-
International Journal of Endocrinology 2020-Endorphin, an endogenous opioid peptide, and its -opioid receptor are expressed in brain, liver, and peripheral tissues. -Endorphin induces endothelial dysfunction and...
-Endorphin, an endogenous opioid peptide, and its -opioid receptor are expressed in brain, liver, and peripheral tissues. -Endorphin induces endothelial dysfunction and is related to insulin resistance. We clarified the effects of -endorphin on atherosclerosis. We assessed the effects of -endorphin on the inflammatory response and monocyte adhesion in human umbilical vein endothelial cells (HUVECs), foam cell formation, and the inflammatory phenotype in THP-1 monocyte-derived macrophages, and migration and proliferation of human aortic smooth muscle cells (HASMCs) in vitro. We also assessed the effects of -endorphin on aortic lesions in mice in vivo. The -opioid receptor (OPRM1) was expressed in THP-1 monocytes, macrophages, HASMCs, HUVECs, and human aortic endothelial cells. -Endorphin significantly increased THP-1 monocyte adhesion to HUVECs and induced upregulation of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin via nuclear factor-B (NF-B) and p38 phosphorylation in HUVECs. -Endorphin significantly increased HUVEC proliferation and enhanced oxidized low-density lipoprotein-induced foam cell formation in macrophages. -Endorphin also significantly shifted the macrophage phenotype to proinflammatory M1 rather than anti-inflammatory M2 via NF-B phosphorylation during monocyte-macrophage differentiation and increased migration and apoptosis in association with c-jun-N-terminal kinase, p38, and NF-B phosphorylation in HASMCs. Chronic -endorphin infusion into mice significantly aggravated the development of aortic atherosclerotic lesions, with an increase in vascular inflammation and the intraplaque macrophage/smooth muscle cell ratio, an index of plaque instability. Our study provides the first evidence that -endorphin contributes to the acceleration of the progression and instability of atheromatous plaques. Thus, -opioid receptor antagonists may be useful for the prevention and treatment of atherosclerosis.
PubMed: 32308678
DOI: 10.1155/2020/4139093 -
Journal of Affective Disorders Jan 2021Beta-endorphin (BE) has been suggested to play a central role as to why people engage in NSSI. To our knowledge, no study has systematically assessed this potential...
BACKGROUND
Beta-endorphin (BE) has been suggested to play a central role as to why people engage in NSSI. To our knowledge, no study has systematically assessed this potential relationship in adolescents with NSSI.
METHODS
94 adolescents with NSSI (according to DSM-5 criteria) and 35 healthy controls (HC) were enrolled. All participants received heat pain stimulation, with pain threshold and tolerance measured in °C. Plasma BE levels were assessed. Sociodemographic and clinical characteristics were obtained via semi-structured interviews and self-report questionnaires.
RESULTS
Adolescents with NSSI showed increased pain thresholds (t=2.071, p=.040), lower pain intensity (t==2.122, p=.036) and lower plasma BE levels (t==3.182, p=.002) compared to HC. Groups did not differ on pain tolerance (t=0.911, p=.364). Greater pain threshold correlated positively with borderline personality disorder (BPD) symptoms (r=0.182, p=.039), while pain intensity (r=-0.206, p=.033) and BE levels (r=-0.246, p=.007) correlated negatively with depression severity. No significant relationship was found between pain threshold and plasma BE (r=-0.013, p=.882).
LIMITATIONS
Future studies should implement repeated plasma BE measures to assess BE release in association with pain in NSSI. Validity of plasma BE measures compared to central measures should be considered. Assessing the association between pain sensitivity (PS) and BE in a naturalistic setting presents a promising avenue for future research in NSSI.
CONCLUSIONS
Findings support both reduced PS and basal opioid deficiency as independent biological correlates and potential risk-factors for NSSI. Further longitudinal and experimental studies are needed to investigate the role of BE levels and PS as well as their potential association.
Topics: Adolescent; Borderline Personality Disorder; Humans; Pain; Pain Threshold; Plasma; Self-Injurious Behavior; beta-Endorphin
PubMed: 32961416
DOI: 10.1016/j.jad.2020.09.036 -
Brain Sciences May 2023Microglia are glial cells centrally related to pathophysiology and neuroimmunological regulation of pain through microglia-neuron crosstalk mechanisms. In contrast,... (Review)
Review
Microglia are glial cells centrally related to pathophysiology and neuroimmunological regulation of pain through microglia-neuron crosstalk mechanisms. In contrast, anti-inflammatory mechanisms guided by immunological effectors such as IL-10 trigger the secretion of analgesic substances, culminating in the differential expression of genes encoding endogenous opioid peptides, especially β-endorphin. Thus, when β-endorphin binds to the µ-opioid receptor, it generates neuronal hyperpolarization, inhibiting nociceptive stimuli. This review aimed to summarize the recent advances in understanding the mechanism by which IL-10/β-endorphin can reduce pain. For this, databases were searched for articles from their inception up until November 2022. Two independent reviewers extracted the data and assessed the methodological quality of the included studies, and seventeen studies were considered eligible for this review. Several studies have demonstrated the impact of IL-10/β-endorphin in reducing pain, where IL-10 can stimulate GLP-1R, GRP40, and α7nAChR receptors, as well as intracellular signaling pathways, such as STAT3, resulting in increased β-endorphin expression and secretion. In addition, molecules such as gabapentinoids, thalidomide, cynandione A, morroniside, lemairamin, and cinobufagin, as well as non-pharmacological treatments such as electroacupuncture, reduce pain through IL-10 mediated mechanisms, reflecting a microglia-dependent β-endorphin differential increase. This process represents a cornerstone in pain neuroimmunology knowledge, and the results obtained by different studies about the theme are presented in this review.
PubMed: 37239261
DOI: 10.3390/brainsci13050789 -
Pigment Cell & Melanoma Research Mar 2019Ultraviolet radiation (UVR) has numerous effects on skin, including DNA damage, tanning, vitamin D synthesis, carcinogenesis, and immunomodulation. Keratinocytes... (Review)
Review
Ultraviolet radiation (UVR) has numerous effects on skin, including DNA damage, tanning, vitamin D synthesis, carcinogenesis, and immunomodulation. Keratinocytes containing damaged DNA secrete both α-melanocyte-stimulating hormone (α-MSH), which stimulates pigment production by melanocytes, and the opioid β-endorphin, which can trigger addiction-like responses to UVR. The pigmentation (tanning) response is an adaptation that provides some delayed protection against further DNA damage and carcinogenesis, while the opioid response may be an evolutionary adaptation for promoting sun-seeking behavior to prevent vitamin D deficiency. Here, we review the pigmentation response to UVR, driven by melanocytic microphthalmia-associated transcription factor (MITF), and evidence for UVR-induced melanomagenesis and addiction. We also discuss potential applications of a novel approach to generate protective pigmentation in the absence of UVR (sunless tanning) using a topical small-molecule inhibitor of the salt-inducible kinase (SIK) family.
Topics: Animals; Behavior, Addictive; Humans; Melanins; Microphthalmia-Associated Transcription Factor; Skin; Skin Pigmentation; Ultraviolet Rays
PubMed: 30019545
DOI: 10.1111/pcmr.12726 -
Biology Dec 2022In 1981, Wylie Vale, Joachim Spiess, Catherine Rivier, and Jean Rivier reported on the characterization of a 41-amino-acid peptide from ovine hypothalamic extracts with...
In 1981, Wylie Vale, Joachim Spiess, Catherine Rivier, and Jean Rivier reported on the characterization of a 41-amino-acid peptide from ovine hypothalamic extracts with high potency and intrinsic activity stimulating the secretion of adrenocorticotropic hormone and β-endorphin by cultured anterior pituitary cells. With its sequence known, this neuropeptide was determined to be a hormone and consequently named corticotropin-releasing hormone (CRH), although the term corticotropin-releasing factor (CRF) is still used and preferred in some circumstances. Several decades have passed since this seminal contribution that opened a new research era, expanding the understanding of the coding of stress-related processes. The characterization of CRH receptors, the availability of CRH agonists and antagonists, and advanced immunocytochemical staining techniques have provided evidence that CRH plays a role in the regulation of several biological systems. The purpose of this review is to summarize the present knowledge of this 41-amino-acid peptide.
PubMed: 36552294
DOI: 10.3390/biology11121785 -
Archives of Gynecology and Obstetrics Jul 2018To compare the concentrations of beta endorphin in serum and follicular fluid (FF) of PCOS- and non-PCOS women. Secondarily, to investigate associations between beta...
PURPOSE
To compare the concentrations of beta endorphin in serum and follicular fluid (FF) of PCOS- and non-PCOS women. Secondarily, to investigate associations between beta endorphin and other parameters.
METHODS
Fifty-nine women undergoing in vitro fertilization (IVF) were included in the study. Sixteen were stratified to the PCOS group using the Rotterdam criteria. The remaining 43 women served as controls. Follicular fluid was collected during oocyte retrieval and peripheral blood sampling was performed on the same day. Beta endorphin concentrations in serum and follicular fluid, serum levels of insulin, glucose, LH, estradiol and progesterone were measured. Additionally, testosterone was measured before starting the stimulation protocol.
RESULTS
There was no difference in beta endorphin levels between PCOS- and non-PCOS women. The concentration of the peptide was higher in serum than in FF, likely due to collection of FF after ovulation induction and corresponding to the early luteal phase. We found a significant correlation between the number of mature Metaphase II (MII) oocytes retrieved and beta endorphin concentration in FF. In women with biochemical hyperandrogenemia, beta endorphin levels in FF correlated with testosterone levels.
CONCLUSION
Beta Endorphin concentrations in serum and FF do not differ between PCOS- and non PCOS-women undergoing IVF. However, together with sex hormones, beta endorphin might play a key role in oocyte maturation.
Topics: Adult; Female; Follicular Fluid; Humans; Polycystic Ovary Syndrome; Young Adult; beta-Endorphin
PubMed: 29808249
DOI: 10.1007/s00404-018-4793-6 -
Trends in Endocrinology and Metabolism:... May 2021The steady rise in opioid users and abusers has uncovered multiple detrimental health consequences of perturbed opioid receptor signaling, thereby creating the need to... (Review)
Review
The steady rise in opioid users and abusers has uncovered multiple detrimental health consequences of perturbed opioid receptor signaling, thereby creating the need to better understand the biology of these systems. Among endogenous opioid networks, μ-receptors have received special attention due to their unprecedented biological complexity and broad implications in homeostatic functions. Here, we review the origin, molecular biology, and physiology of endogenous opioids with a special focus on μ-opioid receptor networks within the endocrine system. Moreover, we summarize the current evidence supporting an involvement of the latter in regulating distinct endocrine functions. Finally, we combine these insights to present an integrated perspective on μ-opioid receptor biology and provide an outlook on future studies and unresolved questions in this field.
Topics: Analgesics, Opioid; Endocrine System; Humans; Receptors, Opioid, mu
PubMed: 33676828
DOI: 10.1016/j.tem.2021.02.004 -
International Journal of Molecular... Jan 2018Joint tissues like synovium, articular cartilage, meniscus and subchondral bone, are targets for neuropeptides. Resident cells of these tissues express receptors for... (Review)
Review
Joint tissues like synovium, articular cartilage, meniscus and subchondral bone, are targets for neuropeptides. Resident cells of these tissues express receptors for various neuroendocrine-derived peptides including proopiomelanocortin (POMC)-derived peptides, i.e., α-melanocyte-stimulating hormone (α-MSH), adrenocorticotropin (ACTH) and β-endorphin (β-ED), and sympathetic neuropeptides like vasoactive intestinal peptide (VIP) and neuropeptide y (NPY). Melanocortins attained particular attention due to their immunomodulatory and anti-inflammatory effects in several tissues and organs. In particular, α-MSH, ACTH and specific melanocortin-receptor (MCR) agonists appear to have promising anti-inflammatory actions demonstrated in animal models of experimentally induced arthritis and osteoarthritis (OA). Sympathetic neuropeptides have obtained increasing attention as they have crucial trophic effects that are critical for joint tissue and bone homeostasis. VIP and NPY are implicated in direct and indirect activation of several anabolic signaling pathways in bone and synovial cells. Additionally, pituitary adenylate cyclase-activating polypeptide (PACAP) proved to be chondroprotective and, thus, might be a novel target in OA. Taken together, it appears more and more likely that the anabolic effects of these neuroendocrine peptides or their respective receptor agonists/antagonists may be exploited for the treatment of patients with inflammatory and degenerative joint diseases in the future.
Topics: Animals; Anti-Inflammatory Agents; Bone Density Conservation Agents; Humans; Neuropeptides; Osteoarthritis; Osteogenesis; Receptors, Neuropeptide
PubMed: 29373492
DOI: 10.3390/ijms19020367 -
Medical Science Monitor : International... Sep 2020BACKGROUND Increased levels of endogenous opioids have been observed in patients with schizophrenia; however, the influence of these endogenous opioids on the biology of...
BACKGROUND Increased levels of endogenous opioids have been observed in patients with schizophrenia; however, the influence of these endogenous opioids on the biology of schizophrenia remains unclear. The aim of this study was to evaluate the impact of beta-endorphin (BE) on the course of schizophrenia and risk of relapse. MATERIAL AND METHODS The study included 25 patients hospitalized with schizophrenia and 47 controls. Their symptoms were evaluated using Positive and Negative Syndrome Scale (PANSS) and composite index at five points: at the onset of hospitalization; after 4, 6 and 10 weeks of treatment; and after 12 months. ß-endorphin plasma concentrations were assessed in patients at study enrollment and after 6 weeks of treatment. Data regarding rehospitalization during follow-up were also collected. RESULTS Patients had higher BE concentration than controls at study enrollment (P=0.002) and after 6 weeks (P=0.000). BE levels increased during treatment (mean 0.538ng/mL vs. mean 0.624 ng/mL; P=0.007). No correlation was found between BE concentration and PANSS subscale score at any stage of the study. A higher BE level at study enrollment was related to a predominance of negative symptoms after 1 year, measured with composite index (R=-0.404; P=0.045). Patients who were later hospitalized again were significantly more likely to demonstrate an increase in BE levels over 6 weeks (P=0.001). CONCLUSIONS Individuals with schizophrenia demonstrated higher BE concentrations than healthy controls; this tendency was particularly apparent in those affected by negative symptoms. The imbalance in the endogenous opioid system might adversely alter the course of disease and predispose patients to persistence of negative symptoms, despite antipsychotic treatment.
Topics: Adult; Antipsychotic Agents; Female; Follow-Up Studies; Humans; Male; Middle Aged; Recurrence; Schizophrenia; Treatment Outcome; beta-Endorphin
PubMed: 32892205
DOI: 10.12659/MSM.924307 -
International Journal of Molecular... Apr 2021There exist three main types of endogenous opioid peptides, enkephalins, dynorphins and β-endorphin, all of which are derived from their precursors. These endogenous... (Review)
Review
There exist three main types of endogenous opioid peptides, enkephalins, dynorphins and β-endorphin, all of which are derived from their precursors. These endogenous opioid peptides act through opioid receptors, including mu opioid receptor (MOR), delta opioid receptor (DOR) and kappa opioid receptor (KOR), and play important roles not only in analgesia, but also many other biological processes such as reward, stress response, feeding and emotion. The MOR gene, OPRM1, undergoes extensive alternative pre-mRNA splicing, generating multiple splice variants or isoforms. One type of these splice variants, the full-length 7 transmembrane (TM) Carboxyl ()-terminal variants, has the same receptor structures but contains different intracellular -terminal tails. The pharmacological functions of several endogenous opioid peptides through the mouse, rat and human OPRM1 7TM -terminal variants have been considerably investigated together with various mu opioid ligands. The current review focuses on the studies of these endogenous opioid peptides and summarizes the results from early pharmacological studies, including receptor binding affinity and G protein activation, and recent studies of β-arrestin2 recruitment and biased signaling, aiming to provide new insights into the mechanisms and functions of endogenous opioid peptides, which are mediated through the OPRM1 7TM -terminal splice variants.
Topics: Alternative Splicing; Animals; Humans; Opioid Peptides; Protein Isoforms; RNA Precursors; Receptors, Opioid, mu
PubMed: 33917474
DOI: 10.3390/ijms22073779