UNIPROT:P01189 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UNIPROT:P01189 (beta-endorphin)
21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Corticotropin releasing factor (CRF) binding protein (CRF-BP) was measured in media and cell lysates of primary rat astrocytes, microglia and neurons with the use of a ligand immunoradiometric assay (LIRMA). A low basal level of CRF-BP was detected in the media and cell lysates from primary neuronal and astrocyte cells after 48 h in culture. No basal expression of CRF-BP was detected in cell lysates or media from primary microglial cultures. The CRF-BP expressed in cultured astrocytes and neurons had the same pharmacological characteristics as the human recombinant molecule. After forskolin, IBMX or forskolin/IBMX treatment, a robust increase in secreted CRF-BP levels in the media from astrocytes and neurons, but not microglia, was observed. An increase in CRF-BP-like immunoreactivity in cell lysates was also observed after IBMX/forskolin treatment. In situ hybridization analysis revealed that CRF-BP mRNA was increased in primary cultured astrocytes after IBMX/forskolin stimulation suggesting that regulation was at the level of gene transcription. 'Axon sparing' lesions produced with 0.12 M quinolinic acid in PBS injected intracerebrally (unilaterally into dorsal hippocampus) resulted in loss of CRF-BP expression in neurons. These data provide evidence for the differential localization and regulation of CRF-BP in different cell types in brain and suggest that CRF-BP expression may be locally increased in disease states associated with astrocytosis and gliosis.
...
PMID:Corticotropin releasing factor binding protein (CRF-BP) is expressed in neuronal and astrocytic cells. 858 94

The present study was conducted to verify whether experimental conditions such as obesity and food deprivation, which promote food intake and reduce thermogenesis, could modify the expression of the corticotropin-releasing hormone (CRH)-binding protein (BP) in the rat brain. In situ hybridization, histochemistry, and immunohistochemistry were used to assess the expression of CRH-BP in lean (Fa/?) and obese (fa/fa) Zucker rats that were fed ad libitum, food deprived for 24 h, or food deprived for 24 h and refed for 6 h. In both lean and obese rats, food deprivation led to a reduction in body weight that was accompanied by a reversible increase in plasma corticosterone levels. Food deprivation and, to a lesser degree, obesity induced the expression of CRH-BP mRNA in the dorsal part of the medial preoptic area (MPOA). This induction of the CRH-BP gene led to by food deprivation was confirmed by the appearance in the dorsal part of the MPOA of neurons immunoreactive to CRH-BP. Food deprivation (in particular) and obesity also increased the levels of CRH-BP mRNA in the basolateral amygdala (BLA). The enhanced CRH-BP expression in the MPOA and BLA in response to food deprivation was reversed by refeeding. In lean Fa/? rats, the CRH-BP mRNA level in the pituitary cells was significantly decreased after food deprivation and restored after refeeding. When food was provided ad libitum, the number of cells expressing CRH-BP in the anterior pituitary was significantly higher in lean rats than in obese animals. Food deprivation for 24 h decreased dramatically the number of pituitary cells expressing CRH-BP in lean rats. Altogether, the present results demonstrate that food deprivation and, to a lesser extent, obesity can selectively affect the expression of CRH-BP. Given both the inactivating effect of CRH-BP on the CRH system and the potential roles played by the MPOA and BLA in the thermogenic and anorectic effects of CRH, it can be argued that the induction of the CRH-BP gene in obesity and after food deprivation occurs as a mechanism to reduce energy expenditure and to stimulate food intake.
...
PMID:Corticotropin-releasing hormone-binding protein in brain and pituitary of food-deprived obese (fa/fa) Zucker rats. 1060 Sep 23

The endocrine stress response is pivotal in vertebrate physiology. The stress hormone cortisol-the end product of the endocrine stress axis-(re-)directs energy flows for optimal performance under conditions where homeostasis may be or become at risk. Key players in the continuous adaptation process are corticotropin-releasing factor (CRF) from the hypothalamic nucleus preopticus (NPO), pituitary adrenocorticotropic hormone (ACTH) and cortisol produced by the interrenal cells in the headkidney (adrenal equivalent of fish). CRF is a member of a large family of related peptides that signals through CRF-receptor subtypes specific for central and peripheral actions of the peptide. CRF is "chaperoned" by a unique and phylogenetically very well-conserved binding protein (CRFBP); the functions of the CRFBP can only be speculated on so far, but its mRNA and protein abundance are important indicators of the central CRF-system activity, and indeed its mRNA levels are altered by restraint stress. Moreover, the unique structure and size of the CRFBP provide good tools in phylogenetic studies, that date the CRF-system to at least one billion years old. Pro-opiomelanocortin is produced and processed to ACTH and endorphin in the hypothalamic NPO and pituitary pars distalis ACTH-cells, to MSH and acetylated endorphins in the pituitary pars intermedia MSH-cells. ACTH is the prime corticotrope in acute stress conditions. In carp, MSH, considered a mild corticotrope in chronic stress responses in other fish, lacks corticotropic effects (in line with the absence of the melanocortin-5 receptor in headkidney); yet, an unknown corticotropic signal substance in the pars intermedia of carp awaits elucidation. Interesting observations were made on the CRF control of pituitary cells. CRF stimulates ACTH-cells, but only when these cells experience a mild dopaminergic block. Endorphin, produced in the NPO and transported via axons to the pituitary gland in vivo, reverses the stimulatory CRF action on MSH-cells to a differential inhibition of N-acetyl beta-endorphin release in vitro (MSH release is not affected). We speculate that the consistently observed elevation of plasma MSH during chronic stress may exert central actions related to feeding and leptin regulated processes. A BOLD-fMRI study revealed the functional anatomy of the stress response at work in a paradigm, where carp were exposed to a sudden water temperature drop. In carp (and other fish), the endocrine stress axis is already operational in very early life stages, viz., around hatching and comprises hypothalamic, pituitary, and interrenal signaling to adjust the physiology of the hatchling to its dynamically changing environment. Understanding of stress during early life stages is critical as the consequent rises in cortisol may have long lasting effects on survival and fish quality.
...
PMID:CRF and stress in fish. 1640 2

The corticotropin-releasing hormone (CRH) system, consisting of CRH and the homologue neuropeptide urocortin together with their receptors CRH(1) and CRH(2) and a specific binding protein (CRH-BP), holds the main role in mediating the response to stressful stimuli. Besides their expression in the brain, CRH peptides and receptors have been found in multiple peripheral sites. Here we investigate the expression of CRH, urocortin, CRH receptors, and CRH-BP in the wall of human normal and inflamed gallbladders, using RT-PCR and immunohistochemistry. Urocortin, but not CRH gene transcripts, was detected in RNA isolated from human gallbladder biopsy specimens. Urocortin immunoreactivity was localized in epithelial cells of the gallbladder mucosa. Gene expression of CRH(2) receptor was also detected, and the receptor protein had a localization similar to that of urocortin. Finally, CRH-BP gene expression and low levels of protein immunoreactivity were also shown. There were no differences in the expression profiles of all the above molecules between normal and inflamed tissues. In conclusion, the CRH system is present in the human gallbladder, urocortin being the major ligand expressed, possibly exerting an autocrine/paracrine biological role via activation of the CRH(2(alpha)) receptors found locally. Further study is required to enfold the biological role of these effectors in gallbladder physiology and pathogenesis.
...
PMID:Urocortin and corticotropin-releasing hormone receptor type 2 expression in the human gallbladder. 1653 39

Corticotropin-releasing factor (CRF) is a major regulatory peptide in the hypothalamic-pituitary-adrenal (HPA) axis under stress conditions. In response to stress, CRF, produced in the hypothalamic paraventricular nucleus, releases adrenocorticotropic hormone (ACTH) from the anterior pituitary (AP). ACTH in turn stimulates the release of glucocorticoid from the adrenal glands. Glucocorticoid then inhibits hypothalamic production of CRF and pituitary production of ACTH. Mice lacking a functional gene for CRF (CRF KO) showed severe impairment of the HPA axis, indicating that CRF is required for its regulation. We applied oligonucleotide microarray analysis to the AP of CRF KO to identify gene expression induced by CRF. Twenty-four genes showed less than 60% expression in CRF KO compared with normal mice. Real-time PCR analysis revealed that p21-activated kinase 3 (Pak3), prohormone convertase type 1 (PC1), and CRF-binding protein (BP) mRNA expression levels were increased by CRF in AP cells. Both Pak3 and PC1 were also increased by dexamethasone in AP cells, while CRF-BP mRNA levels were reduced. Therefore, both Pak3 and PC1 mRNA levels would be regulated by both CRF and glucocorticoids. Pak3 knockdown inhibited CRF-induced cell viability in AtT-20 cells, suggesting the important role of Pak3 in the proliferation of corticotrophs.
...
PMID:Regulation and role of p21-activated kinase 3 by corticotropin-releasing factor in mouse pituitary. 1894 Feb 5

Bacterial vaginosis (BV) is one of the most prevalent vaginal disorders in adult women and is associated with adverse pregnancy outcomes such as pre-term birth. Genetic factors, particularly in genes involved in inflammation and infection, are associated with this condition. Additionally, environmental risk factors including stress and smoking are associated with BV. The purpose of this study was to identify genetic variants in stress-related genes such as corticotropin-releasing hormone (CRH), receptor 1, receptor 2 and binding protein (CRH-BP) that associate with BV. Also gene-environment effects with smoking are determined. BV was quantified using the Nugent score in 82 white and 65 black women in the first trimester of pregnancy. Associations between Nugent score, genotype and smoking were analyzed using Kruskal-Wallis and Wilcoxon rank sum non-parametric tests. In white women, non-smokers with the CT genotype at CRH-BP + 17487 have lower Nugent scores (median: 0, range: 0-0) than non-smokers with the TT genotype (median: 2, range: 0-8) (P = 0.002); whereas smokers with the CT genotype have higher Nugent scores (median: 6, range: 0-10) than smokers with the TT genotype (median: 1, range: 0-10) (P = 0.021). In black women, the AG genotype at CRH + 3362 or CRH - 1667 is associated with lower Nugent scores (median for both: 3, range: 0-10) compared with the homozygous genotypes (median for each homozygous genotype: 8, range: 0-10). Also, in black women, models remain significant after adjusting for smoking (P = 0.04 for both). These data indicate that susceptibility to BV is affected by patterns of genetic variation in stress-related genes and smoking plays an important role.
...
PMID:Predicting risk of bacterial vaginosis: the role of race, smoking and corticotropin-releasing hormone-related genes. 1913 2

In rainbow trout (Oncorhynchus mykiss) of subordinate social status, circulating cortisol concentrations were elevated under resting conditions but the plasma cortisol and glucose responses to an acute stressor (confinement in a net) were attenuated relative to those of dominant trout. An in vitro head kidney preparation, and analysis of the expression of key genes in the stress axis prior to and following confinement in a net were then used to examine the mechanisms underlying suppression of the acute cortisol stress response in trout experiencing chronic social stress. With porcine adrenocorticotropic hormone (ACTH) as the secretagogue, ACTH-stimulated cortisol production was significantly lower for head kidney preparations from subordinate trout than for those from dominant trout. Dominant and subordinate fish did not, however, differ in the relative mRNA abundance of melanocortin-2 receptor (MC2R), steroidogenic acute regulatory protein (StAR) or cytochrome P450 side chain cleavage enzyme (P450scc) within the head kidney, although the relative mRNA abundance of these genes was significantly higher in both dominant and subordinate fish than in sham trout (trout that did not experience social interactions but were otherwise treated identically to the dominant and subordinate fish). The relative mRNA abundance of all three genes was significantly higher in trout exposed to an acute net stressor than under control conditions. Upstream of cortisol production in the stress axis, plasma ACTH concentrations were not affected by social stress, nor was the relative mRNA abundance of the binding protein for corticotropin releasing factor (CRF-BP). The relative mRNA abundance of CRF in the pre-optic area of subordinate fish was significantly higher than that of dominant or sham fish 1h after exposure to the stressor. Collectively, the results indicate that chronic social stress modulates cortisol production at the level of the interrenal cells, resulting in an attenuated cortisol response to an acute stressor.
...
PMID:Social stress modulates the cortisol response to an acute stressor in rainbow trout (Oncorhynchus mykiss). 2426 85

The hypothalamus-pituitary-interrenal (HPI) axis, involved in the regulation of the neuroendocrine stress responses, presents important players such as corticotropin-releasing hormone (CRH, generally considered as the initiator of this pathway) and CRH-binding protein (CRH-BP, considered as an antagonist of CRH function). CRH and CRH-BP full-length cDNA sequences were obtained from Sparus aurata by screening a brain cDNA library, and their phylogenetic analysis as well as their roles during acute and chronic stress responses were assessed. mRNA expression levels and plasma cortisol concentrations were measured by RT qPCR and ELISA, respectively, in S. aurata juveniles submitted to: i) different environmental salinities in a short-time course response; and ii) food deprivation during 21 days. In addition, osmoregulatory and metabolic parameters in plasma corroborated a clear reorganization depending on the stress source/period. Salinity transfer induced stress as indicated by enhanced plasma cortisol levels, as well as by up-regulated CRH and down-regulated CRH-BP expression values. On the other hand, food deprivation did not affect both expression levels, although plasma cortisol concentrations were enhanced. These results suggest that different stressors are handled through different stress pathways in S. aurata.
...
PMID:Different stressors induce differential responses of the CRH-stress system in the gilthead sea bream (Sparus aurata). 2508 83

Hypersexual Disorder (HD) defined as non-paraphilic sexual desire disorder with components of compulsivity, impulsivity and behavioral addiction, and proposed as a diagnosis in the DSM 5, shares some overlapping features with substance use disorder including common neurotransmitter systems and dysregulated hypothalamic-pituitary-adrenal (HPA) axis function. In this study, comprising 67 HD male patients and 39 male healthy volunteers, we aimed to identify HPA-axis coupled CpG-sites, in which modifications of the epigenetic profile are associated with hypersexuality. The genome-wide methylation pattern was measured in whole blood using the Illumina Infinium Methylation EPIC BeadChip, measuring the methylation state of over 850K CpG sites. Prior to analysis, the global DNA methylation pattern was pre-processed according to standard protocols and adjusted for white blood cell type heterogeneity. We included CpG sites located within 2000bp of the transcriptional start site of the following HPA-axis coupled genes: Corticotropin releasing hormone (CRH), corticotropin releasing hormone binding protein (CRHBP), corticotropin releasing hormone receptor 1 (CRHR1), corticotropin releasing hormone receptor 2 (CRHR2), FKBP5 and the glucocorticoid receptor (NR3C1). We performed multiple linear regression models of methylation M-values to a categorical variable of hypersexuality, adjusting for depression, dexamethasone non-suppression status, Childhood Trauma Questionnaire total score and plasma levels of TNF-alpha and IL-6. Of 76 tested individual CpG sites, four were nominally significant (p<0.05), associated with the genes CRH, CRHR2 and NR3C1. Cg23409074-located 48bp upstream of the transcription start site of the CRH gene - was significantly hypomethylated in hypersexual patients after corrections for multiple testing using the FDR-method. Methylation levels of cg23409074 were positively correlated with gene expression of the CRH gene in an independent cohort of 11 healthy male subjects. The methylation levels at the identified CRH site, cg23409074, were significantly correlated between blood and four different brain regions. CRH is an important integrator of neuroendocrine stress responses in the brain, with a key role in the addiction processes. Our results show epigenetic changes in the CRH gene related to hypersexual disorder in men.
...
PMID:Methylation of HPA axis related genes in men with hypersexual disorder. 2831 50

In teleosts, a complex interaction between several endocrine axes modulates physiological functions related to metabolism, stress, and osmoregulation. Although many studies in fish underline the interconnection between the hypothalamic-pituitary-interrenal (HPI) and hypothalamic-pituitary-thyroid (HPT) endocrine axes, their relationship with the vasotocinergic and isotocinergic systems remains unknown. The aim of the present study is therefore to shed light on the potential cross-regulations between HPT, HPI, and the vasotocinergic and isotocinergic axes in gilthead sea bream (Sparus aurata) at hypothalamic, hypophyseal, and plasma levels. Sea breams were administered with intraperitoneal slow-release implants containing different doses of vasotocin (the active peptide in vasotocinergic system) or cortisol (the last component of HPI axis). Plasma osmolality was higher in active neuropeptides vasotocin (Avt)-treated fish, indicating an osmoregulatory function of this hormone. Low concentrations of Avt increased hypothalamic arginine vasotocin precursor (avt) mRNA levels and increased Avt storage in the pituitary. Avt treatment down-regulated hypothalamic arginine vasotocin receptor v1a-type (avtrv1a), suggesting a negative paracrine co-regulation of the HPI axis due to the close location of avtrv1a and adrenocorticotropin hormone (Acth) cells in the anterior pituitary. Furthermore, the up-regulation observed in arginine vasotocin receptor v2-type (avtrv2) suggests their involvement in metabolic and cortisol-related pathways in the hypothalamus. The decrease in isotocin (It) pituitary storage and the up-regulation of it receptor, observed in the Avt-treated group, reinforce the idea of an interconnection between the vasotocinergic and isotocinergic systems. Cortisol and Avt administration each inhibited the HPI axis, down-regulating crh gene expression in the absence of variations in corticotropin releasing hormone binding protein (crhbp). Finally, both hormonal treatments activated the HPT axis via up-regulation of trh and down-regulation of thrb. Our results provide evidence for strong interactions among the Avt/It, HPI, and HPT axes of marine teleosts, particularly at the hypothalamic level.
...
PMID:Arginine Vasotocin and Cortisol Co-regulate Vasotocinergic, Isotocinergic, Stress, and Thyroid Pathways in the Gilthead Sea Bream (Sparus aurata). 3094 66

1