Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Approximately 10% of pregnant women are at risk of preterm delivery and receive synthetic glucocorticoids (sGC) to promote fetal lung development. Studies have indicated that prenatal sGC therapy modifies hypothalamic-pituitary-adrenal (HPA) function in first-generation (F(1)) offspring. The objective of this study was to determine whether differences in HPA function and behavior are evident in the subsequent (F(2)) generation. Pregnant guinea pigs (F(0)) received betamethasone (BETA; 1 mg/kg) or saline on gestational d 40/41, 50/51, and 60/61. F(1) females were mated with control males to create F(2) offspring. HPA function was assessed in juvenile and adult F(2) offspring. Locomotor activity was assessed in juvenile offspring. Analysis of HPA-related gene expression was undertaken in adult hippocampi, hypothalami, and pituitaries. Locomotor activity was reduced in F(2) BETA males (P < 0.05). F(2) BETA offspring displayed blunted cortisol response to swim stress (P < 0.05). After dexamethasone challenge, F(2) BETA males and females displayed increased and decreased negative feedback, respectively. F(2) BETA females had reduced pituitary levels of proopiomelanocortin (and adrenocorticotropic hormone), and corticotropin-releasing hormone receptor mRNA and protein (P < 0.05). F(2) BETA males displayed increased hippocampal glucocorticoid receptor (P < 0.001), whereas in BETA females, hippocampal glucocorticoid receptor and mineralocorticoid receptor mRNA were decreased (P < 0.05). In conclusion, prenatal BETA treatment affects HPA function and behavior in F(2) offspring. In F(2) BETA females, pituitary function appears to be primarily affected, whereas hippocampal glucocorticoid feedback systems appear altered in both F(2) BETA males and females. These data have clinical implication given the widespread use of repeat course glucocorticoid therapy in the management of preterm labour.
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PMID:Transgenerational effects of prenatal synthetic glucocorticoids on hypothalamic-pituitary-adrenal function. 2256 76

Accumulating research suggests a moderating role for the corticotropin-releasing hormone receptor 1 gene (CRHR1) in the association between childhood adversity and adult depression. The present study aims to replicate recent findings using different genetic variants and measures of early adversity assessed both prospectively and retrospectively. Data were collected in the context of an ongoing epidemiological cohort study following the outcome of early risk factors from birth into adulthood. 300 participants (137 males, 163 females) were genotyped for four CRHR1 SNPs (rs7209436, rs110402, rs242924, and rs17689882) and completed the Beck Depression Inventory at ages 19, 22 and 23 years. Childhood adversity was assessed using the Childhood Trauma Questionnaire and by a standardized parent interview yielding an index of family adversity. Our results indicate that CRHR1 and childhood adversity interacted to predict depressive symptoms in young adults. Specifically, we found that the impact of childhood maltreatment on adult depressive symptoms was significantly higher in individuals (i) with two copies of the CRHR1 TAT haplotype, and (ii) homozygous for the G allele of rs17689882. The interaction was demonstrated for exposure to childhood maltreatment as assessed by retrospective self-report, but not to prospectively ascertain objective family adversity. The present study partially replicates recent findings of a CRHR1 by childhood adversity interaction with regard to adult depression highlighting the subjective characteristics of the environmental pathogen that is operative in this interaction.
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PMID:Interactive effects of corticotropin-releasing hormone receptor 1 gene and childhood adversity on depressive symptoms in young adults: findings from a longitudinal study. 2274 21

Patients with 17q21.31 microdeletions frequently have neurologic abnormalities, especially seizures. This report is of a child with a deletion in this location who developed infantile spasms, a seizure type not specifically described in this syndrome. FISH analysis of parental blood metaphases demonstrated that the deletions occurred de novo. The deleted region encompasses the previously defined critical region for the 17q21.31 microdeletion syndrome, and includes the gene encoding for corticotropin-releasing hormone receptor 1, a protein implicated in hyperexcitability, and potentially in infantile spasms. Treatment with ACTH led to spasm cessation, consistent with its expected repression of CRH levels, which should be augmented by CRHR1 deletion, although this response was transient.
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PMID:17q21.31 microdeletion associated with infantile spasms. 2312 21

We previously reported that gestational intermittent hypoxia (GIH) causes anxiety-like behavior in neonatal rats. Here, we showed that the anxiogenic effect was correlated with upregulation of corticotropin-releasing hormone receptor 1 (CRHR1) in the hypothalamic paraventricular nuclei (PVN) by GIH, and was selective to male offspring. The anxiety-like behavior was assessed by both the open field (OF) and elevated plus maze (EPM) tests. We demonstrated that GIH triggered anxiety-like behavior in male offspring, but not in female offspring or in the postpartum dams. Microinjection of antalarmin, a CRHR1-selective antagonist, into the PVN of the male offspring significantly increased the distance traveled and time spent in the central portion of the OF, and the time spent in the open arms in the EPM compared with controls. However, microinjection of the CRHR2 agonist, urocortin III, into the PVN did not affect anxiogenic behavior in the male offspring. These findings clearly demonstrate a gender-selective effect of GIH to increase anxiety-like behavior and this anxiogenic effect might be linked to embryogenically-driven upregulation of PVN CRHR1.
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PMID:Upregulation of PVN CRHR1 by gestational intermittent hypoxia selectively triggers a male-specific anxiogenic effect in rat offspring. 2316 43

Alternative mRNA splicing as an important mechanism for generating protein diversity has been implicated to affect 60-70% of human genes (Wang et al., 2008). The G protein-coupled receptors (GPCRs), the largest group of membrane receptors, have a broad distribution and function. Posttranslational modifications or/and association with regulatory proteins can govern cell- and tissue-specific pharmacological, signaling, and regulatory characteristics of GPCRs. However, increasing body of evidence suggests that alternative splicing of GPCRs is a mechanism that can modulate GPCRs' function (Einstein et al., 2008). Many GPCRs have a potential to undergo alternative pre-mRNA splicing (~50%). Due to a general lack of isoform-specific antibodies, GPCRs' alternative splicing is mainly studied on mRNA level employing various PCR techniques. Functional characteristics (including signaling and structure) of alternatively spliced GPCRs are studied in overexpression system employing standard biochemical techniques. In this chapter, we will describe the methods for detection and quantification of alternatively spliced GPCR mRNA. As the experimental paradigm, we use type 1 corticotropin-releasing hormone receptor (CRH-R1).
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PMID:Alternative mRNA splicing of G protein-coupled receptors. 2333 7

The cortisol response to psychosocial stress may become dysregulated in stress-related disorders. It is potentiated by pituitary secretion of adrenocorticotropic hormone (ACTH), which is, in part, regulated by arginine vasopressin receptor-1B (AVPR1B). AVPR1B variants were previously reported to associate with mood and anxiety disorders. This study aims, for the first time, to investigate association of AVPR1B genetic variants with mood and anxiety outcomes in suicidal behavior.Using a family-based study design of 660 complete nuclear family trios with offspring who have made a suicide attempt (SA), we tested the direct association and linkage of AVPR1B single nucleotide polymorphisms (SNPs) with SA, as well as with depression and anxiety in SA. Main findings were the association and linkage of AVPR1B exon 1 SNP rs33990840 and a major 6-SNP haplotype representative of all common AVPR1B-SNPs, on the outcome of high Beck Depression Inventory scores in SA. By contrast, genetic associations with lifetime diagnoses of depression and anxiety in SA or gene-environment interactions between AVPR1B variants and stressful life events (SLEs) were not significant. An exploratory screen of interactions between AVPR1B and CRHR1 (corticotropin-releasing hormone receptor-1), the principal pituitary regulator of ACTH secretion, showed no support for gene-gene interactions on the studied outcomes. The results suggest that AVPR1B genetic variation, eg, non-synonymous SNP rs33990840 mediating putative consequences on ligand binding, has a role in SA etiology characterized by elevated depression symptoms, without involving AVPR1B-moderation of SLEs.
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PMID:Family-based study of AVPR1B association and interaction with stressful life events on depression and anxiety in suicide attempts. 2342 93

Major depressive disorder (MDD) is a long-term, recurrent condition that often takes a chronic course. It seems imperative that research should be focused on gaining a better understanding of what predicts recurrent MDD. As a major mediator of the stress response, corticotropin-releasing-hormone receptor 1 (CRHR1) has been demonstrated to be an important contributor to the pathogenesis of MDD. In this study, we show a significant increase in the G-allele (rs242939) of the CRHR1 gene in the recurrent MDD group compared with the control group, and an overrepresentation of G-G-T hyplotype of the CRHR1 gene in recurrent MDD. We also demonstrate the interaction of the CRHR1 gene and negative life events in recurrent MDD. These results suggest that the CRHR1 gene could modify the susceptibility to developing recurrent MDD following negative life events in adulthood.
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PMID:Negative life events and corticotropin-releasing-hormone receptor1 gene in recurrent major depressive disorder. 2352 11

Stress impairs cognition via corticotropin-releasing hormone receptor 1 (CRHR1), but the molecular link between abnormal CRHR1 signaling and stress-induced cognitive impairments remains unclear. We investigated whether the cell adhesion molecule nectin-3 is required for the effects of CRHR1 on cognition and structural remodeling after early-life stress exposure. Postnatally stressed adult mice had decreased hippocampal nectin-3 levels, which could be attenuated by CRHR1 inactivation and mimicked by corticotropin-releasing hormone (CRH) overexpression in forebrain neurons. Acute stress dynamically reduced hippocampal nectin-3 levels, which involved CRH-CRHR1, but not glucocorticoid receptor, signaling. Suppression of hippocampal nectin-3 caused spatial memory deficits and dendritic spine loss, whereas enhancing hippocampal nectin-3 expression rescued the detrimental effects of early-life stress on memory and spine density in adulthood. Our findings suggest that hippocampal nectin-3 is necessary for the effects of stress on memory and structural plasticity and indicate that the CRH-CRHR1 system interacts with the nectin-afadin complex to mediate such effects.
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PMID:Nectin-3 links CRHR1 signaling to stress-induced memory deficits and spine loss. 2364 83

The ability to identify predictors of aversive events allows organisms to appropriately respond to these events, and failure to acquire these fear contingencies can lead to maladaptive contextual anxiety. Recently, preclinical studies demonstrated that the corticotropin-releasing factor and serotonin systems are interactively involved in adaptive fear acquisition. Here, 150 healthy medication-free human subjects completed a cue and context fear conditioning procedure in a virtual reality environment. Fear potentiation of the eyeblink startle reflex (FPS) was measured to assess both uninstructed fear acquisition and instructed fear expression. All participants were genotyped for polymorphisms located within regulatory regions of the corticotropin releasing hormone receptor 1 (CRHR1 - rs878886) and the serotonin transporter (5HTTLPR). These polymorphisms have previously been linked to panic disorder and anxious symptomology and personality, respectively. G-allele carriers of CRHR1 (rs878886) showed no acquisition of fear conditioned responses (FPS) to the threat cue in the uninstructed phase, whereas fear acquisition was present in C/C homozygotes. Moreover, carrying the risk alleles of both rs878886 (G-allele) and 5HTTLPR (short allele) was associated with increased FPS to the threat context during this phase. After explicit instructions regarding the threat contingency were given, the cue FPS and context FPS normalized in all genotype groups. The present results indicate that genetic variability in the corticotropin-releasing hormone receptor 1, especially in interaction with the 5HTTLPR, is involved in the acquisition of fear in humans. This translates prior animal findings to the human realm.
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PMID:Human fear acquisition deficits in relation to genetic variants of the corticotropin releasing hormone receptor 1 and the serotonin transporter. 2371 80

Previous studies have reported that the hypothalamic-pituitary-adrenal axis is involved with personality traits. We examined the association between corticotropin-releasing hormone receptor (CRHR) genes and personality traits. We investigated the 12 single-nucleotide polymorphisms of intron CRHR (six in CRHR1 and six in CRHR2, respectively) in 218 healthy volunteers using TaqMan PCR assays. Personality traits were assessed using the Revised NEO-Personality Inventory, the Temperament and Character Inventory, and the State-Trait Anxiety Inventory. No significant associations were observed between CRHR1 and CRHR2 expression and personality traits. These results fail to provide support for an association of CRHR1 and CRHR2 with personality traits in a Japanese adult population.
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PMID:Association between corticotropin-releasing hormone receptor 1 and 2 (CRHR1 and CRHR2) gene polymorphisms and personality traits. 2398 82


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