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American Journal of Obstetrics and... Mar 2024Oxytocin is a reproductive hormone implicated in the process of parturition and widely used during labor. Oxytocin is produced within the supraoptic nucleus and... (Review)
Review
Oxytocin is a reproductive hormone implicated in the process of parturition and widely used during labor. Oxytocin is produced within the supraoptic nucleus and paraventricular nucleus of the hypothalamus and released from the posterior pituitary lobe into the circulation. Oxytocin is released in pulses with increasing frequency and amplitude in the first and second stages of labor, with a few pulses released in the third stage of labor. During labor, the fetus exerts pressure on the cervix of the uterus, which activates a feedforward reflex-the Ferguson reflex-which releases oxytocin. When myometrial contractions activate sympathetic nerves, it decreases oxytocin release. When oxytocin binds to specific myometrial oxytocin receptors, it induces myometrial contractions. High levels of circulating estrogen at term make the receptors more sensitive. In addition, oxytocin stimulates prostaglandin synthesis and release in the decidua and chorioamniotic membranes by activating a specific type of oxytocin receptor. Prostaglandins contribute to cervical ripening and uterine contractility in labor. The oxytocin system in the brain has been implicated in decreasing maternal levels of fear, pain, and stress, and oxytocin release and function during labor are stimulated by a social support. Moreover, studies suggest, but have not yet proven, that labor may be associated with long-term, behavioral and physiological adaptations in the mother and infant, possibly involving epigenetic modulation of oxytocin production and release and the oxytocin receptor. In addition, infusions of synthetic oxytocin are used to induce and augment labor. Oxytocin may be administered according to different dose regimens at increasing rates from 1 to 3 mIU/min to a maximal rate of 36 mIU/min at 15- to 40-minute intervals. The total amount of synthetic oxytocin given during labor can be 5 to 10 IU, but lower and higher amounts of oxytocin may also be given. High-dose infusions of oxytocin may shorten the duration of labor by up to 2 hours compared with no infusion of oxytocin; however, it does not lower the frequency of cesarean delivery. When synthetic oxytocin is administered, the plasma concentration of oxytocin increases in a dose-dependent way: at infusion rates of 20 to 30 mIU/min, plasma oxytocin concentration increases approximately 2- to 3-fold above the basal level. Synthetic oxytocin administered at recommended dose levels is not likely to cross the placenta or maternal blood-brain barrier. Synthetic oxytocin should be administered with caution as high levels may induce tachystole and uterine overstimulation, with potentially negative consequences for the fetus and possibly the mother. Of note, 5 to 10 IU of synthetic oxytocin is often routinely given as an intravenous or intramuscular bolus administration after delivery to induce uterine contractility, which, in turn, induces uterine separation of the placenta and prevents postpartum hemorrhage. Furthermore, it promotes the expulsion of the placenta.
Topics: Pregnancy; Female; Humans; Oxytocin; Receptors, Oxytocin; Peripartum Period; Labor, Obstetric; Oxytocics; Labor, Induced
PubMed: 38462255
DOI: 10.1016/j.ajog.2023.04.011 -
Neuroscience Sep 2023Fibromyalgia (FM) is a syndrome characterized by chronic pain with depression as a frequent comorbidity. However, efficient management of the pain and depressive...
Fibromyalgia (FM) is a syndrome characterized by chronic pain with depression as a frequent comorbidity. However, efficient management of the pain and depressive symptoms of FM is lacking. Given that endogenous oxytocin (OXT) contributes to the regulation of pain and depressive disorders, herein, we investigated the role of OXT in an experimental reserpine-induced FM model. In FM model, OXT-monomeric red fluorescent protein 1 (OXT-mRFP1) transgenic rats exhibited increased depressive behavior and sensitivity in a mechanical nociceptive test, suggesting reduced pain tolerance. Additionally, the development of the FM-like phenotype in OXT-mRFP1 FM model rats was accompanied by a significant reduction in OXT mRNA expression in the magnocellular neurons of the paraventricular nucleus. OXT-mRFP1 FM model rats also had significantly fewer tryptophan hydroxylase (TPH)- and tyrosine hydroxylase (TH)-immunoreactive (ir) neurons as well as reduced serotonin and norepinephrine levels in the dorsal raphe and locus coeruleus. To investigate the effects of stimulating the endogenous OXT pathway, rats expressing OXT-human muscarinic acetylcholine receptor (hM3Dq)-mCherry designer receptors exclusively activated by designer drugs (DREADDs) were also assessed in the FM model. Treatment of these rats with clozapine-N-oxide (CNO), an hM3Dq-activating drug, significantly improved characteristic FM model-induced pathophysiological pain, but did not alter depressive-like behavior. The chemogenetically induced effects were reversed by pre-treatment with an OXT receptor antagonist, confirming the specificity of action via the OXT pathway. These results indicate that endogenous OXT may have analgesic effects in FM, and could be a potential target for effective pain management strategies for this disorder.
Topics: Rats; Humans; Animals; Oxytocin; Reserpine; Fibromyalgia; Luminescent Proteins; Pain; Rats, Transgenic; Neurons; Receptors, Oxytocin
PubMed: 37532013
DOI: 10.1016/j.neuroscience.2023.07.028 -
American Journal of Obstetrics and... Mar 2024Induction of labor is a widely used practice. From 2016 to 2019, >1 in 3 women giving birth in the United States did so after undergoing labor induction. The obvious... (Review)
Review
Induction of labor is a widely used practice. From 2016 to 2019, >1 in 3 women giving birth in the United States did so after undergoing labor induction. The obvious goal of labor induction is vaginal birth with minimal maternal or neonatal morbidity. To achieve this goal, criteria for failed labor induction are needed. Herein, we provide an evidence-based approach to safely prevent unnecessary cesarean deliveries for failed induction. Although there are no randomized trials comparing failed labor induction criteria, the observational data have been consistent: if the status of the mother and the fetus permits, at least 12 to 18 hours of oxytocin should be administered after membrane rupture before deeming an induction of labor to have failed because of nonprogression to the active phase of labor.
Topics: Infant, Newborn; Pregnancy; Female; Humans; United States; Labor, Induced; Oxytocin; Labor, Obstetric; Cesarean Section; Fetal Membranes, Premature Rupture
PubMed: 36848041
DOI: 10.1016/j.ajog.2021.06.103 -
American Journal of Obstetrics and... Mar 2024This review assessed the efficacy and safety of pharmacologic agents (prostaglandins, oxytocin, mifepristone, hyaluronidase, and nitric oxide donors) and mechanical... (Review)
Review
This review assessed the efficacy and safety of pharmacologic agents (prostaglandins, oxytocin, mifepristone, hyaluronidase, and nitric oxide donors) and mechanical methods (single- and double-balloon catheters, laminaria, membrane stripping, and amniotomy) and those generally considered under the rubric of complementary medicine (castor oil, nipple stimulation, sexual intercourse, herbal medicine, and acupuncture). A substantial body of published reports, including 2 large network meta-analyses, support the safety and efficacy of misoprostol (PGE1) when used for cervical ripening and labor induction. Misoprostol administered vaginally at doses of 50 μg has the highest probability of achieving vaginal delivery within 24 hours. Regardless of dosing, route, and schedule of administration, when used for cervical ripening and labor induction, prostaglandin E2 seems to have similar efficacy in decreasing cesarean delivery rates. Globally, although oxytocin represents the most widely used pharmacologic agent for labor induction, its effectiveness is highly dependent on parity and cervical status. Oxytocin is more effective than expectant management in inducing labor, and the efficacy of oxytocin is enhanced when combined with amniotomy. However, prostaglandins administered vaginally or intracervically are more effective in inducing labor than oxytocin. A single 200-mg oral tablet of mifepristone seems to represent the lowest effective dose for cervical ripening. The bulk of the literature assessing relaxin suggests this agent has limited benefit when used for this indication. Although intracervical injection of hyaluronidase may cause cervical ripening, the need for intracervical administration has limited the use of this agent. Concerning the vaginal administration of nitric oxide donors, including isosorbide mononitrate, isosorbide, nitroglycerin, and sodium nitroprusside, the higher incidence of side effects with these agents has limited their use. A synthetic hygroscopic cervical dilator has been found to be effective for preinduction cervical ripening. Although a pharmacologic agent may be administered after the use of the synthetic hygroscopic dilator, in an attempt to reduce the interval to vaginal delivery, concomitant use of mechanical and pharmacologic methods is being explored. Combining the use of a single-balloon catheter with dinoprostone, misoprostol, or oxytocin enhances the efficacy of these pharmacologic agents in cervical ripening and labor induction. The efficacy of single- and double-balloon catheters in cervical ripening and labor induction seems similar. To date, the combination of misoprostol with an intracervical catheter seems to be the best approach when balancing delivery times with safety. Although complementary methods are occasionally used by patients, given the lack of data documenting their efficacy and safety, these methods are rarely used in hospital settings.
Topics: Female; Humans; Pregnancy; Abortifacient Agents, Nonsteroidal; Cervical Ripening; Dinoprostone; Hyaluronoglucosaminidase; Labor, Induced; Mifepristone; Misoprostol; Nitric Oxide Donors; Oxytocics; Oxytocin
PubMed: 38462252
DOI: 10.1016/j.ajog.2023.02.009 -
Clinical Immunology (Orlando, Fla.) Mar 2024Osteoarthritis (OA) is a complex disease characterized by cartilage degeneration and persistent pain. Prostaglandin E2 (PGE2) plays a significant role in OA inflammation... (Review)
Review
Osteoarthritis (OA) is a complex disease characterized by cartilage degeneration and persistent pain. Prostaglandin E2 (PGE2) plays a significant role in OA inflammation and pain. Recent studies have revealed the significant role of PGE2-mediated skeletal interoception in the progression of OA, providing new insights into the pathogenesis and treatment of OA. This aspect also deserves special attention in this review. Additionally, PGE2 is directly involved in pathologic processes including aberrant subchondral bone remodeling, cartilage degeneration, and synovial inflammation. Therefore, celecoxib, a commonly used drug to alleviate inflammatory pain through inhibiting PGE2, serves not only as an analgesic for OA but also as a potential disease-modifying drug. This review provides a comprehensive overview of the discovery history, synthesis and release pathways, and common physiological roles of PGE2. We discuss the roles of PGE2 and celecoxib in OA and pain from skeletal interoception and multiple perspectives. The purpose of this review is to highlight PGE2-mediated skeletal interoception and refresh our understanding of celecoxib in the pathogenesis and treatment of OA.
Topics: Humans; Celecoxib; Dinoprostone; Osteoarthritis; Inflammation; Pain
PubMed: 38262526
DOI: 10.1016/j.clim.2024.109904 -
International Journal of Molecular... Aug 2023The ECM propagates processes in idiopathic pulmonary fibrosis (IPF), leading to progressive lung scarring. We established an IPF-conditioned matrix (IPF-CM) system as a... (Review)
Review
The ECM propagates processes in idiopathic pulmonary fibrosis (IPF), leading to progressive lung scarring. We established an IPF-conditioned matrix (IPF-CM) system as a platform for testing drug candidates. Here, we tested the involvement of a PGE2 and PDE4 inhibitor, Roflumilast, in the IPF-CM system. Primary normal/IPF tissue-derived human lung fibroblasts (N/IPF-HLFs) were cultured on Matrigel and then removed to create the IPF-CM. N-HLFs were exposed to the IPF-CM/N-CM with/without PGE2 (1 nM) and Roflumilast (1 µM) for 24 h. The effect of the IPF-CM on cell phenotype and pro-fibrotic gene expression was tested. In addition, electronic records of 107 patients with up to 15-year follow-up were retrospectively reviewed. Patients were defined as slow/rapid progressors using forced vital capacity (FVC) annual decline. Medication exposure was examined. N-HLFs cultured on IPF-CM were arranged in large aggregates as a result of increased proliferation, migration and differentiation. A PGE2 and Roflumilast combination blocked the large aggregate formation induced by the IPF-CM ( < 0.001) as well as cell migration, proliferation, and pro-fibrotic gene expression. A review of patient records showed that significantly more slow-progressing patients were exposed to NSAIDs ( = 0.003). PGE2/PDE4 signaling may be involved in IPF progression. These findings should be further studied.
Topics: Humans; Dinoprostone; Retrospective Studies; Cells, Cultured; Idiopathic Pulmonary Fibrosis; Lung; Fibroblasts; Fibrosis
PubMed: 37569768
DOI: 10.3390/ijms241512393 -
Scientific Reports Oct 2023Oxytocin (OXT) is a neuropeptide hormone termed "love hormone" produced and released during childbirth and lactation. It is also produced in response to skin stimulation...
Oxytocin (OXT) is a neuropeptide hormone termed "love hormone" produced and released during childbirth and lactation. It is also produced in response to skin stimulation (e.g., during hugging and massaging) and music therapy. The effects of OXT on various organs have been revealed in recent years; however, the relationship between hair follicles and OXT remains unclear. In this study, we examined the effects of OXT on dermal papilla (DP) cells that control hair growth by secreting growth/regression signals. Gene expression analysis revealed that DP signature markers were significantly upregulated in DP cells treated with OXT. In addition, we tested the hair growth-promoting effects of OXT using in vitro hair follicle organoids. OXT promoted the growth of hair peg-like sprouting by upregulating the expression of growth-promoting factors, including genes encoding vascular endothelial growth factor A (VEGFA). This study highlights the positive effects of OXT in hair follicles and may assist in the development of new treatments for alopecia.
Topics: Female; Humans; Dermis; Oxytocin; Vascular Endothelial Growth Factor A; Cells, Cultured; Hair Follicle; Hair
PubMed: 37863919
DOI: 10.1038/s41598-023-40521-x -
Biochemical Pharmacology Nov 2023This review article summarizes the role of prostaglandin E (PGE) and its receptors (EP1-EP4) as it relates to the inflammatory cardiomyopathy, myocarditis. During the... (Review)
Review
This review article summarizes the role of prostaglandin E (PGE) and its receptors (EP1-EP4) as it relates to the inflammatory cardiomyopathy, myocarditis. During the COVID-19 pandemic, the onset of myocarditis in a subset of patients prompted a debate on the use of nonsteroidal anti-inflammatory drugs (NSAIDs), like ibuprofen, which act to inhibit the actions of prostaglandins. This review aims to further understanding of the role of PGE in the pathogenesis or protection of the myocardium in myocarditis. Inflammatory cardiomyopathies encompass a broad spectrum of disorders, all characterized by cardiac inflammation. Therefore, for the purpose of this review, the authors have placed particular emphasis on etiologies of myocarditis where effects of PGE have been documented.
Topics: Humans; Myocarditis; Pandemics; Receptors, Prostaglandin E, EP4 Subtype; Dinoprostone; Prostaglandins
PubMed: 37722627
DOI: 10.1016/j.bcp.2023.115813 -
Journal of Neuroendocrinology Sep 2023The fitness benefits of social life depend on the ability of animals to affiliate with others and form groups, on dominance hierarchies within groups that determine... (Review)
Review
The fitness benefits of social life depend on the ability of animals to affiliate with others and form groups, on dominance hierarchies within groups that determine resource distribution, and on cognitive capacities for recognition, learning and information transfer. The evolution of these phenotypes is coupled with that of neuroendocrine mechanisms, but the causal link between the two remains underexplored. Growing evidence from our research group and others demonstrates that the tools available in zebrafish, Danio rerio, can markedly facilitate progress in this field. Here, we review this evidence and provide a synthesis of the state-of-the-art in this model system. We discuss the involvement of generalized motivation and cognitive components, neuroplasticity and functional connectivity across social decision-making brain areas, and how these are modulated chiefly by the oxytocin-vasopressin neuroendocrine system, but also by reward-pathway monoamine signaling and the effects of sex-hormones and stress physiology.
Topics: Animals; Zebrafish; Neuroendocrinology; Brain; Motivation; Oxytocin
PubMed: 37165563
DOI: 10.1111/jne.13280 -
Current Biology : CB Jan 2024Oxytocin has long been thought to play a substantial role in social behaviors, such as social attachment and parenting behavior. However, how oxytocin neurons respond to...
Oxytocin has long been thought to play a substantial role in social behaviors, such as social attachment and parenting behavior. However, how oxytocin neurons respond to social and non-social stimuli is largely unknown, especially in high temporal resolution. Here, we recorded the in vivo real-time responses of oxytocin neurons in the paraventricular nucleus of the hypothalamus (PVN) in freely behaving mice. Our results revealed that oxytocin neurons were activated more significantly by stressors than social stimuli. The activation of oxytocin neurons was precisely correlated with struggling behavior during stress. Furthermore, we found that oxytocin mediated stress-induced social memory impairment. Our results reveal an important role of PVN oxytocin neurons in stress-induced social amnesia.
Topics: Mice; Animals; Oxytocin; Hypothalamus; Paraventricular Hypothalamic Nucleus; Neurons; Receptors, Oxytocin; Memory Disorders
PubMed: 38103551
DOI: 10.1016/j.cub.2023.11.037