LCHs） in Dingjing Decoction（DJD） regulate premature ovarian failure（POF）. Methods One hundred and fifty Sprague-Dawley rats were randomly divided into five groups such as control, model, KTHs, LCHs, and DJD groups. POF-related biological molecules were examined. Factor analysis was performed to investigate the regulatory networks and key biomolecules involved in mediating POF after treatment with KTHs and LCHs. Results The master regulatory factors in the reproductive endocrine network associated with KTHs intervention included four molecules in the pituitary-ovarian axis, cortisol（CORT） in the target gland of pituitary-adrenal axis, and some molecules in the hypothalamus. In contrast, the master regulatory factors associated with LCHs intervention included four molecules in the pituitary-ovarian axis and some molecules in the hypothalamus; No biomolecules in the pituitary-adrenal axis were involved in the LCH-mediated mechanisms.Gonadotropin-releasing hormone（Gn RH）, which was identified as a common biological molecule in the hypothalamus, was involved in regulating the reproductive endocrine network in association with KTHs intervention. Conclusion KTHs directly regulates biological molecules in the pituitary-adrenal axis and indirectly regulates those in the pituitary-adrenal axis through the hypothalamus, while the LCHs only exert its effects indirectly. Gn RH is the key biological molecule associated with KTHs intervention.展开更多
OBJECTIVE: To investigate whether electroacupuncture(EA) at bilateral Tianshu(ST25) and Zusanli(ST36) acupoints could alleviate stress-induced irritable bowel syndrome(IBS) and evaluate its effect on gut microbiota an...OBJECTIVE: To investigate whether electroacupuncture(EA) at bilateral Tianshu(ST25) and Zusanli(ST36) acupoints could alleviate stress-induced irritable bowel syndrome(IBS) and evaluate its effect on gut microbiota and corticotropin-releasing factor(CRF). METHODS: Thirty C57BL/6 mice were randomly divided into the normal, water avoidance stress(WAS), and WAS+EA groups(10 mice per group). An experimental model of IBS was established by exposing the animals to WAS. The mice were treated with EA at the bilateral Tianshu(ST25) and Zusanli(ST36) acupoints. The abdominal withdrawal reflex test was conducted to evaluate visceral sensitivity in IBS. Gut microbiota was analyzed using 16S r RNA sequencing and analysis. The expression of CRF was determined using immuneofluorescence and quantitative real-time polymerase chain reaction. RESULTS: EA alleviated visceral hypersensitivity in a mouse model of WAS-induced IBS. It modulated the dysbiosis of gut microbiota induced by WAS. Moreover, it suppressed the WAS-induced overexpression of CRF in colon tissues. CONCLUSION: The findings of this study suggest that EA alleviated WAS-induced IBS via mechanisms possibly involving the modulation of the dysbiosis of gut microbiota and suppression of CRF expression.展开更多
Objective Corticotropin-releasing hormone（CRH）plays an important role in neuroendocrine,autonomic and behavioral responses to stressors.In the present study,the effect of chronic unpredictable mild stress（CUMS）on ...Objective Corticotropin-releasing hormone（CRH）plays an important role in neuroendocrine,autonomic and behavioral responses to stressors.In the present study,the effect of chronic unpredictable mild stress（CUMS）on CRH neurons was investigated in rat brain.Methods The rats were exposed to one of the stressors each day for 21 d.Immunostaining was performed to detect the CRH-positive neurons in the paraventricular nucleus（PVN）of the hypothalamus and in amygdala.Results After the stress protocol,the animals showed a reduction in body weight gain as well as reduced sucrose preference and locomotor activity.Interestingly,the CRH neurons in both PVN and central nucleus of the amygdala（CeA）were stimulated by CUMS.The densities of CRH-containing neurons in both PVN and CeA were significantly higher than those in control group.Conclusion The CRH systems in PVN and CeA may both contribute to depression-like behaviors during CUMS.展开更多
AIM: To assess corticotropin-releasing factor receptor 2 (CRF 2 ) expression in the colon of healthy subjects and patients with ulcerative colitis (UC). METHODS: We examined CRF2 gene and protein expression in the dis...AIM: To assess corticotropin-releasing factor receptor 2 (CRF 2 ) expression in the colon of healthy subjects and patients with ulcerative colitis (UC). METHODS: We examined CRF2 gene and protein expression in the distal/sigmoid colonic mucosal biopsies from healthy subjects and patients with UC (active or disease in remission), human immunodeficiency virus (HIV) and functional bowel disease (FBD) by reverse transcriptionpolymerase chain reaction and immunofluorescence. RESULTS: Gene expression of CRF2 was demonstrated in the normal human colonic biopsies, but not in the human colorectal adenocarcinoma cell line Caco2. Receptor protein localization showed immunoreactive CRF 2 receptors in the lamina propria and in the epithelial cells of the distal/sigmoid biopsy samples. Interestingly, CRF 2 immunoreactivity was no longer observed in epithelial cells of patients with mild-moderately active UC and disease in remission, while receptor protein expression did not change in the lamina propria. No differences in CRF 2 expression profile were observed in distal/sigmoid intestinal biopsies from HIV infection and FBD patients, showing no signs of inflammation. CONCLUSION: The down-regulation of the CRF2 receptor in the distal/sigmoid biopsies of UC patients is indicative of change in CRF 2 signalling associated with the process of inflammation.展开更多
The activities of corticotropin-releasing factor(CRF) and related peptides are mediated a number of receptors with seven transmembrane domains that are coupled to the Gs and Gq proteins. These receptors are known as C...The activities of corticotropin-releasing factor(CRF) and related peptides are mediated a number of receptors with seven transmembrane domains that are coupled to the Gs and Gq proteins. These receptors are known as CRF-Rs. In vitro studies have evidenced that urocortin(UCN) and CRF provoke an increase in the contractility of the uterus which is induced by endometrial prostaglandin F2 a. Furthermore, through trophoblasts, it stimulates the secretion of adrenocorticotropic hormone(ACTH) and prostaglandin PGE2 and has a vasodilatory effect on the placenta. While it is well known that the placenta produces considerable quantities of CRF, several studies have, however, excluded that the placenta can generate significant quantities of UCN. In the short term, the human fetal adrenal gland produces more cortisol and dehydroepiandrosterone sulfate. The gestational tissues express UCN3 and UCN2 m RNA in cytotrophoblast and syncytiotrophoblast cells, while UCN2 is only to be found in the maternal and fetal vessels and amniotic cells. Nevertheless, gestational tissues express UCN2 and UCN3 differentially and do not stimulate placental ACTH secretion. In term pregnancies, maternal plasma levels of CRF and UCN are lower than at the beginning of pregnancy and are correlated to labor onset. Conversely,they do not decrease in post-term pregnancies. This evidence would seem to indicate that the fine-regulated expression of these neuropeptides is important in determining the duration of human gestation. In this scenario, low concentrations of UCN in the amniotic fluid at mid-term may be considered a sign of predisposition to preterm birth.展开更多
Objective： To observe the effect of moxibustion on the protein and mRNA expressions of corticotropin-releasing factor （CRF） and corticotropin-releasing factor receptor 2 （CRFR1） in hypothalamus of trinitrobenzene...Objective： To observe the effect of moxibustion on the protein and mRNA expressions of corticotropin-releasing factor （CRF） and corticotropin-releasing factor receptor 2 （CRFR1） in hypothalamus of trinitrobenzene sulfonic acid （TNBS）-induced experimental colitis rats, and to explore the central mechanisms of moxibustion in improving visceral pain and the pain-related emotions in experimental colitis rats. Methods： Thirty-six Sprague-Dawley （SD） rats were randomly divided into a normal group （NG）, a model group （MG）, a herb-partitioned moxibustion group （HPMG） and a sham herb-partitioned moxibustion group （SHPMG）. Except the NG, rats in the remaining three groups all received TNBS enema to establish experimental colitis models. The HPMG received herb-partitioned moxibustion （HPM） at bilateral Tianshu （ST 25） and Qihai （CV 6） for intervention; for the SHPMG, the herbal cakes and moxa cones were only placed on the acupoints but not ignited; rats in the MG and NG were only fixed in the same way as those in the HPMG but did not receive any treatment. At the end of the intervention, the abdominal withdrawal reflex （AWR） score, the open field test （OFT） score and the elevated plus maze （EPM） score were observed to measure the changes in visceral pain and pain-related emotions of the rats. The enzyme-linked immunosorbent assay （ELISA） was used to examine the expressions of CRF and CRFR1 proteins in hypothalamus; the fluorescence-based quantitative polymerase chain reaction （PCR） was used to detect the expressions of CRF and CRFR1 mRNAs in hypothalamus. Results： Compared with the NG, the AWR score increased significantly and the OFT and EPM scores dropped significantly in the MG （all P〈0.05）, and the expressions of hypothalamic CRF and CRFR1 proteins and mRNAs increased significantly （all P〈0.01）. Compared with the MG and SHPMG, the AWR score dropped significantly and the OFT and EPM scores increased significantly in the HPMG （all P〈0.01展开更多
Objective： To explore the changes of Treg-Thl 7 balance influenced by corticosterone, major ef- fect hormone ofhypothalamic-pituitary-adrenal （HPA） axis under running stress. Methods： Atotal of 25 corticotropin-r...Objective： To explore the changes of Treg-Thl 7 balance influenced by corticosterone, major ef- fect hormone ofhypothalamic-pituitary-adrenal （HPA） axis under running stress. Methods： Atotal of 25 corticotropin-releasing hor- mone （CRH） wildtype （CRH＋/＋） and knockout （CRH-/-） mice were adopt and divided into 4 groups as follows： CRH＋/＋ ctrl, CRH＋/＋ stress, CRH-/- ctrl and CRH-/- stress. All mice in stress groups were under 2 h running. After 1 h, blood plasma in all groups was collected and the ex- pression of corticosterone and IL- 17A was detected by ELISA. Meanwhile, unicell suspensions of peripheral lymph node and spleen in each group were prepared too and stained by PE-CD4 and FITC-CD25, then the changes of Treg （CD4＋CD25＋） in different groups were checked by flow cytometry; all data were statistically analyzed by the software of WinMDI 2.9, SPSS 11.5, Origin 7.5 and Matlab 2-D and 3-D plot function. Results： The levels of corticosterone were signifi- cantly higher in stress groups than that in correspond- ing control groups （P〈0.05）, especially in CRH＋/＋ stress group （P〈0.01）. However, the changes of Tregs were not obvious between stress groups and control groups with respective genotypes （P〈0.05）. Compared with that in CRH＋/＋ control group, the ratio of Treg and the expres- sion of IL-17A in CRH-/- stress group were significantly higher than those in control group （P〈0.05）. Combined with the expression levels of corticosterone, Treg and Thl7, our study suggests that endogenous glucocorti- cold with basal level may cause the changes in Treg- Thl7 balance. Moreover, as the corticosterone level increases, the expression of Treg and Thl7 appears to manifest antagonistic fluctuant status with a rising ten- dency in general. Conclusion： Endogenous glucocorticoid under early stage of stress may increase the function of T lymphocyte immunity to some extent.展开更多
Corticotropin-releasing hormone is a critical component of the hypothalamic–pituitary–adrenal axis,which plays a major role in the body’s immune response to stress.Mast cells are both sensors and effectors in the i...Corticotropin-releasing hormone is a critical component of the hypothalamic–pituitary–adrenal axis,which plays a major role in the body’s immune response to stress.Mast cells are both sensors and effectors in the interaction between the nervous and immune systems.As first responders to stress,mast cells can initiate,amplify and prolong neuroimmune responses upon activation.Corticotropin-releasing hormone plays a pivotal role in triggering stress responses and related diseases by acting on its receptors in mast cells.Corticotropin-releasing hormone can stimulate mast cell activation,influence the activation of immune cells by peripheral nerves and modulate neuroimmune interactions.The latest evidence shows that the release of corticotropin-releasing hormone induces the degranulation of mast cells under stress conditions,leading to disruption of the bloodbrain barrier,which plays an important role in neurological diseases,such as Alzheimer’s disease,Parkinson’s disease,multiple sclerosis,autism spectrum disorder and amyotrophic lateral sclerosis.Recent studies suggest that stress increases intestinal permeability and disrupts the blood-brain barrier through corticotropin-releasing hormone-mediated activation of mast cells,providing new insight into the complex interplay between the brain and gastrointestinal tract.The neuroimmune target of mast cells is the site at which the corticotropin-releasing hormone directly participates in the inflammatory responses of nerve terminals.In this review,we focus on the neuroimmune connections between corticotropin-releasing hormone and mast cells,with the aim of providing novel potential therapeutic targets for inflammatory,autoimmune and nervous system diseases.展开更多
AIM To measure exogenous corticotropin-releasing factor(CRF)-induced motility of the isolated rat colon and to demonstrate the effect of pharmacologic inhibition on CRF-induced motility. METHODS The isolated vascularl...AIM To measure exogenous corticotropin-releasing factor(CRF)-induced motility of the isolated rat colon and to demonstrate the effect of pharmacologic inhibition on CRF-induced motility. METHODS The isolated vascularly-perfused rat colon was used. Luminal pressure was monitored via microtip catheter pressure transducers in the proximal and distal colon. At first, exogenous CRF was administered in a stepwise manner and the concentration of CRF yielding maximal colonic motility was selected. After recording basal colonic motility, hexamethonium, phentolamine, propranolol, atropine and tetrodotoxin were infused into the isolated colon. Initially, only the test drug was infused; then, CRF was added. The motility index was expressed as percentage change over basal level. RESULTS Administration of 1.4, 14.4, 144 and 288 pmol/L CRF progressively increased colonic motility in the proximal and distal colon. Infusion of atropine or tetrodotoxin reduced CRF-induced motility of both the proximal and distal colon, whereas hexamethonium, phentolamine and propranolol had no effect.CONCLUSION CRF-induced colonic motility appears to be mediated by local cholinergic signaling via muscarinic receptors. Muscarinic receptors are potential targets for counteracting CRF-induced colonic hypermotility.展开更多
EAE （experimental autoimmune encephalomyelitis） is an established, inducible animal model employed in the study of MS （multiple sclerosis） characterized by inflammation, BBB （blood brain barrier） malfunction, de...EAE （experimental autoimmune encephalomyelitis） is an established, inducible animal model employed in the study of MS （multiple sclerosis） characterized by inflammation, BBB （blood brain barrier） malfunction, demyelination and neuronal disruption. CRF （corticotropin releasing factor） is a neuropeptide critically associated with immune function, BBB permeability, and the hypothalamic-pituitary-adrenal axis. Potential CRF targets in the brain include astrocytes, as well as endothelial cells of cerebral microvessels, since they have been reported to express CRFR （CRF receptors）. Further, both of these cell types function critically in regulating BBB permeability. CRF-BP （CRF binding protein） is also expressed in both neurons and glial cells. Changes in the cortical CRF system could be a contributing factor to the BBB disruption associated with MS/EAE and has been suggested to play a protective role against cytokine-induced inflammation. The current study assessed alterations associated with the C57BL/6 mouse model of EAE in the cortical CRF system and correlated these events with changes to the microvascular unit. Immunohistochemical confocal microscopy was used to analyze the distribution of CRF, CRF-BP, and CRFR in the mouse cerebral cortex. The authors observed a reduction in detectable CRF immunofluorescence in the EAE motor cortex, an increase in CRFBP immunoreactivity in EAE astrocytes and a concurrent reduction in astrocytic CRFR immunofluorescence. Staining techniques were used to visualize astrocytes/microvessels to document alterations in BBB integrity. Changes in the CRF system were associated with a modification of the blood brain barrier as manifested by a poorly defined astrocytic barrier in EAE microvessels. Evidence suggests that manipulation of CRF signaling pathways offers an intriguing target for interventional therapies designed to modify BBB permeability that may be beneficial for treating disease states such as MS.展开更多
Objective: To study the inhibition effects of estrogen on the production of corticotropin-releasing hormone in human placental cells. Methods: Primary cultured placental cells were treated by ICI182, 780, a complete E...Objective: To study the inhibition effects of estrogen on the production of corticotropin-releasing hormone in human placental cells. Methods: Primary cultured placental cells were treated by ICI182, 780, a complete ER antagonist , and Tamoxifen, an ERa-mixed agonist/antagonist and ERβ antagonist for 24 h. The supernatant was havested for the radioimmunoassay of CRH. Results: 17β-estradiol inhibited the secretion of corticotropin-releasing hormone in human placental (P<0.05). ICI182, 780 stimulated the secretion of corticotropin-releasing hormone in human placental (P<0.05). Conclusion: Estrogen represses the synthesis and secretion of corticotropin-releasing hormone in human placental, which is possibly mediated by ERa.展开更多
基金Supported by Open Fund of Key Laboratory of Acupuncture Combined with Medication (Nanjing University of TCM), Ministry of Education, No. KJA200809Shanghai Rising-Star Program, No. 08QA14064Shanghai Leading Academic Discipline Project, No. S30304
文摘AIM： To investigate the effect and mechanism of electro-acupuncture lEA） at ST25 and ST37 on irritable bowel syndrome （IBS） of rats. METHODS： A total of 21 male Sprague-Dawley rats were randomly divided into normal group, model group and EA group. A rat model of IBS was established by constraining the limbs and distending the colorectum of rats. Rats in EA group received bilateral EA at ST25 and ST37 with a sparse and intense waveform at a frequency of 2/50 Hz for 15 min, once a day for 7 d as a course. Rats in normal and model groups were stimulated by distending colorectum （CR）. An abdominal withdrawal reflex （AWR） scoring system was used to evaluate improvements in visceral hypersensitivity. Toluidine blue-improved method, immunohistochemistry and radioimmunoassay were used to observe mucosal mast cells （MC）, changes of substance P （SP） and substance P receptor （SPR） in colon and change of corticotropin-releasing hormone （CRH） in hypothalamus. RESULTS： The threshold of visceral sense was significantly lower in model group than in normal group,and significantly higher in EA group than in model group. The number of mucosal MC was greater in model group than in normal group and significantly smaller in EA group than in model group. The CRH level in hypothalamus of rats was significantly higher in model group than in normal group, which was remarkably decreased after electro-acupuncture treatment. The SP and SPR expression in colon of rats in model group was decreased after electro-acupuncture treatment. CONCLUSION： EA at ST25 and ST37 can decrease the number of mucosal MC and down-regulate the expression of CRH in hypothalamus, and the expression of SP and SPR in colon of rats with IBS.
文摘Disordered signalling between the brain and the gut are generally accepted to underlie the functional bowel disorder, irritable bowel syndrome(IBS). However, partly due to the lack of disease-defining biomarkers, understanding the aetiology of this complex and multifactorial disease remains elusive. This common gastrointestinal disorder is characterised by alterations in bowel habit such as diarrhoea and/or constipation, bloating and abdominal pain, and symptom exacerbation has been linked with periods of stress, both psychosocial and infection-related. Indeed, a high level of comorbidity exists between IBS and stress-related mood disorders such as anxiety and depression. Moreover, studies have observed alterations in autonomic output and neuro-endocrine signalling in IBS patients. Accumulating evidence indicates that a maladaptive stress response, probably mediated by the stress hormone, corticotropin-releasing factor contributes to the initiation, persistence and severity of symptom flares.Other risk factors for developing IBS include a positive family history, childhood trauma, dietary factors and prior gastrointestinal infection. An emerging role has been attributed to the importance of immune factors in the pathophysiology of IBS with evidence of altered cytokine profiles and increased levels of mucosal immune cells. These factors have also been shown to have direct effects on neural signalling. This review discusses how pathological changes in neural, immune and endocrine pathways, and communication between these systems, contribute to symptom flares in IBS.
基金Supported by China Postdoctoral Science Foundation funded project,No.200801260,No.20080430117the National Basic Research Program of China 973 program,No.2009CB522900the Specialized Research Fund for the Doctoral Program of Higher Education No.20123107110008
文摘AIM: To investigate the effect of electroacupuncture on corticotropin-releasing hormone(CRH) in the colon, spinal cord, and hypothalamus of rats with chronic visceral hypersensitivity.METHODS: A rat model of chronic visceral hypersensitivity was generated according to the internationally accepted method of colorectal balloon dilatation. In the 7th week after the procedure, rats were randomly divided into a model group(MG), electroacupuncture group(EA), and sham electroacupuncture group(S-EA). After treatment, the abdominal withdrawal reflex(AWR) score was used to assess the behavioral response of visceral hyperalgesia. Immunohistochemistry(En Vision method), ELISA, and fluorescence quantitative PCR methods were applied to detect the expression of CRH protein and m RNA in the colon, spinal cord, and hypothalamus.RESULTS: The sensitivity of the rats to the colorectal distension stimulus applied at different strengths(20-80 mm Hg) increased with increasing stimulus strength, resulting in increasing AWR scores in each group. Compared with NG, the AWR score of MG was significantly increased(P < 0.01). After conducting EA, the AWR scores of the rats were decreased compared with MG rats. The relative expression of CRH m RNA in the colon, spinal cord, and hypothalamus of MG rats was significantly increased compared with NG rats(P < 0.01). CRH m RNA in the colon and spinal cord of EA and S-EA rats was decreased to varying degrees(P > 0.05) compared with normal rats(NG). However, the decrease in EA compared with MG rats was statistically significant(P < 0.01). The average optical density of CRH expression in the colon of the MG rats was significantly enhanced compared with NG(P < 0.05), while the average optical density of CRH expression in the EA and S-EA rats was significantly decreased compared with MG rats(P < 0.01, P < 0.05, respectively). Compared with MG rats, the CRH concentration in the spinal cord of EA rats was significantly reduced(P < 0.01), but there was no significant change in S-EA rats(P > 0.05).CONCLUSION
基金Supported by National Natural Science Foundation of China,No.81473506Natural Science Foundation of Zhejiang Province,No.LY13H030011 and No.LY17H290009+2 种基金State Administration of Traditional Chinese Medicine of Zhejiang Province,No.2013ZB050Department of Zhejiang Province to Build Funded Project,No.WKJ-ZJ-1531Zhejiang TCM Science and Technology Project,No.2016ZB047,No.2017ZA056 and No.2018ZB046
文摘AIM To explore the significance of corticotropin-releasing hormone(CRH)-receptor(R)2 in mucosal healing of dextran sulfate sodium(DSS)-induced colitis and the effect of Tong-Xie-Yao-Fang(TXYF) on CRH-R2 expression and regulation.METHODS Ulcerative colitis was induced in mice by administration of 3%(w/v) DSS for 7 d. Once the model was established,mice were administered urocortin-2(30 μg/kg), a peptide which binds exclusively to CRH-R2, or various doses of aqueous TXYF extracts(2.8-11.2 g/kg), a CRH-R2 antagonist Astressin(Ast)2B(20 μg/kg), Ast2B + Ucn2, or Ast2B with various doses of aqueous TXYF extracts for 9 d. Colonic mucosal permeability was then evaluated by measuring the fluorescence intensity in serum. The colitis disease activity index(DAI), histology, body weight loss and colon length were assessed to evaluate the condition of colitis. Terminal deoxynucleotidyl transferase d UTP nick-end labeling was used to detect apoptosis of the intestinal epithelial cells. The expression level of Ki-67 represented the proliferation of colonic epithelial cells and was detected by immunohistochemistry. The expression levels of inflammation cytokines IL-6, TNF-α and CXCL-1 were examined in colon tissues using real-time PCR and ELISA kits.RESULTS Compared with the DSS group, mice treated with the CRH-R2 antagonist Ast2B showed greater loss of body weight, shorter colon lengths(4.90 ± 0.32 vs 6.21 ± 0.34 cm, P < 0.05), and higher DAI(3.61 ± 0.53 vs 2.42 ± 0.32, P < 0.05) and histological scores(11.50 ± 1.05 vs 8.33 ± 1.03, P < 0.05). Additionally, the Ast2B group showed increased intestinal permeability(2.76 ± 0.11 μg/mL vs 1.47 ± 0.11 μg/mL, P < 0.001), improved secretion of inflammatory cytokines in colon tissue, and reduced colonic epithelial cell proliferation(4.97 ± 4.25 vs 22.51 ± 8.22, P < 0.05). Increased apoptosis(1422.39 ± 90.71 vs 983.01 ± 98.17, P < 0.001) was also demonstrated. The Ucn2 group demonstrated lower DAI(0.87 ± 0.55 vs 2.42 ± 0.32, P < 0.001) and histological scores(4.33 ± 1.50
基金This work was supported by the Special Funds for Major State Basic Research Projects （2005CB522600）, the Eleventh Five-Year Science and Technology Project of PLA （06G080）, and Natural Science Foundation Project of CQCSTC （2009BB5316）
文摘In trauma, infection and hemorrhagic shock derived stress, primary and secondary injury may result in severe derangement in the internal environment. The abnormal changes of immune-mediated inflammation interfere its pathogenesis and development directly. In recent years, various aspects of neuroendocrine responses, especially the regulatory effects of hypothalamic-pituitary-adrenal and sympathetico-adrenomedullary axes in inflammatory diseases have been the focus of research. Most importantly,corticotropin-releasing hormone （CRH） acts as a key player in the regulation of interactions between neuroendocrine and immunity both directly and indirectly. The paper summarized the recent development of CRH in the immune-mediated inflammation.
基金Supported by Grants-in-Aid for Scientific Research(C)from the Ministry of Education,Culture,Sports,Science,and Tech-nology of Japanthe Foundation for the Promotion of Can-cer Research and Mitsui Life Social Welfare Foundation
文摘AIM: To examine whether commensal bacteria are a contributing cause of stress-related mucosal inflammation.
基金National Natural Science Foundation of China(No.81073073,No.81403153)
文摘Objective To investigate the mechanisms through which kidney-tonifying herbs（KTHs） and liver-clearing herbs（LCHs） in Dingjing Decoction（DJD） regulate premature ovarian failure（POF）. Methods One hundred and fifty Sprague-Dawley rats were randomly divided into five groups such as control, model, KTHs, LCHs, and DJD groups. POF-related biological molecules were examined. Factor analysis was performed to investigate the regulatory networks and key biomolecules involved in mediating POF after treatment with KTHs and LCHs. Results The master regulatory factors in the reproductive endocrine network associated with KTHs intervention included four molecules in the pituitary-ovarian axis, cortisol（CORT） in the target gland of pituitary-adrenal axis, and some molecules in the hypothalamus. In contrast, the master regulatory factors associated with LCHs intervention included four molecules in the pituitary-ovarian axis and some molecules in the hypothalamus; No biomolecules in the pituitary-adrenal axis were involved in the LCH-mediated mechanisms.Gonadotropin-releasing hormone（Gn RH）, which was identified as a common biological molecule in the hypothalamus, was involved in regulating the reproductive endocrine network in association with KTHs intervention. Conclusion KTHs directly regulates biological molecules in the pituitary-adrenal axis and indirectly regulates those in the pituitary-adrenal axis through the hypothalamus, while the LCHs only exert its effects indirectly. Gn RH is the key biological molecule associated with KTHs intervention.
基金Supported by Natural Science Foundation-funded Project:Mechanism of Electroacupuncture Regulating CRF-NLRP6 InflammasomeRelated Pathways in Intestinal Flora Immune Dialogue (No. 81804193)Leading Talents of Jiangsu Provincial Administration of TCM-funded Project:Clinical Effect and Mechanism of Acupuncture and Moxibustion on Irritable Bowel Syndrome (No. SLJ0206)+1 种基金Peak Talent of Jiangsu Province Hospital of Chinese Medicine-funded Project:Clinical Effect and Mechanism of Acupuncture and Moxibustion in the Treatment of Functional Gastrointestinal Diseases (No. y2018rc05)Research and Innovation Project for Postgraduates of Jiangsu Province-funded Project:Mechanism of Electroacupuncture Regulating Bile Acid Receptor to Alleviate Visceral Hypersensitivity in Irritable Bowel Syndrome (No. YCX20_1469)。
文摘OBJECTIVE: To investigate whether electroacupuncture(EA) at bilateral Tianshu(ST25) and Zusanli(ST36) acupoints could alleviate stress-induced irritable bowel syndrome(IBS) and evaluate its effect on gut microbiota and corticotropin-releasing factor(CRF). METHODS: Thirty C57BL/6 mice were randomly divided into the normal, water avoidance stress(WAS), and WAS+EA groups(10 mice per group). An experimental model of IBS was established by exposing the animals to WAS. The mice were treated with EA at the bilateral Tianshu(ST25) and Zusanli(ST36) acupoints. The abdominal withdrawal reflex test was conducted to evaluate visceral sensitivity in IBS. Gut microbiota was analyzed using 16S r RNA sequencing and analysis. The expression of CRF was determined using immuneofluorescence and quantitative real-time polymerase chain reaction. RESULTS: EA alleviated visceral hypersensitivity in a mouse model of WAS-induced IBS. It modulated the dysbiosis of gut microbiota induced by WAS. Moreover, it suppressed the WAS-induced overexpression of CRF in colon tissues. CONCLUSION: The findings of this study suggest that EA alleviated WAS-induced IBS via mechanisms possibly involving the modulation of the dysbiosis of gut microbiota and suppression of CRF expression.
文摘Objective Corticotropin-releasing hormone（CRH）plays an important role in neuroendocrine,autonomic and behavioral responses to stressors.In the present study,the effect of chronic unpredictable mild stress（CUMS）on CRH neurons was investigated in rat brain.Methods The rats were exposed to one of the stressors each day for 21 d.Immunostaining was performed to detect the CRH-positive neurons in the paraventricular nucleus（PVN）of the hypothalamus and in amygdala.Results After the stress protocol,the animals showed a reduction in body weight gain as well as reduced sucrose preference and locomotor activity.Interestingly,the CRH neurons in both PVN and central nucleus of the amygdala（CeA）were stimulated by CUMS.The densities of CRH-containing neurons in both PVN and CeA were significantly higher than those in control group.Conclusion The CRH systems in PVN and CeA may both contribute to depression-like behaviors during CUMS.
基金Supported by The National Institute of Diabetes and Digestive and Kidney Diseases R01 grant DK-57238Center Grant DK-41301 (Clinical core)+1 种基金Veteran Administration Research Career Scientist Award (YT)NIH DK-78676 (MM)
文摘AIM: To assess corticotropin-releasing factor receptor 2 (CRF 2 ) expression in the colon of healthy subjects and patients with ulcerative colitis (UC). METHODS: We examined CRF2 gene and protein expression in the distal/sigmoid colonic mucosal biopsies from healthy subjects and patients with UC (active or disease in remission), human immunodeficiency virus (HIV) and functional bowel disease (FBD) by reverse transcriptionpolymerase chain reaction and immunofluorescence. RESULTS: Gene expression of CRF2 was demonstrated in the normal human colonic biopsies, but not in the human colorectal adenocarcinoma cell line Caco2. Receptor protein localization showed immunoreactive CRF 2 receptors in the lamina propria and in the epithelial cells of the distal/sigmoid biopsy samples. Interestingly, CRF 2 immunoreactivity was no longer observed in epithelial cells of patients with mild-moderately active UC and disease in remission, while receptor protein expression did not change in the lamina propria. No differences in CRF 2 expression profile were observed in distal/sigmoid intestinal biopsies from HIV infection and FBD patients, showing no signs of inflammation. CONCLUSION: The down-regulation of the CRF2 receptor in the distal/sigmoid biopsies of UC patients is indicative of change in CRF 2 signalling associated with the process of inflammation.
文摘The activities of corticotropin-releasing factor(CRF) and related peptides are mediated a number of receptors with seven transmembrane domains that are coupled to the Gs and Gq proteins. These receptors are known as CRF-Rs. In vitro studies have evidenced that urocortin(UCN) and CRF provoke an increase in the contractility of the uterus which is induced by endometrial prostaglandin F2 a. Furthermore, through trophoblasts, it stimulates the secretion of adrenocorticotropic hormone(ACTH) and prostaglandin PGE2 and has a vasodilatory effect on the placenta. While it is well known that the placenta produces considerable quantities of CRF, several studies have, however, excluded that the placenta can generate significant quantities of UCN. In the short term, the human fetal adrenal gland produces more cortisol and dehydroepiandrosterone sulfate. The gestational tissues express UCN3 and UCN2 m RNA in cytotrophoblast and syncytiotrophoblast cells, while UCN2 is only to be found in the maternal and fetal vessels and amniotic cells. Nevertheless, gestational tissues express UCN2 and UCN3 differentially and do not stimulate placental ACTH secretion. In term pregnancies, maternal plasma levels of CRF and UCN are lower than at the beginning of pregnancy and are correlated to labor onset. Conversely,they do not decrease in post-term pregnancies. This evidence would seem to indicate that the fine-regulated expression of these neuropeptides is important in determining the duration of human gestation. In this scenario, low concentrations of UCN in the amniotic fluid at mid-term may be considered a sign of predisposition to preterm birth.
文摘Objective： To observe the effect of moxibustion on the protein and mRNA expressions of corticotropin-releasing factor （CRF） and corticotropin-releasing factor receptor 2 （CRFR1） in hypothalamus of trinitrobenzene sulfonic acid （TNBS）-induced experimental colitis rats, and to explore the central mechanisms of moxibustion in improving visceral pain and the pain-related emotions in experimental colitis rats. Methods： Thirty-six Sprague-Dawley （SD） rats were randomly divided into a normal group （NG）, a model group （MG）, a herb-partitioned moxibustion group （HPMG） and a sham herb-partitioned moxibustion group （SHPMG）. Except the NG, rats in the remaining three groups all received TNBS enema to establish experimental colitis models. The HPMG received herb-partitioned moxibustion （HPM） at bilateral Tianshu （ST 25） and Qihai （CV 6） for intervention; for the SHPMG, the herbal cakes and moxa cones were only placed on the acupoints but not ignited; rats in the MG and NG were only fixed in the same way as those in the HPMG but did not receive any treatment. At the end of the intervention, the abdominal withdrawal reflex （AWR） score, the open field test （OFT） score and the elevated plus maze （EPM） score were observed to measure the changes in visceral pain and pain-related emotions of the rats. The enzyme-linked immunosorbent assay （ELISA） was used to examine the expressions of CRF and CRFR1 proteins in hypothalamus; the fluorescence-based quantitative polymerase chain reaction （PCR） was used to detect the expressions of CRF and CRFR1 mRNAs in hypothalamus. Results： Compared with the NG, the AWR score increased significantly and the OFT and EPM scores dropped significantly in the MG （all P〈0.05）, and the expressions of hypothalamic CRF and CRFR1 proteins and mRNAs increased significantly （all P〈0.01）. Compared with the MG and SHPMG, the AWR score dropped significantly and the OFT and EPM scores increased significantly in the HPMG （all P〈0.01
基金National Natural Science Foundation of China，Natural Science Foundation Project of CQ CSTC，Foundation for Returned Scholars Sponsored by Department of Human Resources and Social Security of China
文摘Objective： To explore the changes of Treg-Thl 7 balance influenced by corticosterone, major ef- fect hormone ofhypothalamic-pituitary-adrenal （HPA） axis under running stress. Methods： Atotal of 25 corticotropin-releasing hor- mone （CRH） wildtype （CRH＋/＋） and knockout （CRH-/-） mice were adopt and divided into 4 groups as follows： CRH＋/＋ ctrl, CRH＋/＋ stress, CRH-/- ctrl and CRH-/- stress. All mice in stress groups were under 2 h running. After 1 h, blood plasma in all groups was collected and the ex- pression of corticosterone and IL- 17A was detected by ELISA. Meanwhile, unicell suspensions of peripheral lymph node and spleen in each group were prepared too and stained by PE-CD4 and FITC-CD25, then the changes of Treg （CD4＋CD25＋） in different groups were checked by flow cytometry; all data were statistically analyzed by the software of WinMDI 2.9, SPSS 11.5, Origin 7.5 and Matlab 2-D and 3-D plot function. Results： The levels of corticosterone were signifi- cantly higher in stress groups than that in correspond- ing control groups （P〈0.05）, especially in CRH＋/＋ stress group （P〈0.01）. However, the changes of Tregs were not obvious between stress groups and control groups with respective genotypes （P〈0.05）. Compared with that in CRH＋/＋ control group, the ratio of Treg and the expres- sion of IL-17A in CRH-/- stress group were significantly higher than those in control group （P〈0.05）. Combined with the expression levels of corticosterone, Treg and Thl7, our study suggests that endogenous glucocorti- cold with basal level may cause the changes in Treg- Thl7 balance. Moreover, as the corticosterone level increases, the expression of Treg and Thl7 appears to manifest antagonistic fluctuant status with a rising ten- dency in general. Conclusion： Endogenous glucocorticoid under early stage of stress may increase the function of T lymphocyte immunity to some extent.
基金supported by the National Natural Science Foundation of China,Nos.81671387(to YNQ),81701375(to HQD)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),China.
文摘Corticotropin-releasing hormone is a critical component of the hypothalamic–pituitary–adrenal axis,which plays a major role in the body’s immune response to stress.Mast cells are both sensors and effectors in the interaction between the nervous and immune systems.As first responders to stress,mast cells can initiate,amplify and prolong neuroimmune responses upon activation.Corticotropin-releasing hormone plays a pivotal role in triggering stress responses and related diseases by acting on its receptors in mast cells.Corticotropin-releasing hormone can stimulate mast cell activation,influence the activation of immune cells by peripheral nerves and modulate neuroimmune interactions.The latest evidence shows that the release of corticotropin-releasing hormone induces the degranulation of mast cells under stress conditions,leading to disruption of the bloodbrain barrier,which plays an important role in neurological diseases,such as Alzheimer’s disease,Parkinson’s disease,multiple sclerosis,autism spectrum disorder and amyotrophic lateral sclerosis.Recent studies suggest that stress increases intestinal permeability and disrupts the blood-brain barrier through corticotropin-releasing hormone-mediated activation of mast cells,providing new insight into the complex interplay between the brain and gastrointestinal tract.The neuroimmune target of mast cells is the site at which the corticotropin-releasing hormone directly participates in the inflammatory responses of nerve terminals.In this review,we focus on the neuroimmune connections between corticotropin-releasing hormone and mast cells,with the aim of providing novel potential therapeutic targets for inflammatory,autoimmune and nervous system diseases.
文摘AIM To measure exogenous corticotropin-releasing factor(CRF)-induced motility of the isolated rat colon and to demonstrate the effect of pharmacologic inhibition on CRF-induced motility. METHODS The isolated vascularly-perfused rat colon was used. Luminal pressure was monitored via microtip catheter pressure transducers in the proximal and distal colon. At first, exogenous CRF was administered in a stepwise manner and the concentration of CRF yielding maximal colonic motility was selected. After recording basal colonic motility, hexamethonium, phentolamine, propranolol, atropine and tetrodotoxin were infused into the isolated colon. Initially, only the test drug was infused; then, CRF was added. The motility index was expressed as percentage change over basal level. RESULTS Administration of 1.4, 14.4, 144 and 288 pmol/L CRF progressively increased colonic motility in the proximal and distal colon. Infusion of atropine or tetrodotoxin reduced CRF-induced motility of both the proximal and distal colon, whereas hexamethonium, phentolamine and propranolol had no effect.CONCLUSION CRF-induced colonic motility appears to be mediated by local cholinergic signaling via muscarinic receptors. Muscarinic receptors are potential targets for counteracting CRF-induced colonic hypermotility.
文摘EAE （experimental autoimmune encephalomyelitis） is an established, inducible animal model employed in the study of MS （multiple sclerosis） characterized by inflammation, BBB （blood brain barrier） malfunction, demyelination and neuronal disruption. CRF （corticotropin releasing factor） is a neuropeptide critically associated with immune function, BBB permeability, and the hypothalamic-pituitary-adrenal axis. Potential CRF targets in the brain include astrocytes, as well as endothelial cells of cerebral microvessels, since they have been reported to express CRFR （CRF receptors）. Further, both of these cell types function critically in regulating BBB permeability. CRF-BP （CRF binding protein） is also expressed in both neurons and glial cells. Changes in the cortical CRF system could be a contributing factor to the BBB disruption associated with MS/EAE and has been suggested to play a protective role against cytokine-induced inflammation. The current study assessed alterations associated with the C57BL/6 mouse model of EAE in the cortical CRF system and correlated these events with changes to the microvascular unit. Immunohistochemical confocal microscopy was used to analyze the distribution of CRF, CRF-BP, and CRFR in the mouse cerebral cortex. The authors observed a reduction in detectable CRF immunofluorescence in the EAE motor cortex, an increase in CRFBP immunoreactivity in EAE astrocytes and a concurrent reduction in astrocytic CRFR immunofluorescence. Staining techniques were used to visualize astrocytes/microvessels to document alterations in BBB integrity. Changes in the CRF system were associated with a modification of the blood brain barrier as manifested by a poorly defined astrocytic barrier in EAE microvessels. Evidence suggests that manipulation of CRF signaling pathways offers an intriguing target for interventional therapies designed to modify BBB permeability that may be beneficial for treating disease states such as MS.
基金Supported by National Natural Science Foundation of China(No.39870300)
文摘Objective: To study the inhibition effects of estrogen on the production of corticotropin-releasing hormone in human placental cells. Methods: Primary cultured placental cells were treated by ICI182, 780, a complete ER antagonist , and Tamoxifen, an ERa-mixed agonist/antagonist and ERβ antagonist for 24 h. The supernatant was havested for the radioimmunoassay of CRH. Results: 17β-estradiol inhibited the secretion of corticotropin-releasing hormone in human placental (P<0.05). ICI182, 780 stimulated the secretion of corticotropin-releasing hormone in human placental (P<0.05). Conclusion: Estrogen represses the synthesis and secretion of corticotropin-releasing hormone in human placental, which is possibly mediated by ERa.
