Corticotropin-releasing Hormone Levels Research Articles

Correlations of diurnal brain functional variations with serum biomarkers and objective sleep quality in patients with chronic insomnia disorder

Objectives: To investigate the correlations of diurnal brain functional variations with serum biomarkers and objective sleep quality in patients with chronic insomnia disorder (CID). Methods: A total of 60 CID patients and 30 healthy sleep volunteers who visited Department of Sleep Disorders of Chaohu Hospital affiliated to Anhui Medical University from March 2018 to June 2019 were collected. Diurnal brain function state was evaluated by Quantitative Measurement System of Brain Functional Status, and serum concentrations of corticotropin-releasing hormone (CRH) and glial fibrous acidic protein (GFAP) were detected using enzyme-linked immunosorbent assay (ELISA). The sleep quality in the CID group was evaluated using ploysomnography (PSG) at the same time. The brain function status indicators with significant changes in CID group were acquired, and the consistency of these indicators with serum biological markers and objective sleep quality was analyzed. Results: There were 23 males and 37 females in chronic in somnia patients; 15 males and 15 females in the healthy control group. Compared with the healthy controls, four brain function indicators of CID patients increased (brain inertia (196.0(163.0, 258.0)vs 168.5(148.8,182.5)), brain chaos (5.0(1.0, 10.0)vs 0(0,2.0)), internal concentration (31.0(13.0, 45.0)vs 2.0(0,27.5)) and endogenous anxiety (12.0(4.0, 18.0)vs 0(0,6.5)), but one indicator decreased (brain inhibitory value (47.0(32.0, 58.0)vs 59.0(46.3,66.3))) (all P<0.05).The brain chaos value positively correlated with the serum GFAP level (r=0.374,P=0.006), and the brain inertia value positively correlated with the serum CRH level (r=0.299,P=0.031). The value of brain inhibition positively correlated with the sleep latency (r=0.284,P=0.042). However, the values of internal concentration negatively correlated with the sleep efficiency (r=-0.276,P=0.048) and the time in non-rapid eye movement sleep stage 1 (r=-0.341, P=0.024). Conclusion: The brain waves of CID patients show significant changes in their brain function indicators, which are related to serum biological markers and objective sleep quality.

Chapter 7 - The supraoptic and paraventricular nuclei in healthy aging and neurodegeneration

The supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus undergo structural and functional changes over the course of healthy aging. These nuclei and their connections are also heterogeneously affected by several different neurodegenerative diseases. This chapter reviews the involvement of the SON and PVN, the hypothalamic-pituitary axes, and the peptide hormones produced in both nuclei in healthy aging and in neurodegeneration, with a focus on Alzheimer's disease (AD), frontotemporal dementia (FTD), amyotrophic lateral sclerosis, progressive supranuclear palsy, Parkinson's disease (PD), dementia with Lewy bodies (DLB), multiple system atrophy, and Huntington's disease. Although age-related changes occur in several regions of the hypothalamus, the SON and PVN are relatively preserved during aging and in many neurodegenerative disorders. With aging, these nuclei do undergo some sexually dimorphic changes including changes in size and levels of vasopressin and corticotropin-releasing hormone, likely due to age-related changes in sex hormones. In contrast, oxytocinergic cells and circulating levels of thyrotropin-releasing hormone remain stable. A relative resistance to many forms of neurodegenerative pathology is also observed, in comparison to other hypothalamic and brain regions. Mirroring the pattern observed in aging, pathologic hallmarks of AD, and some subtypes of FTD are observed in the PVN, though to a milder degree than are observed in other brain regions, while the SON is relatively spared. In contrast, the SON appears more vulnerable to alpha-synuclein pathology of DLB and PD. The consequences of these alterations may help to inform several of the physiologic changes observed in aging and neurodegenerative disease.

Association of biomarkers of exposure to metals and metalloids with maternal hormones in pregnant women from Puerto Rico

BackgroundMetal(loid)s have been associated to adverse birth outcomes in experimental and epidemiological studies, but the underlying mechanism(s) are not well understood. Endocrine disruption may be a mechanism by which the metal(loid)s impact birth outcomes. MethodsPregnant women were recruited through the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT). Urine, blood, demographic and pregnancy-related data were collected at recruitment and subsequent visits. Sixteen metal(loid)s were analyzed in urine and blood samples, while nine maternal hormones (corticotropin-releasing hormone (CRH), sex-hormone binding globulin (SHBG), estriol (E3), progesterone, testosterone, thyroid-stimulating hormone (TSH), total triiodothyronine (T3), total thyroxine (T4), and free thyroxine (fT4)) were measured in serum samples from 815 singleton pregnancies. Linear mixed models with random intercepts were used to examine associations between metal(loid)s in blood and urine with hormone concentrations. ResultsArsenic blood concentrations were significantly associated with increased levels in CRH (%Δ: 23.0, 95%CI: 8.4–39.6) and decreased levels in testosterone (%Δ: −16.3, 95%CI: −26.2-−5.1). Cobalt, manganese, and lead blood concentrations were associated with small increases in SHBG (%Δ range: 3.3–4.2), E3 (%Δ range: 3.9–8.7) and progesterone (%Δ range: 4.1–6.3) levels, respectively. Nickel blood concentration was inversely associated with testosterone levels (%Δ −13.3, 95%CI: −18.7-−7.6). Significant interactions were detected for the association between nickel and study visit in relation to CRH (p < 0.02) and testosterone levels (p < 0.01). ConclusionOur analysis suggests that metal(loid)s may act as endocrine disruptors by altering prenatal hormone levels. This disruption may depend on specific windows of exposure during pregnancy. Additionally, some essential metal(loid)s such as managense and cobalt may be contributors to adverse maternal and fetal outcomes. The study of metal(loid)s as endocrine disruptors is in the early stages of epidemiological research and future studies are needed to further investigate these associations.

Placental Corticotrophin-Releasing Hormone is a Modulator of Fetal Liver Blood Perfusion.

Variation in fetal liver blood flow influences fetal growth and postnatal body composition. Placental corticotrophin-releasing hormone has been implicated as a key mediator of placental-fetal perfusion. To determine whether circulating levels of placental corticotrophin-releasing hormone across gestation are associated with variations in fetal liver blood flow. Prospective cohort study. Fetal ultrasonography was performed at 30 weeks' gestation to characterize fetal liver blood flow (quantified by subtracting ductus venosus flow from umbilical vein flow). Placental corticotrophin-releasing hormone was measured in maternal circulation at approximately 12, 20, and 30 weeks' gestation. Multiple regression analysis was used to determine the proportion of variation in fetal liver blood flow explained by placental corticotrophin-releasing hormone. Covariates included maternal age, parity, pre-pregnancy body mass index, gestational weight gain, and fetal sex. A total of 79 uncomplicated singleton pregnancies were analyzed. Fetal liver blood flow was 68.4 ± 36.0 mL/min (mean ± SD). Placental corticotrophin-releasing hormone concentrations at 12, 20, and 30 weeks were 12.5 ± 8.1, 35.7 ± 24.5, and 247.9 ± 167.8 pg/mL, respectively. Placental corticotrophin-releasing hormone at 30 weeks, but not at 12 and 20 weeks, was significantly and positively associated with fetal liver blood flow at 30 weeks (r = 0.319; P = 0.004) and explained 10.4% of the variance in fetal liver blood flow. Placental corticotrophin-releasing hormone in late gestation is a possible modulator of fetal liver blood flow and may constitute a biochemical marker in clinical investigations of fetal growth and body composition.

Corticosterone induced apoptosis of mouse oviduct epithelial cells independent of the TNF-α system.

It has been reported in recent studies that restraint stress on pregnant mice during the preimplantation stage elevated corticotrophin-releasing hormone (CRH) and glucocorticoid levels in the serum and oviducts; furthermore, CRH and corticosterone (CORT) impacted preimplantation embryos indirectly by triggering the apoptosis of oviductal epithelial cells (OECs) through activation of the Fas system. However, it remains unclear whether TNF-α signaling is involved in CRH- and/or glucocorticoid-induced apoptosis of OECs. In the present study, it was shown that culture with either CRH or CORT induced significant apoptosis of OECs. The culture of OECs with CRH augmented both FasL expression and TNF-α expression. However, culture with CORT increased FasL, but decreased TNF-α, expression significantly. Although knocking down/knocking out FasL expression in OECs significantly ameliorated the proapoptotic effects of both CRH and CORT, knocking down/knocking out TNF-α expression relieved only the proapoptotic effect of CRH but not that of CORT. Taken together, our results demonstrated that CRH-induced OEC apoptosis involved both Fas signaling and TNF-α signaling. Conversely, CORT-induced OEC apoptosis involved only the Fas, but not the TNF-α, signaling pathway. The data obtained are crucial for our understanding of the mechanisms by which various categories of stress imposed on pregnant females impair embryo development, as well as for the development of measures to protect the embryo from the adverse effects of stress.

Comprehensive chemical analysis of Zhenshu Tiaozhi formula and its effect on ameliorating glucolipid metabolic disorders in diabetic rats

The present study aims to reveal the compositions of Zhenshu TiaoZhi formula (FTZ) comprehensively, and investigate whether FTZ ameliorate glucolipid metabolism disorders in diabetic rats with the involvement of glucocorticoids in peripheral insulin-sensitive tissues.The fingerprint was established based on 11 batches of FTZ samples and chemical compostions of FTZ were identified by ultra performance liquid chromatography-time of flight/mass spectrometry (UPLC-TOF/MS). High-fat diet (HFD) and streptozotocin (STZ) induced diabetic rats were orally administrated with 3 and 6 g/kg body weight of FTZ for 8 weeks. Indices of glucolipid metabolism, including fasting blood glucose (FBG), fasting insulin, insulin resistance index (IRI) and blood lipids were evaluated after treatment of FTZ. The levels of HPA axis hormones were examined. Reverse transcription-polymerase chain reaction (RT-PCR) was adopted to investigate the relative mRNA expressions of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) and glucolipid metabolic indicators.A reference fingerprint was established and 93 compounds of FTZ were tentatively identified. In vivo, FTZ treatment exerted antidiabetic and antidyslipidemic effects while decreased the level of corticotropin releasing hormone (CRH). 11β-HSD1 mRNA showed similar trajectory in both liver, adipose and skeletal muscle tissues, which was up-regulated in diabetic group and ameliorated in FTZ groups. Furthermore, the expressions of glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK) and adipose triglyceride lipase (ATGL) were down-regulated in liver and skeletal muscle.These results elucidated the compositions of FTZ comprehensively and indicated its effect on ameliorating glucolipid metabolism of diabetic rats involved hypothalamus-pituitary-adrenal (HPA) axis homeostasis. Down-regulating 11β-HSD1 in insulin-sensitive tissues might be a potential mechanism of FTZ in treating type 2 diabetes mellitus (T2DM).

Macrophage-activating lipopeptide-2 and corticotropin-releasing hormone stimulate the inflammatory signalling in human sebocytes through activation of stearoyl-CoA desaturase and fatty acid desaturase 2.

The macrophage-activating lipopeptide-2 (MALP-2) activates cells carrying a functional Toll-like receptor (TLR)-2/6. Human sebocytes express functional TLR-2, TLR-4 and CD14. Upregulation of stearoyl-CoA desaturase (SCD) and fatty acid desaturase-2 (FADS2) expression induces pro-inflammatory sebaceous activity. On the other hand, corticotropin-releasing hormone (CRH) is likely to serve as an autocrine stress hormone in human sebocytes. In addition to its antiproliferative, lipogenetic and androgen-activating functions, CRH exhibits a pro-inflammatory action and its expression is upregulated in acne-involved sebaceous glands. Determination of the pro-inflammatory function of MALP-2 and CRH and clarification of the option that MALP-2 and/or CRH activity on human sebocytes might be mediated through SCD and/or FADS2. SZ95 sebocytes were treated with MALP-2, CRH and the SCD inhibitor/ligand FPCA. SCD, FADS2, TLR-2 mRNA and protein levels and IL-6 and IL-8 secretion were investigated. Intracellular CRH levels were assessed under treatment with CRH, MALP-2, linoleic acid and arachidonic acid. Phorbol 12-myristate 13-acetate and dexamethasone served as positive and negative controls, respectively. MALP-2 upregulated SCD, FADS2, TLR-2 mRNA and protein levels and IL-6 and IL-8 secretion from SZ95 sebocytes. Co-incubation of SZ95 sebocytes with MALP-2/FPCA did not affect the MALP-2-induced SCD mRNA upregulation but reduced FADS2 mRNA levels and inhibited IL-8 secretion. CRH induced an early, low-level SCD and FADS2 upregulation and TLR-2 and IL-8 secretion. High intracellular CRH concentrations could be detected early after CRH treatment and persisted up to 24h. MALP-2 stimulated intracellular CRH levels. MALP-2 stimulates the inflammatory signalling in human sebocytes through SCD and FADS2 activation. Inhibition of FADS2 mRNA levels and IL-8 secretion through MALP-2/FCPA co-incubation and diminution of fatty acid unsaturation might lead to a reduction of pro-inflammatory sebaceous lipids. CRH upregulates inflammatory signalling via the SCD/FADS2 pathway, and MALP-2 selectively enhances CRH levels in human sebocytes.

Investigating apoptotic, inflammatory, and growth markers in poor responders undergoing natural in vitro fertilization cycles: a pilot study.

This study investigates follicular fluid (FF) from patients with poor and normal ovarian response undergoing natural assisted reproductive technology cycles. We report about (1) cell-free DNA (cfDNA), which reflects apoptosis; (2) corticotropin-releasing hormone (CRH); (3) interleukin (IL)-15, which reflects inflammation; (4) granulocyte colony-stimulating factor (G-CSF); (5) vascular endothelial growth factor (VEGF); and (6) insulin-like growth factor I (IGF-I), which reflects follicular growth. Forty-four poor responders and 44 normal responders-according to the Bologna criteria-were recruited. FF samples were prepared for cfDNA quantification employing Q-PCR and for CRH, IL-15, G-CSF, VEGF, and IGF-I quantification employing ELISA. Statistically nonsignificant different levels of FF cfDNA, CRH, IL-15, VEGF, and IGF-I were observed. Interestingly, statistically significant higher G-CSF levels were observed in normal responders (302.48 ± 474.36 versus 200.10 ± 426.79 pg/mL, P=0.003). Lower cfDNA integrity was observed in cycles resulting in clinical pregnancy for both groups (normal: 0.07 ± 0.04 versus 0.25 ± 0.17 ng/μL, P < 0.001; poor: 0.10 ± 0.06 versus 0.26 ± 0.12 ng/μL, P < 0.001). The results predominantly showcase similarities between normal and poor responders pertaining to inflammatory, apoptotic, and growth factors. This may be attributed to the employment of natural cycles in order to exclude controlled ovarian stimulation as a factor-indicating its detrimental effect. As G-CSF levels presented significantly higher in normal responders, its vital role in understanding a compromised ovarian response is highlighted.

Shizhenqing granule stimulates the hypothalamic-pituitary-adrenal axis and reduces serum pro-inflammatory factors in a rat model with chronic eczema

In this study, we examined the effects of Shizhenqing granule (SZQG) on hypothalamic-pituitary-adrenal (HPA) axis and serum inflammatory factors in a rat model of chronic eczema, in order to explore the mechanism of action of SZQG in treatment of this disease. Sixty Sprague–Dawley male rats were randomly divided into six groups (with 10 rats per group): blank group; model group; positive control group (prednisone); and the low-, medium-, and high-dose SZQG groups. Except for the blank group, rats in all other groups were treated with 2,4-dinitrochlorobenzene to induce chronic eczema. These rats were administered prednisone or SZQG for 7 consecutive days after successful establishment of the chronic eczema model, and samples were collected 12 h after the last administration. The degree of skin lesions and the changes in serum levels of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), cortisol (CORT), interleukin (IL)-4, interferon (IFN)-γ, IL-25, and IL-31 among the groups were compared. SZQG effectively increased the levels of CRH, ACTH, and CORT, which decreased in the serum of rats with chronic eczema, stimulated the function of the HPA axis, and promoted the expression of glucocorticoids. SZQG reduced the serum levels of inflammatory factors including IL-4, IL-25 and IL-31, which were overexpressed in rats with chronic eczema, and increased those of anti-inflammatory factor IFN-γ, thereby alleviating the inflammatory symptoms and itching, and ameliorating the clinical symptoms of chronic eczema. SZQG effectively alleviates skin lesions in the chronic eczema rat model by stimulating the function of the HPA axis.

Acupuncture in addition to budesonide does not further improve RQLQ apart from the sleep domain

BACKGROUND: Acupuncture can effectively alleviate the nasal symptoms of allergic rhinitis (AR); however, the mechanism is unclear. Previous studies suggested it may be related to improve hypothalamus-pituitary-adrenal (HPA) axis dysfunction. MATERIALS and METHODS: The study was a randomised controlled trial including ninety patients with moderate to severe persis- tent AR. Subjects were randomised 1:1:1 to the 8-weeks treatment with mind-regulating acupuncture combined with intranasal glucocorticosteroids (INGC), conventional acupuncture combined with INGC and INGC alone (MA, CA, GC respectively). The primary outcome was the change from baseline in the Visual Analogue Scale (VAS) score of nasal symptoms. Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score was a key secondary outcome. The levels of corticotrophin releasing hormone (CRH), cortisol (COR) and adrenocorticotropic hormone (ACTH) were also analysed. RESULTS: MA, CA and GC reduced VAS score and total RQLQ by a similar degree, but the sleep domain of RQLQ significantly impro- ved in MA and CA compared to GC. Meanwhile, the COR and ACTH level increased, and CRH level decreased after treatment in MA and CA, but the changes showed no difference among the three groups after Bonferroni correction. CONCLUSIONS: Although acupuncture combined with INGC may have potential effect on sleep quality, the combination therapy cannot further improve nasal symptoms or RQLQ compared to INGC alone in AR patients. The influence of acupuncture on HPA axis needs to be further explored.

Psychosocial Stressors in Relation to Maternal Plasma Levels of Corticotrophin Releasing Hormone (CRH) During Pregnancy

Background: Psychosocial stress during pregnancy has been associated with a number of adverse birth outcomes, including preterm birth. However, we have a limited understanding of the biologic pathways that might link stress to adverse outcomes. Corticotrophin Releasing Hormone (CRH) may represent one possible mechanism, as elevated levels of CRH have been associated with preterm birth. The purpose of this study was to examine the relationships between maternal self-reported psychosocial stress and CRH during pregnancy. We hypothesized that women who experienced psychosocial stress would have elevated levels of CRH. Methods: Women were enrolled in the Chemicals in Our Bodies-2 cohort (N=496), a demographically diverse cohort of pregnant women in San Francisco. CRH (pg/mL) was measured in plasma obtained at the 2nd trimester visit. Psychosocial stress was assessed via self-reported questionnaire at the 2nd trimester and included dichotomous measures of neighborhood quality, stressful life events, caregiving, discrimination, financial strain, job strain, food insecurity, unplanned pregnancy, perceived stress, depression, and perceived community status. Linear regression was used to examine associations between psychosocial stressors and CRH. Results: Experiencing &gt;2 stressful life events was associated with elevated levels of CRH after adjusting for gestational age at visit, maternal race/ethnicity, maternal education, and marital status (β=0.16, 95% confidence interval [CI]=0.02, 0.31). Women who experienced financial strain (β=0.13, 95% CI=-0.10, 0.36), caregiving for an ill family member (β=0.13, 95% CI=-0.06, 0.32), or who had elevated levels of perceived stress (β=0.20, 95% CI=-0.20, 0.41) also had moderately increased CRH levels. No associations were observed between other psychosocial stressor and CRH levels. Conclusions: We observed a positive association between stressful life events and elevated CRH levels in our study population. Future research should explore the combined effects of psychosocial stress and chemicals on birth outcomes and examine CRH as a mediator of the psychosocial stress and birth outcomes relationships.

Maternal exposure to childhood traumatic events, but not multi-domain psychosocial stressors, predict placental corticotrophin releasing hormone across pregnancy.

Maternal psychosocial stress increases the risk of adverse birth and postnatal outcomes for the mother and child, but the role of maternal exposure to childhood traumatic events (CTE) and multi-domain psychosocial stressors for the level and rise of placental Corticotrophin-Releasing Hormone (pCRH) across pregnancy has been understudied. In a sociodemographically and racially diverse sample of 1303 women (64% Black, 36% White/others) with low-medical risk pregnancies at enrollment from Shelby County, Tennessee, USA, blood samples were drawn twice, corresponding roughly to second and third trimester, and extracted prior to conducting radioimmune assays for pCRH. Mothers reported CTE (physical abuse, sexual abuse, or family violence, in childhood), adulthood traumatic events, and interpersonal violence during pregnancy. Neighborhood crime/deprivation was derived using geospatially-linked objective databases. General linear and mixed models tested associations between stress exposure variables and pCRH levels and rate of rise, adjusting for obstetric/clinical/health related factors. Maternal CTE did not predict pCRH levels at time 1, but positively predicted levels at time 2, and the rate of rise in pCRH across pregnancy. Race did not moderate this association. No additional maternal stress exposures across adulthood or during pregnancy predicted pCRH outcomes. Findings indicate that childhood violence or abuse exposure can become biologically embedded in a manner predicting later prenatal physiology relevant for maternal and offspring health, and that such embedding may be specific to childhood, but not adulthood, stress. Findings also highlight the placental-fetal unit as a mechanistic pathway through which intergenerational transmission of the adverse effects of childhood adversities may occur.

Sex-Dependent Pathology in the HPA Axis at a Sub-acute Period After Experimental Traumatic Brain Injury.

Over 2.8 million traumatic brain injuries (TBIs) are reported in the United States annually, of which, over 75% are mild TBIs with diffuse axonal injury (DAI) as the primary pathology. TBI instigates a stress response that stimulates the hypothalamic-pituitary-adrenal (HPA) axis concurrently with DAI in brain regions responsible for feedback regulation. While the incidence of affective symptoms is high in both men and women, presentation is more prevalent and severe in women. Few studies have longitudinally evaluated the etiology underlying late-onset affective symptoms after mild TBI and even fewer have included females in the experimental design. In the experimental TBI model employed in this study, evidence of chronic HPA dysregulation has been reported at 2 months post-injury in male rats, with peak neuropathology in other regions of the brain at 7 days post-injury (DPI). We predicted that mechanisms leading to dysregulation of the HPA axis in male and female rats would be most evident at 7 DPI, the sub-acute time point. Young adult age-matched male and naturally cycling female Sprague Dawley rats were subjected to midline fluid percussion injury (mFPI) or sham surgery. Corticotropin releasing hormone, gliosis, and glucocorticoid receptor (GR) levels were evaluated in the hypothalamus and hippocampus, along with baseline plasma adrenocorticotropic hormone (ACTH) and adrenal gland weights. Microglial response in the paraventricular nucleus of the hypothalamus indicated mild neuroinflammation in males compared to sex-matched shams, but not females. Evidence of microglia activation in the dentate gyrus of the hippocampus was robust in both sexes compared with uninjured shams and there was evidence of a significant interaction between sex and injury regarding microglial cell count. GFAP intensity and astrocyte numbers increased as a function of injury, indicative of astrocytosis. GR protein levels were elevated 30% in the hippocampus of females in comparison to sex-matched shams. These data indicate sex-differences in sub-acute pathophysiology following DAI that precede late-onset HPA axis dysregulation. Further understanding of the etiology leading up to late-onset HPA axis dysregulation following DAI could identify targets to stabilize feedback, attenuate symptoms, and improve efficacy of rehabilitation and overall recovery.

Maternal Sodium Valproate Exposure Alters Neuroendocrine-Cytokines and Oxido-inflammatory Axes in Neonatal Albino Rats.

The aim of the study was to determine the influence of maternal sodium valproate (SVP) on neonatal neuroendocrine (hypothalamic-pituitary-adrenal; HPA)-cytokines and oxido-inflammatory axes. Pregnant rats (Rattus norvegicus) were orally administered (by gavage) SVP (50 mg/kg) from gestation day (GD) 8 to lactation day (LD) 21. The elevation in serum corticotropin-releasing hormone (CRH), corticosterone, and adrenocorticotropic hormone (ACTH) levels was highly significant at postnatal days (PNDs) 14 and 21 in both dams and neonates of the maternal SVP-treated group relative to those in the control group. However, hypercortisolism (cortisolemia) was highly significant in neonates at both PNDs 14 and 21, while in dams, it was not significantly increased at LD 14 but was at LD 21. This disruption caused adverse effects on maternal food consumption and maternal/neonatal body weight. The maternal SVP treatment resulted in higher levels of neonatal serum adrenaline, noradrenaline, neuropeptide Y (NPY), tumor necrosis factor-alpha (TNF-α), leptin, interleukins (IL-1β, IL-17, IL-4, IL-6 & IL-2), transforming growth factor-beta (TGF-β), and prostaglandin E2 (PGE2), and lower levels of neonatal serum growth hormone (GH), insulin growth factor-1 (IGF-1) and adiponectin at both PNDs. This administration also induced the oxidative stress in neonatal cerebrum and cerebellum at both tested PNDs via the production of free radicals (malondialdehyde; MDA & nitric oxide; NO) and reduction of antioxidant parameters (glutathione; GSH, superoxide dismutase; SOD & catalase; CAT). Maternal SVP treatment stimulated the neonatal stress-brain (HPA) axis, resulted in an oxido-inflammatory state, and disrupted the neuroendocrine-cytokines axis, and generally neonatal health.

Influence of labor on direct and indirect determinants of placental 11beta-hydroxysteroid dehydrogenase activity

PurposeLabor is a complex process involving multiple para-, auto- and endocrine cascades. The interaction of cortisol, corticotropin-releasing hormone (CRH) and progesterone is essential. The action of cortisol on the human feto-placental unit is regulated by 11beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2/HSD11B2) that converts cortisol into inactive cortisone. The majority of studies on the assessment of placental 11β-HSD2 function determined indirect activity parameters. It remains elusive if indirect measurements correlate with enzymatic function and if these parameters are affected by potential confounders (e.g., mode of delivery). Thus, we compared determinants of indirect 11β-HSD2 tissue activity with its direct enzymatic turnover rate in placental samples from spontaneous births and cesarean (C)-sections.MethodsUsing LC–MS/MS, we determined CRH, cortisol, cortisone, progesterone and 17-hydroxy(OH)-progesterone in human term placentas (spontaneous birth vs. C-section, n = 5 each) and measured the enzymatic glucocorticoid conversion rates in placental microsomes. Expression of HSD11B1, 2 and CRH was determined via qRT-PCR in the same samples.ResultsCortisol–cortisone ratio correlated with direct microsomal enzymatic turnover. While this observation seemed independent of sampling site, a strong influence of mode of delivery on tissue steroids was observed. The mRNA expression of HSD11B2 correlated with indirect and direct cortisol turnover rates in C-section placentas only. In contrast to C-sections, CRH, cortisol and cortisone levels were significantly increased in placental samples following spontaneous birth.ConclusionLabor involves a series of complex hormonal processes including activation of placental CRH and glucocorticoid metabolism. This has to be taken into account when selecting human cohorts for comparative analysis of placental steroids.

Effects of varying intensities of heat stress on neuropeptide Y and proopiomelanocortin mRNA expression in rats.

The aim of the present study was to investigate the effects of varying intensities of heat stress on the mRNA expression levels of neuropeptide Y (NPY), proopiomelanocortin (POMC) and stress hormones in rats. To establish a rat model of heat stress, the temperature and time were adjusted in a specialized heating chamber. Sprague-Dawley (SD) rats were randomly divided into four groups; control (CN; temperature, 24±1˚C); moderate strength 6 h (MS6; temperature, 32±1˚C time, 6 h), moderate strength 24 h (MS24; temperature, 32±1˚C; time, 24 h) and high strength 6 h (HS6; temperature, 38±1˚C; time, 6 h) groups. SD rats were exposed to heat for 14 consecutive days. The levels of heat stress-related factors, including corticotropin-releasing hormone (CRH), cortisol (COR), epinephrine (EPI) and heat shock protein 70 (HSP70), were measured in the rat blood using ELISA. In addition, the weight of the spleen, thymus, hypophysis and hypothalamus were determined. The mRNA expressions levels of NPY and POMC were detected using quantitative PCR. The results showed that the CRH, COR and HSP70 levels were increased in the three heat stress groups compared with the CN group. Notably, the levels of CRH, EPI and HSP70 were increased in the HS6 group compared with the CN and MS6 groups (P<0.05). Furthermore, the weights of the hypophysis and hypothalamus in the HS6 group were significantly lower compared with the CN group (P<0.05). In addition, NPY and POMC expression levels were downregulated in the MS24 group compared with the CN group. The mRNA expression levels of NPY and POMC were altered in response to different intensities of heat stress. Therefore, their levels were downregulated and upregulated following long-time and moderate-time heat exposure, respectively. The results of the present study suggested that the reduced mRNA expression levels of NPY may be partially responsible for the heat-induced injuries in rats following long-time heat exposure.

Heat stress decreases egg production of laying hens by inducing apoptosis of follicular cells via activating the FasL/Fas and TNF-α systems

Heat stress (HS) causes significant economic losses in the poultry industry every year. However, the mechanisms for the adverse effects of HS on avian follicular development are largely unknown. The aim of this study was to test whether HS induces apoptosis of follicular cells and impairs egg production by activating the FasL/Fas and tumor necrosis factor (TNF)-α systems. To this end, Hy-Line Brown laying hens, at 32 wk of age, were either exposed to HS of 35°C to 37°C or maintained at 24°C to 26°C (control) for 5 D. At the end of the HS period, follicle numbers, apoptosis, FasL/Fas and TNF-α activation, oxidative stress, and hormone secretion were examined in ovarian follicles. Egg production was observed daily during both the stressed (day S1–S5) and the poststress recovery (day R1–R15) periods. The results demonstrated that HS on hens significantly 1) decreased laying rates from day S3 to R6; 2) reduced numbers of large yellow and hierarchical follicles; 3) triggered apoptosis while increasing the expression of FasL, Fas, TNF-α, and TNF-receptor 1 in small and large yellow follicles; and 4) increased levels of oxidative stress, corticotrophin-releasing hormone, and corticosterone while decreasing the estradiol/progesterone ratio in follicular fluid in small and large yellow follicles. Taken together, the results suggested that hen HS impaired egg production by reducing the number of follicles through inducing apoptosis and that it triggered apoptosis in follicular cells by activating the FasL/Fas and TNF-α systems.

Quercetin attenuates endocrine and metabolic responses to oxytetracycline in silver catfish (Rhamdia quelen)

This study aimed to verify whether dietary quercetin protects against the detrimental effects induced by oxytetracycline (OTC) administration in silver catfish (Rhamdia quelen). Fish were divided into different experimental groups that received OTC and/or quercetin, either during 14 or 21 days. To determine the endocrine system stress response, we have measured the brain mRNA expression levels of corticotropin-releasing hormone (crh), proopiomelanocortins (pomca and pomcb) and some of the pituitary hormones (growth hormone [gh], somatolactin [sl], and prolactin [prl]). We have also quantified the levels of cortisol as well as some metabolites (glucose, glycogen, lactate, and triglycerides) in the plasma. Moreover, the enzymatic activity of hexokinase, phosphorylase (active GPase), fructose-biphosphatase (FBP), glycerol-3-phosphate dehydrogenase, glucose-6-phosphate dehydrogenase, and glutamate dehydrogenase (GDH) and gill Na+/K+-ATPase were measured. The results demonstrated that OTC activates the silver catfish stress response by increasing the plasma cortisol and decreasing the glucose levels at 14 and 21 days. Additionally, OTC also altered the fish hepatic metabolic status as demonstrated by an increase in triglycerides levels and the enzymatic activity of both FBP and GDH after 14 days. OTC also stimulated Na+/K+-ATPase activity in the gill after 14 days and altered the hypophyseal expression of gh (at 14 and 21 days) and prl (at 14 days). The co-treatment with 1.5 g of quercetin could prevent most of the alterations caused by OTC, strongly suggesting quercetin as a beneficial compound when added to the fish diet.

Effect of Tongdu Tiaoshen needling in treatment of chronic insomnia by regulating the hypothalamic-pituitary-adrenal axis

To investigate the clinical effect of Tongdu Tiaoshen needling in the treatment of chronic insomnia and its mechanism based on the hypothalamic-pituitary-adrenal (HPA) axis. A total of 60 patients with chronic insomnia were randomly divided into treatment group and control group, with 30 patients in each group. In addition to the health education on sleep, the patients in the treatment group were given Tongdu Tiaoshen needling, i．e., electroacupuncture at Baihui (GV20), Shenting (GV24), Yintang (EX-HN3), bilateral Shenmen (HT7), and bilateral Sanyinjiao (SP6), and those in the control group were given superficial acupuncture at Shousanli (LI10), Futu (ST32), and Feiyang (BL58) at both sides, once every other day and three times a week for 4 consecutive weeks. Before and after treatment, the Pittsburgh Sleep Quality Index (PSQI) was used to assess the quality and efficiency of sleep, and ELISA was used to measure the serum levels of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone (CORT). After treatment, the treatment group had significant reductions in the total PSQI score and the score of each component of PSQI (P<0.01), and the control group had significant reductions in the total PSQI score (P<0.01) and the scores of all components except sleep duration (P<0.05); compared with the control group, the treatment group had significantly lower total PSQI score and the score of each component (P<0.01). After treatment, the treatment group had significant reductions in the serum levels of CRH, ACTH and CORT (P<0.05，P <0.01), and compared with the control group, the treatment group had significant reductions in the serum levels of CRH, ACTH and CORT (P<0.01，P<0.05). Tongdu Tiaoshen needling has a good clinical effect in the treatment of chronic insomnia and can significantly improve the sleep condition of patients with chronic insomnia, possibly by reducing the hormones associated with the HPA axis.

Influence of early rearing environment on water-borne cortisol and expression of stress-related genes in grass carp (Ctenopharyngodon idella).

Nowadays, lower post-release survivorship of hatchery-reared fish in natural aquatic bodies has attained great attention and research is in progress to determine the reasons for their higher mortality. It is assumed that hatchery rearing environments negatively affect the physiological stress response of the fish. Thus, understanding how rearing environments modulate this is important for the well-being of fish. Here, an attempt has been made to assess the influence of two early rearing environments, i.e., barren (BR), mimic the conventional hatchery rearing environment; without any substrate and enrichment items and structurally enriched (ER), containing multi-colored gravel substrate, cobbles and plants, on the stress regulators i.e., HPI-axis and brain monoaminergic system of fish. Three-day old grass carp (Ctenopharyngodon idella) postlarvae were reared up to the fingerling stage in the aforementioned environments. For the stress assay, fish were subjected to net capture followed by 30min confinement in a small container at a lower water level. The pre- and post-stress responses were compared by evaluating their water-borne cortisol and the mRNA level of corticotropin releasing hormone (CRH), dopamine D1A receptor (DRD1A) and hydroxytryptamine receptor 2B (HTR2B) in the whole brain through qPCR analysis. Results of two-way ANOVA revealed significantly low (p < .001) post-stress concentration and release rate of water-borne cortisol and pre- and post-stress expression of CRH, DRD1A and HTR2B genes in the ER than BR fish. It is concluded that a structurally complex early rearing environment reduces the stress level in fish.