-
Addiction Biology May 2019Binge drinking is an increasingly common pattern of risky use associated with numerous health problems, including alcohol use disorders. Because low basal plasma levels...
Binge drinking is an increasingly common pattern of risky use associated with numerous health problems, including alcohol use disorders. Because low basal plasma levels of β-endorphin (β-E) and an increased β-E response to alcohol are evident in genetically at-risk human populations, this peptide is thought to contribute to the susceptibility for disordered drinking. Animal models suggest that the effect of β-E on consumption may be sex-dependent. Here, we studied binge-like EtOH consumption in transgenic mice possessing varying levels of β-E: wild-type controls with 100% of the peptide (β-E +/+), heterozygous mice constitutively modified to possess 50% of wild-type levels (β-E +/-) and mice entirely lacking the capacity to synthesize β-E (-/-). These three genotypes and both sexes were evaluated in a 4-day, two-bottle choice, drinking in the dark paradigm with limited access to 20% EtOH. β-E deficiency determined sexually divergent patterns of drinking in that β-E -/- female mice drank more than their wild-type counterparts, an effect not observed in male mice. β-E -/- female mice also displayed elevated basal anxiety, plasma corticosterone and corticotropin-releasing hormone mRNA in the extended amygdala, and all of these were normalized by EtOH self-administration. These data suggest that a heightened risk for excessive EtOH consumption in female mice is related to the drug's ability to ameliorate an overactive anxiety/stress-like state. Taken together, our study highlights a critical impact of sex on neuropeptide regulation of EtOH consumption.
Topics: Animals; Binge Drinking; Central Nervous System Depressants; Corticosterone; Corticotropin-Releasing Hormone; Ethanol; Female; Heterozygote; Male; Mice, Transgenic; Models, Animal; Sex Characteristics; beta-Endorphin
PubMed: 29424043
DOI: 10.1111/adb.12610 -
ENeuro 2021Naltrexone is an opioid receptor antagonist approved for the treatment of alcohol and opioid use disorders at doses of 50-150 mg/d. Naltrexone has also been prescribed...
Naltrexone is an opioid receptor antagonist approved for the treatment of alcohol and opioid use disorders at doses of 50-150 mg/d. Naltrexone has also been prescribed at much lower doses (3-6 mg/d) for the off-label treatment of inflammation and pain. Currently, a compelling mechanistic explanation for the reported efficacy of low-dose naltrexone (LDN) is lacking and none of the proposed mechanisms can explain patient reports of improved mood and sense of well-being. Here, we examined the possibility that LDN might alter the activity of the endogenous opioid system involving proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARH) in male and female mice. Known actions of POMC neurons could account for changes in pain perception and mood. However, using electrophysiologic, imaging and peptide measurement approaches, we found no evidence for such a mechanism. LDN did not change the sensitivity of opioid receptors regulating POMC neurons, the production of the β-endorphin precursor mRNA, nor the release of β-endorphin into plasma. Spontaneous postsynaptic currents (sPSCs) onto POMC neurons were slightly decreased after LDN treatment and GCaMP fluorescent signal, a proxy for intracellular calcium levels, was slightly increased. However, LDN treatment did not appear to change POMC neuron firing rate, resting membrane potential, nor action potential threshold. Therefore, LDN appears to have only slight effects on POMC neurons that do not translate to changes in intrinsic excitability or baseline electrical activity and mechanisms beyond POMC neurons and altered opioid receptor sensitivity should continue to be explored.
Topics: Analgesics, Opioid; Animals; Female; Humans; Male; Mice; Naltrexone; Neurons; Pro-Opiomelanocortin; beta-Endorphin
PubMed: 34031099
DOI: 10.1523/ENEURO.0087-21.2021 -
JPMA. the Journal of the Pakistan... Apr 2023The purpose of this study was to investigate whether serum β-endorpin and neuropeptide Y were associated with changes in levels of thyroid hormones in children...
The purpose of this study was to investigate whether serum β-endorpin and neuropeptide Y were associated with changes in levels of thyroid hormones in children suffering from anorexia. One hundred and five anorexic children admitted to Xianning City Central Hospital, China, from August 2019 to July 2021, were selected as case group, while 105 normal children were selected as normal control group. Serum β-endorpin and neuropeptide Y levels in the case group were lower than those in the normal control group (both p<0.001), and serum triiodothyronine and thyroxine levels were also lower (both p<0.001). Serum β-endorpin and neuropeptide Y levels in the case group were positively correlated with triiodothyronine and thyroxine. There is a reduced level of serum β-endorpin, neuropeptide Y, and thyroid hormones in anorexic children, and it is possible that they are connected and work together in regulating ingestion.
Topics: Child; Humans; Anorexia; Neuropeptide Y; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine; beta-Endorphin
PubMed: 37052007
DOI: 10.47391/JPMA.6616 -
Redox Biology Sep 2020The prevalence of chronic widespread pain (CWP) in people with HIV is high, yet the underlying mechanisms are elusive. Leukocytes synthesize the endogenous opioid,...
The prevalence of chronic widespread pain (CWP) in people with HIV is high, yet the underlying mechanisms are elusive. Leukocytes synthesize the endogenous opioid, β-endorphin, within their endoplasmic reticulum (ER). When released into plasma, β-endorphin dampens nociception by binding to opioid receptors on sensory neurons. We hypothesized that the heme-dependent redox signaling induces ER stress, which attenuates leukocyte β-endorphins levels/release, thereby increasing pain sensitivity in people with HIV. Results demonstrated that HIV positive individuals with CWP had increased plasma methemoglobin, erythrocytes membrane oxidation, hemolysis, and low plasma heme scavenging enzyme, hemopexin, compared to people with HIV without CWP and HIV-negative individuals with or without pain. In addition, the leukocytes from people with HIV with CWP had attenuated levels of the heme metabolizing enzyme, heme oxygenase-1, which metabolizes free heme to carbon-monoxide and biliverdin. These individuals also had elevated ER stress, and low β-endorphin in leukocytes. In vitro, heme exposure or heme oxygenase-1 deletion, decreased β-endorphins in murine monocytes/macrophages. Treating cells with a carbon-monoxide donor or an ER stress inhibitor, increased β-endorphins. To mimic hemolytic effects in a preclinical model, C57BL/6 mice were injected with phenylhydrazine hydrochloride (PHZ). PHZ increased cell-free heme and ER stress, decreased leukocyte β-endorphin levels and hindpaw mechanical sensitivity thresholds. Treatment of PHZ-injected mice with hemopexin blocked these effects, suggesting that heme-induced ER stress and a subsequent decrease in leukocyte β-endorphin is responsible for hypersensitivity in people with HIV.
Topics: Animals; HIV Infections; Heme; Leukocytes; Mice; Mice, Inbred C57BL; Pain; beta-Endorphin
PubMed: 32828015
DOI: 10.1016/j.redox.2020.101684 -
General Pharmacology 19891. The purpose of this study was to determine the plasma levels of beta-endorphin (beta-END) and ACTH in the perioperative period, define correlations of hormonal plasma...
1. The purpose of this study was to determine the plasma levels of beta-endorphin (beta-END) and ACTH in the perioperative period, define correlations of hormonal plasma levels with clinical parameters and establish the effect of droperidol premedication on hormonal levels and clinical parameters. 2. Twenty two were assigned to one of two groups: (1) Control (no premedication) and (2) droperidol (7.5 mg im) premedication. 3. Venous blood samples and clinical evaluations were done the day prior to surgery, just prior to induction of anesthesia and 1-1.5 hr postoperatively. 4. The results indicate that (1) expectancy of surgery on arrival to the operating room increases beta-END but not ACTH plasma levels, (2) this increase in beta-END is not affected by droperidol administration and (3) postsurgical stress increases beta-END and ACTH above operating room levels. 5. These results indicate that although beta-END and ACTH are both produced by the pituitary and derived from a common precursor, the type of stimuli (pre- versus postsurgical stress) seems to differentially affect their plasma levels.
Topics: Adrenocorticotropic Hormone; Adult; Blood Pressure; Droperidol; Heart Rate; Humans; Intraoperative Period; Male; Preanesthetic Medication; Radioimmunoassay; Surgical Procedures, Operative; beta-Endorphin
PubMed: 2546852
DOI: 10.1016/0306-3623(89)90185-7 -
International Journal of Molecular... Dec 2022The opioid peptide β-endorphin coexists in the pituitary and brain in its -acetylated form, which does not bind to opioid receptors. We now report that these...
The opioid peptide β-endorphin coexists in the pituitary and brain in its -acetylated form, which does not bind to opioid receptors. We now report that these neuropeptides exhibited opposite effects in in vivo paradigms, in which ligands of the sigma type 1 receptor (σ1R) displayed positive effects. Thus, -acetyl β-Endorphin reduced vascular infarct caused by permanent unilateral middle cerebral artery occlusion and diminished the incidence of -methyl-D-aspartate acid-promoted convulsive syndrome and mechanical allodynia caused by unilateral chronic constriction of the sciatic nerve. Moreover, -acetyl β-Endorphin reduced the analgesia of morphine, β-Endorphin and clonidine but enhanced that of DAMGO. All these effects were counteracted by β-Endorphin and absent in σ1R mice. We observed that σ1Rs negatively regulate mu-opioid receptor (MOR)-mediated morphine analgesia by binding and sequestering G proteins. In this scenario, β-Endorphin promoted the exchange of σ2Rs by G proteins at σ1R oligomers and increased the regulation of G proteins by MORs. The opposite was observed for the -acetyl derivative, as σ1R oligomerization decreased and σ2R binding was favored, which displaced G proteins; thus, MOR-regulated transduction was reduced. Our findings suggest that the pharmacological β-Endorphin-specific epsilon receptor is a σ1R-regulated MOR and that β-Endorphin and -acetyl β-Endorphin are endogenous ligands of σ1R.
Topics: Animals; Mice; beta-Endorphin; GTP-Binding Proteins; Ligands; Morphine; Pain; Receptors, Opioid; Receptors, Opioid, mu; Receptors, sigma
PubMed: 36614024
DOI: 10.3390/ijms24010582 -
International Journal of Environmental... Aug 2022The aim of this study was to evaluate the influence of β-endorphins and serotonin on the course of treatment, disease-free time, and overall survival of patients with...
The aim of this study was to evaluate the influence of β-endorphins and serotonin on the course of treatment, disease-free time, and overall survival of patients with ovarian cancer. This study may contribute to the identification of modifiable factors that may influence the treatment of ovarian cancer. The research was carried out in a group of 162 patients of which 139 respondents were included in the research; ovarian cancer was diagnosed in 78 of these patients. The study consisted of three stages. In the first stage of diagnostics, a survey among the patients was carried out. In the second stage-5 mL of blood was collected from each patient ( = 139) in the preoperative period to determine the concentration of β-endorphin and serotonin. In the third stage-blood samples were collected from those patients who had completed chemotherapy treatment or had surgery. Concentrations of β-endorphin and serotonin were measured by the Luminex method, using the commercial Luminex Human Discovery Assay kit. The average age of the patients was 62.99 years. The level of β-endorphin significantly differs among patients diagnosed with ovarian cancer and among patients in the control group (202.86; SD-15.78 vs. 302.00; SD-24.49). A lower level of β-endorphins was found in the patients with a recurrence of the neoplastic process compared to those without recurrence (178.84; SD-12.98 vs. 205.66; SD-13.37). On the other hand, the level of serotonin before chemotherapy was higher in the group of people with disease recurrence compared to those without recurrence (141.53; SD-15.33 vs. 134.99; SD-10.08). Statistically significantly positive correlations were found between the level of β-endorphin and both disease-free time (β-endorphin levels before chemotherapy: rho Spearman 0.379, < 0.027; β-endorphin levels after chemotherapy: rho Spearman 0.734 < 0.001) and survival time (β-endorphin levels before chemotherapy: rho Spearman 0.267, < 0.018; β-endorphin levels after chemotherapy: rho Spearman 0.654 < 0.001). 1. The levels of serotonin and β-endorphin levels are significantly related to ovarian cancer and change during treatment. 2. High mean preoperative concentrations of β-endorphins were significantly related to overall survival and disease-free time.
Topics: Biological Factors; Endorphins; Female; Humans; Middle Aged; Ovarian Neoplasms; Serotonin; beta-Endorphin
PubMed: 36078233
DOI: 10.3390/ijerph191710516 -
Endocrine Reviews Aug 2012Proopiomelanocortin (POMC)-derived peptides such as melanocortins and β-endorphin (β-ED) exert their pleiotropic effects via binding to melanocortin receptors (MCR)... (Review)
Review
Proopiomelanocortin (POMC)-derived peptides such as melanocortins and β-endorphin (β-ED) exert their pleiotropic effects via binding to melanocortin receptors (MCR) and opioid receptors (OR). There is now compelling evidence for the existence of a functional POMC system within the osteoarticular system. Accordingly, distinct cell types of the synovial tissue and bone have been identified to generate POMC-derived peptides like β-ED, ACTH, or α-MSH. MCR subtypes, especially MC1R, MC2R (the ACTH receptor), MC3R, and MC4R, but also the μ-OR and δ-OR, have been detected in various cells of the synovium, cartilage, and bone. The respective ligands of these POMC-derived peptide receptors mediate an increasing number of newly recognized biological effects in the osteoarticular system. These include bone mineralization and longitudinal growth, cell proliferation and differentiation, extracellular matrix synthesis, osteoprotection, and immunomodulation. Importantly, bone formation is also regulated by the central melanocortin system via a complex hormonal interplay with other organs and tissues involved in energy metabolism. Among the POMC-derived peptides examined in cell culture systems from osteoarticular tissue and in animal models of experimentally induced arthritis, α-MSH, ACTH, and MC3R-specific agonists appear to have the most promising antiinflammatory actions. The effects of these melanocortin peptides may be exploited in future for the treatment of patients with inflammatory and degenerative joint diseases.
Topics: Animals; Arthritis, Rheumatoid; Bone and Bones; Cartilage; Humans; Joints; Melanocortins; Osteoarthritis; Pro-Opiomelanocortin; Signal Transduction; beta-Endorphin
PubMed: 22736674
DOI: 10.1210/er.2011-1016 -
Asian Journal of Andrology Nov 2006To access beta-endorphin levels in serum as well as seminal plasma in different infertile male groups.
AIM
To access beta-endorphin levels in serum as well as seminal plasma in different infertile male groups.
METHODS
Beta-endorphin was estimated in the serum and seminal plasma by enzyme-linked immunosorbent assay (ELISA) method in 80 infertile men equally divided into four groups: non-obstructive azoospermia (NOA), obstructive azoospermia (OA), congenital bilateral absent vas deferens (CBVAD) and asthenozoospermia. The results were compared to those of 20 normozoospermic proven fertile men.
RESULTS
There was a decrease in the mean levels of beta-endorphin in the seminal plasma of all successive infertile groups (mean +/- SD: NOA 51.30 +/- 27.37, OA 51.88 +/- 9.47, CBAVD 20.36 +/- 13.39, asthenozoospermia 49.26 +/- 12.49 pg/mL, respectively) compared to the normozoospermic fertile control (87.23 +/- 29.55 pg/mL). This relation was not present in mean serum level of beta-endorphin between four infertile groups (51.09 +/- 14.71, 49.76 +/- 12.4, 33.96 +/- 7.2, 69.1 +/- 16.57 pg/mL, respectively) and the fertile control group (49.26 +/- 31.32 pg/mL). The CBVAD group showed the lowest seminal plasma mean level of beta-endorphin. Testicular contribution of seminal beta-endorphin was estimated to be approximately 40%. Seminal beta-endorphin showed significant correlation with the sperm concentration (r = 0.699, P = 0.0188) and nonsignificant correlation with its serum level (r = 0.375, P = 0.185) or with the sperm motility percentage (r = 0.470, P = 0.899).
CONCLUSION
The estimation of beta-endorphin alone is not conclusive to evaluate male reproduction as there are many other opiates acting at the hypothalamic pituitary gonadal axis.
Topics: Asthenozoospermia; Azoospermia; Enzyme-Linked Immunosorbent Assay; Humans; Infertility, Male; Male; Prospective Studies; Semen; Vas Deferens; beta-Endorphin
PubMed: 16751995
DOI: 10.1111/j.1745-7262.2006.00180.x -
CNS Neuroscience & Therapeutics Dec 2018The odor identification ability and its hedonic judgment in patients with schizophrenia were evaluated in the study. The association between olfactory performance and...
AIMS
The odor identification ability and its hedonic judgment in patients with schizophrenia were evaluated in the study. The association between olfactory performance and negative symptoms and β-endorphin concentration was also analyzed.
METHODS
Study groups consisted of 23 patients with negative symptoms (PN) and 25 without predominant negative symptoms (PP) and 21 healthy individuals. The University of Pennsylvania Smell Identification Test, odor hedonic evaluation, and plasma concentrations of β-endorphin assay in all participants were performed.
RESULTS
PN perceived the poorer olfactory identification; nevertheless, they evaluated unpleasant odors as more pleasant than PP and controls. Beta-endorphin concentration was significantly higher among PN than in other study groups. No association was observed between β-endorphin and odors identification and odor hedonic judgment among all study groups.
CONCLUSIONS
There is potential relationship between increased β-endorphin concentration and severity of negative symptoms. Patients with predominant negative symptoms tend to evaluate odors as significantly more pleasant. Individuals with this subtype of schizophrenia might present specific, altered pattern of smell identification and hedonic judgment. Presumably, β-endorphin has no direct influence on olfactory identification performance and hedonic judgment in schizophrenia.
Topics: Adult; Female; Humans; Judgment; Male; Middle Aged; Odorants; Olfaction Disorders; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Young Adult; beta-Endorphin
PubMed: 29638031
DOI: 10.1111/cns.12849