Sex, pain, alcoholism and anxiety symptoms are predictive for systemic cortisol levels in oral cancer patients / Sexo, dor, etilismo e sintomas de ansiedade são preditivos para níveis sistêmicos de cortisol em paciente com câncer de boca

Pacientes com câncer podem apresentar uma desregulação do eixo hipotálamohipófise-adrenal (HPA) e secreção aumentada do hormônio cortisol. Níveis elevados de cortisol têm sido associados a pior prognóstico de diferentes tipos de câncer. Embora alterações psicológicas como ansiedade e depressão possam deflagrar uma secreção anormal de cortisol, pouco se sabe sobre a influência destas desordens emocionais na desregulação do eixo HPA em pacientes com câncer quando avaliadas em conjunto com variáveis demográficas, clinicopatológicas e biocomportamentais. Este estudo transversal avaliou os níveis plasmáticos de cortisol em 133 pacientes com carcinoma espinocelular (CEC) de boca e sua associação com variáveis demográficas, clínicopatológicas, biocomportamentais e psicológicas. Os níveis plasmáticos de cortisol foram mensurados por eletroquimioluminescência, e os níveis de ansiedade e depressão foram avaliados pelo Inventário de Ansiedade (BAI) e de Depressão (BDI) de Beck, respectivamente. Os dados demográficos, clinicopatológicos e biocomportamentais foram coletados dos prontuários dos pacientes. Os resultados da análise multivariada mostraram que homens com CEC de boca apresentaram 4,5 vezes mais chances de terem níveis elevados de cortisol plasmático do que as mulheres com a doença (OR=4,472; p=0,018). A presença de dor relacionada ao tumor primário também foi preditivo para maiores níveis de cortisol (OR=5,388; p=0,003). A ausência de histórico de consumo crônico de álcool foi um fator protetor para concentrações muito elevadas do hormônio nos pacientes com CEC de boca (OR=0,104; p= 0,004). Sintomas de ansiedade mensurados pelo BAI como "mãos trêmulas" (OR=0,192; p= 0,016) e estar "nervoso" (OR=0,207; p= 0,0004) foram associados a menores níveis de cortisol. Por outro lado, o sentimento de "medo de perder o controle" foi um fator de risco para níveis muito elevados de cortisol plasmático (OR=6,508; p= 0,0004). O score global e os sintomas específicos de depressão mensurados pelo BDI não foram preditivos para os níveis plasmáticos hormonais (p< 0,05). Juntos, os resultados mostram que sexo, dor, consumo de álcool e sintomas de ansiedade são variáveis independentes para os níveis sistêmicos de cortisol nos pacientes com câncer de boca. Portanto, intervenção psicológica, bem como o controle da dor e do alcoolismo devem ser considerados para a prevenção dos efeitos negativos da desregulação da secreção de cortisol nos pacientes diagnosticados com câncer de boca(AU)

Cancer patients may have a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and abnormal secretion of cortisol. Increased cortisol levels have been associated with worse prognosis in different types of cancer. Although anxiety and depression can trigger an abnormal cortisol secretion, little is known regarding the influence of these emotional disorders on HPA axis dysregulation in cancer patients when evaluating together with demographic, clinicopathological and biobehavioral variables. This crosssectional study analyzed the plasma cortisol levels of 133 patients with oral squamous cell carcinoma (OSCC) and its association with demographic, clinicopathological, biobehavioral and psychological variables. Plasma cortisol levels were measured by electrochemiluminescence, and anxiety and depression symptoms were assessed using Beck Anxiety Inventory (BAI) and Depression (BDI), respectively. Demographic, clinicopathological and biobehavioral data were collected from patients' medicalrecords. Results from multivariate analysis showed that men with OSCC were 4.5 times more likely to have higher plasma cortisol levels than women (OR = 4.472, p = 0.018). The presence of cancer-induced pain was predictive for higher cortisol levels (OR = 5.388, p = 0.003). The absence of chronic alcohol consumption history was a protective factor for highest hormonal concentrations in oral cancer patients (OR = 0.104, p = 0.004). Anxiety symptoms measured by BAI as "hands trembling" (OR = 0.192, p = 0.016) and being "nervous" (OR = 0.207, p = 0.0004) were associated with lower cortisol levels. In contrast, the feeling of "fear of losing control" was a risk factor for highest systemic levels cortisol (OR = 6.508, p = 0.0004). The global score and specific symptoms of depression measured by the BDI were not predictive for plasma hormone levels (p < 0.05). Together, our results show that sex, pain, alcohol consumption and anxiety symptoms are independent variables for systemic cortisol levels in patients with oral cancer. Therefore, psychological intervention, as well as control of pain and alcohol consumption, should be considered to prevent the negative effects of cortisol secretion dysregulation in patients with oral câncer(AU)

Research progress of the role of microRNAs in puberty initiation / 中国学校卫生

Abstract@#MiRNAs are a type of single-stranded, endogenous, non-coding small RNAs, which can regulate the post-transcriptional expression of genes and a variety of biological functions. Puberty development involves a complex regulatory network, among which the the hypothalamic-pituitary-gonad axis may play the key role. Studies have found that there was a relationship between the miRNAs and puberty development. The absence and abnormal expression of miRNAs can affect the initiation of puberty. But the mechanism is not clear. It may be related to the secretion of GnRH in the hypothalamus. This article mainly introduced several miRNAs which were currently closely related to the initiation of puberty, and reviewed their role and possible mechanisms in the initiation of puberty.

Acute Physical Stress Preconditions the Heart Against Ischemia/Reperfusion Injury Through Activation of Sympathetic Nervous System / Estresse Físico Agudo Precondiciona o Coração Contra a Injúria por Isquemia/Reperfusão Através da Ativação do Sistema Nervoso Simpático

Abstract Background: Stress is defined as a complicated state that related to homeostasis disturbances, over-activity of the sympathetic nervous system and hypothalamus-pituitary-adrenal axis responses. Cardiac preconditioning reduces myocardial damages. Objective: This study was designed to assess the cardioprotective effects of acute physical stress against ischemia/reperfusion (I/R) injury through the activation of the sympathetic nervous system. Methods: Thirty-two male Wistar rats were divided into four groups; (1) IR (n = 8): rats underwent I/R, (2) Acute stress (St+IR) (n = 8): physical stress induced 1-hour before I/R, (3) Sympathectomy (Symp+IR) (n = 8): chemical sympathectomy was done 24-hours before I/R and (4) Sympathectomy- physical stress (Symp+St+IR) (n = 8): chemical sympathectomy induced before physical stress and I/R. Chemical sympathectomy was performed using 6-hydroxydopamine (100 mg/kg, sc). Then, the hearts isolated and located in the Langendorff apparatus to induce 30 minutes ischemia followed by 120 minutes reperfusion. The coronary flows, hemodynamic parameters, infarct size, corticosterone level in serum were investigated. P < 0.05 demonstrated significance. Results: Physical stress prior to I/R could improve left ventricular developed pressure (LVDP) and rate product pressure (RPP) of the heart respectively, (63 ± 2 versus 42 ± 1.2, p < 0.05, 70 ± 2 versus 43 ± 2.6, p < 0.05) and reduces infarct size (22.16 ± 1.3 versus 32 ± 1.4, p < 0.05) when compared with the I/R alone. Chemical sympathectomy before physical stress eliminated the protective effect of physical stress on I/R-induced cardiac damages (RPP: 21 ± 6.6 versus 63 ± 2, p < 0.01) (LVDP: 38 ± 4.5 versus 43 ± 2.6, p < 0.01) (infarct size: 35 ± 3.1 versus 22.16 ± 1.3, p < 0.01). Conclusion: Findings indicate that acute physical stress can act as a preconditional stimulator and probably, the presence of sympathetic nervous system is necessary.

Resumo Fundamento: O estresse é definido como um estado complicado de distúrbios da homeostase, hiperatividade do sistema nervoso simpático e das respostas do eixo hipotálamo-hipófise-adrenal. O pré-condicionamento cardíaco diminui os danos do miocárdio. Objetivo: Esse estudo avaliou os efeitos cardioprotetores do estresse físico agudo contra a lesão por isquemia-reperfusão (I/R) através da ativação do sistema nervoso simpático. Métodos: Trinta e dois ratos machos Wistar foram divididos em quatro grupos; (1) IR (n = 8): ratos submetidos a I/R, (2) Estresse agudo (St+IR) (n = 8): estresse físico induzido 1 hora antes da I/R, (3) Simpatectomia (Symp+IR) (n = 8): a simpatectomia química foi realizada 24 horas antes da I/R e (4) Simpatectomia-estresse físico (Symp+St+IR) (n = 8): simpatectomia induzida antes do estresse físico e da I/R. A simpatectomia química foi realizada com 6-hidroxidopamina (100 mg/kg, SC). Em seguida, os corações foram isolados e colocados em aparato de Lagendorff por 30 minutos para induzir isquemia, seguida de reperfusão por 120 minutos. Os fluxos coronarianos, os parâmetros hemodinâmicos, o tamanho do infarto e os níveis de corticosterona plasmática foram investigados. Valores de p < 0,05 foram considerados significativos. Resultados: O estresse físico anterior à I/R pode melhorar a pressão desenvolvida no ventrículo esquerdo (PDVE) e duplo produto (DP), respectivamente, (63 ± 2 versus 42 ± 1,2, p < 0,05, 70 ± 2 versus 43 ± 2,6, p < 0,05) e reduzir o tamanho do infarto (22,16 ± 1,3 versus 32±1,4, p < 0,05) quando comparado com a I/R isoladamente. A simpatectomia química antes do estresse físico eliminou o efeito protetor do estresse físico sobre os danos cardíacos induzidos pela I/R (DP: 21 ± 6,6 versus 63 ± 2, p < 0,01) (PDVE: 38 ± 4,5 versus 43 ± 2,6, p < 0,01) (tamanho do infarto: 35 ± 3,1 versus 22,16 ± 1,3, p < 0,01). Conclusão: Os achados indicam que o estresse físico agudo pode funcionar como um estimulador pré-condicional e, provavelmente, a presença do sistema nervoso simpático é necessária.

Effects of endogenous glucocorticoid deprivation on immune response of allergic rhinitis in mice / 中华耳鼻咽喉头颈外科杂志

Objective@#To study the effect of dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis on the pathogenesis of allergic rhinitis (AR) by the mouse model of decreased endogenous glucocorticoid (GC) after adrenalectomy, and further explore the mechanism of neural-endocrine regulation.@*Methods@#According to literatures, adrenalectomized (ADX) mice and AR model were established. Eighty mice were randomly divided into four groups (n=20 per group) including control group, AR group of normal mice (AR group), AR group of bilateral ADX (bilateral ADX/AR group) and AR group of unilateral ADX (unilateral ADX/AR group). In order to assess the model of ADX, adrenal gland tissue was assayed by HE staining and the plasma adrenocorticotropic hormone (ACTH) and cortisol (CORT) concentrations were measured by enzyme-linked immunosorbent assay (ELISA). The behavioral observation, OVA-sIgE assessments and count of eosinophils/mast cells by the HE/Toluidine Blue staining of nasal septum mucosa tissue were performed to evaluate the AR model. The expression of peripheral blood CD4+ IL4+ T cells (Th2 cells) and CD4+ IFN-γ+ T cells (Th1 cells), splenocytes of CD4+ CD25+ Treg cells (Treg cells) were measured by flow cytometry to study the influence of endogenous GC on immunological indexes in different groups of mice. SPSS 16.0 software was used to analyze the data.@*Results@#The concentrations of OVA-sIgE in control group, AR group, bilateral ADX/AR group and unilateral ADX/AR group mice were (28.86±3.62) ng/ml, (76.27±16.47) ng/ml, (48.37±8.89) ng/ml, (49.86±7.19) ng/ml, respectively. There was statistically significant difference between control group and AR group (t=7.09, P<0.05), AR group and bilateral ADX/AR group (t=4.81, P<0.05), AR group and unilateral ADX/AR group (t=5.21, P<0.05). The level of Th2 cells in different four groups were (0.71±0.24)%, (7.03±1.95)%, (2.44±2.06)%, (3.20±1.21)%, respectively. There was statistically significant difference between control group and AR group (t=-2.93, P<0.05), AR group and bilateral ADX/AR group (t=-4.67, P<0.05), AR group and unilateral ADX/AR group (t=-3.61, P<0.05). The expression of Th2 in bilateral ADX/AR group is lower than that in unilateral ADX/AR group without significant difference (t=4.39, P>0.05). Meanwhile, the level of Th1 cells in different four groups was (0.58±0.76)%, (0.57±0.59)%, (0.72±0.34)%, (1.03±0.32)%, respectively, with no significant difference among these groups. The proportion of Treg cells was (11.10±2.18)%, (4.10±1.07)%, (7.15±0.92)%, (4.58±1.05)%, respectively, with significant difference between control and other groups (t value was -7.171, -8.273, -8.360, respectively, all P<0.05). Compared with AR group, Treg cells increased significantly in bilateral ADX/AR group (t=-2.607, P<0.05). In addition, lower expression of eosinophil and mast cell were detected in the local nasal tissue of bilateral ADX/AR group, and mast cell degranulation wasn′t be observed.@*Conclusion@#Unilateral or bilateral ADX leads to HPA axis dysfunction and endogenous GC deprivation, possibly regulating the mechanism of AR through Th1/Th2 immune bias and Tregs cell′ activity.

Developmental pattern of hypothalamic-pituitary-adrenal axis during pubertal transition and implications for emotional disorders / 中华预防医学杂志

During an individual's life, puberty is not only a crucial phase for physical development, but a key period for neuroendocrine transformation. As a major neuroendocrine axis, the influence of hypothalamic-pituitary-adrenal (HPA) axis's changes during puberty on mental and physical health, as well as emotional symptoms, is causing a growing attention. However, information of its developing pattern and circadian variation is limited. Recent research has demonstrated that certain developing pattern of HPA axis in puberty is closely related to the adolescent emotional disorders, which highlights the recognition of HPA functions developing paths under both resting and stress state and the evaluation of its prediction effect for the adolescent emotional disorders. Generally, cortisol awakening response is utilised to assess HPA functions. Elaborating the variation of HPA axis functions from the puberty to the later developing process provides much guiding significance for the early screening, intervention and treatment of adolescent emotional disorders.

Hypothalamus-Pituitary-Adrenal Axis Hypersuppression Is Associated with Gastrointestinal Symptoms in Major Depression

BACKGROUND/AIMS: Gastrointestinal symptoms and hypothalamus-pituitary-adrenal (HPA) axis dysfunction are frequently observed in patients with major depression. The primary aim of the study was to investigate the relationship between HPA-axis function and self-perceived functional gastrointestinal symptoms in major depression. METHODS: Patients with major depression (n = 73) and controls representative of the general population (n = 146) underwent a weight-adjusted very low dose dexamethasone suppression test (DST). Patients and controls completed the gastrointestinal symptom rating scale-iritable bowel syndrome (GSRS-IBS) and the hospital anxiety depression scale. Medical records of the patients were screened over a ten year period for functional gastrointestinal disorder and pain conditions. RESULTS: Patients with high GSRS-IBS scores (above median) exhibited HPA-axis hypersuppression more often than controls (defined by the lowest 10% cutoff of the post-DST cortisol values among controls, adjusted OR 7.25, CI 1.97-26.7) whereas patients with low GSRS-IBS scores did not differ from controls concerning their post-DST cortisol values. Patients who had consulted primary care for functional gastrointestinal disorder (P = 0.039), lumbago (P = 0.006) and chronic multifocal pain (P = 0.057) also exhibited an increased frequency of hypersuppression. CONCLUSIONS: HPA-axis hypersuppression is associated with functional gastrointestinal symptoms in patients with major depression.

Changes in common chemical signal molecules of neuroendocrine-immune network and intervention of Tongxinluo in rats under hypoxia qi-asthenia condition / 第二军医大学学报

Objective: To investigate the changes in common chemical signal molecules of neuroendocrine-immune (NEI) network and intervention of Tongxinluo (TXL, ultramicro-pulverization) of rats under hypoxia qi-asthenia condition. Methods: Forty-five male Wistar rats were randomly assigned to the following groups: control group, qi-asthenia model group and TXL group (n=15). The rats in the former 2 groups were gavaged with CMC-Na (10 ml/ kg) once daily; those in the TXL group were gavaged with TXL (ultramicrot-pulverization) suspended in CMC-Na (10 ml/kg) once daily; After gavage, animals in the qi-asthenia model group and TXL group were placed in a cabin with normal pressure hypoxia (7 h daily, 6 d weekly for 5 weeks). At the end of the experiment, the biological characters of rats were observed and arterial blood gas was analyzed. The serum contents of serotonin (5-HT), norepinephrine (NE), epinephrine (E), dopamine (DA) and IFN-γ and TRH level in the hypothalamus were examined by enzyme linked immunosorbent assay (ELISA); the serum contents of corticosterone (Cort), T3,T4,IL-1β,TNF-α, and corticotropin release hormone(CRH) in the hypothalamus, and adrenocorticotropic hormone/thyroid stimulating hormone(ACTH/TSH) in the hypophysis cerebri were examined using radio-immunity method. Results: Compared with control group, the biological character scores of rats in the qi-asthenia model group were significantly bigher(P

Effects of cyproheptadine on hypothalamus-pituitary-gonad axis and calmodulin gene expression in rats / 中国药理学与毒理学杂志

AIM To study whether cyproheptadine(Cyp) affects endocrine functions in reproductive system with gender difference. METHODS Sixty SD rats were randomly distributed into 3 groups according to gender, respectively, and they were administered NS(5 mL*kg-1*d-1), Cyp 2.4, 4.8 mg*kg-1*d-1 accordingly by ig for 14 d or 21 d. The serum levels of luteinizing hormone(LH), follicle stimulating hormone(FSH), testosterone(T), progesterone(P), estrodiol(E2) were measured by radio-immunoassay and the ultrastructure of gonadotropin-releasing hormone(GnRH) cells, gonadotropin cells, Leydig cells, Sertoli cells, luteal cells, granulocytes and so on were observed by electronmicroscopy and microscopy. The calmodulin(CaM) mRNA expression in hypothalamus-pituitary-testis axis(HPTA) was detected by reverse transcriptase-polymerase chain reaction. RESULTS Cyp(2.4 mg*kg-1*d-1×14 d, ig) increased serum LH concentration while decreased serum FSH, P concentrations in female rats. Cyp(4.8 mg*kg-1*d-1×14 d, ig)increased serum LH, T concentrations in males, and increased serum LH concentration while decreased serum FSH, E2 and P concentrations significantly in females. The retrograde changes of ultrastructure were observed in part of gonadotropin and ovary endocrine cells, while a stimulating one in testis endocrine cells. CaM mRNA expression levels were elevated in testis but not in hypothalamus and pituitary in male rats. CONCLUSIONCyp had a negative effect on endocrine function in females, but a positive one in males. The ultrastructure showed relevant changes in target gland. Cyp promoted CaM mRNA expression in testis,which had close connections with Cyp′s stimulative effect in HPTA.

Research on the hypothalamic-pituitary-ovary axis function in female patients with hepatolenticular degeneration / 中华神经科杂志

Objective To study the hypothalamic-pituitary-ovary axis function in female patients with hepatolenticular degeneration (HLD). Method By RIA test the levels of serum pituitary and sex hormones were observed. Results The level of fallicle-stimulating hormone (FSH) was significantly lower than that in control group ( P

Regulation of ‘Tiao Gan Fang Yao’ on neuroendocrine-immuno-function of bandage-stressed rats / 中国病理生理杂志

AIM: To investigate the regulation of ‘Tiao Gan Fang Yao’(TGFY) on neuroendocrine-immuno-function of bandage-stressed rat . METHODS:The stressed rat model was made by bandage. RIA was adopted to measure the function of hypothalamus-pitutary-adrenal gland axis (HPAA) of stressed rat. Meanwhile, the immunity of stressed rat and the regulation of TGFY were observed.RESULTS:Bandage stress increased the contents of serum corticosterone(CORT), and ACTH, and hypothalamus corticotropin releasing hormone ( P

Molecular biological responses to severe posttraumatic stress / 中国病理生理杂志

Traumatic stress in the normal individual results in activation of the sympatho-adrenal system causing a rise in noradrenaline and adrenaline, acute phase response in liver ,and activation of the hypothalamic-pituitary-adrenocortical(HPA)system resulting in elevated levels of cortisol. Studies in animals and in humans with posttraumatic stress disorder indicate that successful adaptation to stress is a prerequisite for the survival of all organisms living in an enviroment in which noxious stimuli are constantly present.