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Sudden Vasopressin Withdrawal Causing Transient Central Diabetes Insipidus: A Case Report.
Cureus
Ramakanth Pata, Nway Nway, Ilana K Logvinsky +2 more
Vasopressin is a peptide hormone produced by the hypothalamus and stored in the posterior pituitary. It is secreted in response to hypotension and hyperosmolarity. Vasopressin and its analogs have been widely used in vasodilatory shocks such as septic shock and cardiogenic shock. The sudden withdrawal of vasopressin after its prolonged use can lead to polyuria and rising sodium levels, which is concerning for the diagnosis of diabetic insipidus (DI); likely central rather than nephrogenic in origin. We present a case of diabetic insipidus following the sudden discontinuation of a prolonged vasopressin infusion for septic shock, which responded to tapering doses of desmopressin.
Knockdown of HIPK2 Attenuates Angiotensin II-Induced Cardiac Fibrosis in Cardiac Fibroblasts.
J Cardiovasc Pharmacol
Feng Xu, Bingbing Mao, Yan Li +1 more
Homeodomain-interacting protein kinase-2 (HIPK2), a member of an evolutionary conserved family of serine/threonine kinases, has been observed to be involved in the pathogenesis of fibrotic diseases. However, its role in cardiac fibrosis remains unclear. In this study, we assessed the effect of HIPK2 on cardiac fibroblasts (CFs) in response to angiotensin II (Ang II) stimulation. The results indicated that HIPK2 expression was significantly increased in Ang II-induced CFs in a dose-dependent manner. Then, HIPK2 was knocked down in CFs to evaluate the roles of HIPK2. Knockdown of HIPK2 suppressed cell proliferation and migration in Ang II-induced CFs. The Ang II-caused increase in expression of α-smooth muscle actin, a hallmark of myofibroblast differentiation, was decreased by knockdown of HIPK2. HIPK2 knockdown also reduced extracellular matrix production including type I collagen and connective tissue growth factor. Furthermore, knockdown of HIPK2 blocked the activation of TGF-β1/Smad pathway in Ang II-induced CFs. These data suggested that HIPK2 knockdown prevented the Ang II-induced activation of CFs through inhibiting TGF-β1/Smad pathway, indicating HIPK2 might be an antifibrosis target for the treatment of cardiac fibrosis.
Whole-cell biotransformation for large scale production of carcinine in Escherichia coli.
J Biotechnol
Man Zhao, Xiangting Song, Wei Liu +5 more
Carcinine is a natural imidazole-containing peptide derivative. It is widely used in the cosmetics industry as anti-aging supplement with antioxidant, anti-glycation and glycation reversal functions, and it also has a notable pharmacological effect as anti-tumor drug and in protection against retinopathy. However, a technological method for synthesis and production of carcinine has not been established. In this study, a whole-cell transformation system converting β-alanine and histamine to carcinine by the enzymes Ebony and phosphopantetheine transferase (Sfp) has been developed. The results revealed that the catalytic efficiency of the strain containing the fusion protein of Ebony and Sfp (Sfp-glycine-serine-glycine-Ebony, SGE) in Escherichia coli W3110 (WSGE strain) is significantly higher (7.45 mM) than the combinatorial strain of pET28a-ebony and pACYCDuet-sfp in E. coli BL21(DE3) (BSE strain) (2.17 mM). Under the optimal reaction conditions (25 ℃, pH 7.0, 12.5 g/L wet cells, 20 mM β-alanine and 40 mM histamine), the carcinine can be quickly synthesized within 24 h up to a concentration of 22.63 mM. To achieve a continuous and efficient conversion of the precursors, a batch-feeding catalysis was designed. With this system, β-alanine (40 mM) and histamine (40 mM) could be completely transformed to carcinine (40.34 mM) in 36 h with a productivity of 0.204 g/L h reaching a titer of 7.34 g/L. Hence, the batch-feeding whole-cell biocatalysis is a promising technology for the high yield production of carcinine which can promote the industrial production of carcinine.
Transcriptome profiling of kisspeptin neurons from the mouse arcuate nucleus reveals new mechanisms in estrogenic control of fertility.
Proc Natl Acad Sci U S A
Balázs Göcz, Éva Rumpler, Miklós Sárvári +20 more
Kisspeptin neurons in the mediobasal hypothalamus (MBH) are critical targets of ovarian estrogen feedback regulating mammalian fertility. To reveal molecular mechanisms underlying this signaling, we thoroughly characterized the estrogen-regulated transcriptome of kisspeptin cells from ovariectomized transgenic mice substituted with 17β-estradiol or vehicle. MBH kisspeptin neurons were harvested using laser-capture microdissection, pooled, and subjected to RNA sequencing. Estrogen treatment significantly (p.adj. < 0.05) up-regulated 1,190 and down-regulated 1,139 transcripts, including transcription factors, neuropeptides, ribosomal and mitochondrial proteins, ion channels, transporters, receptors, and regulatory RNAs. Reduced expression of the excitatory serotonin receptor-4 transcript (Htr4) diminished kisspeptin neuron responsiveness to serotonergic stimulation. Many estrogen-regulated transcripts have been implicated in puberty/fertility disorders. Patients (n = 337) with congenital hypogonadotropic hypogonadism (CHH) showed enrichment of rare variants in putative CHH-candidate genes (e.g., LRP1B, CACNA1G, FNDC3A). Comprehensive characterization of the estrogen-dependent kisspeptin neuron transcriptome sheds light on the molecular mechanisms of ovary-brain communication and informs genetic research on human fertility disorders.
Development of anti-somatostatin receptors CAR T cells for treatment of neuroendocrine tumors.
J Immunother Cancer
Barbara Mandriani, Eleonora Pellè, Francesco Mannavola +9 more
Neuroendocrine tumors (NETs) overexpress somatostatin receptors (SSTRs).
Pharmacotherapy in Cachexia: A Review of Endocrine Abnormalities and Steroid Pharmacotherapy.
J Pain Palliat Care Pharmacother
Magdalena Celichowska, Miłosz Miedziaszczyk, Katarzyna Lacka
Cachexia is a state of increased metabolism associated with high morbidity and mortality. Dysregulation of cytokines and hormone activity causes reduced protein synthesis and excessive protein breakdown. various treatments are available, depending on the primary disease and the patient's state. Besides pharmacological treatment, crucial is nutritional support as well as increasing physical activity. The main purpose of pharmacological treatment is to diminish inflammation, improve appetite and decrease muscle wasting. Therefore a lot of medications aim at proinflammatory cytokines such as Interferon-α or Tumor Necrosis Factor-β, but because of the complicated mechanism of cachexia, the range of targets is very wide. in cachexia treatment, use of corticosteroids is common, which improve appetite, diminish inflammation, inhibit prostaglandin metabolism, Interleukin-1 activity. They can also decrease protein synthesis and increase protein degradation, which can be prevented by resveratrol. Estrogen analogs, progesterone analogs, testosterone analogs, Selective Androgen Receptor Modulators (SARM), Angiotensin-Converting-Enzyme Inhibitors (ACEI), Nonsteroidal anti-inflammatory drugs (NSAIDs), thalidomide, melatonin, Growth Hormone Releasing Peptide-2 (GHRP-2) may play important role in wasting syndrome treatment as well. However, for the usage of some of them, evidence-based recommendations are not available. This review highlights current therapeutic options for cachexia with a specific focus on steroid therapy.
The Role of Kisspeptin in the Pathogenesis of Pregnancy Complications: A Narrative Review.
Int J Mol Sci
Magdalena Szydełko-Gorzkowicz, Elżbieta Poniedziałek-Czajkowska, Radzisław Mierzyński +2 more
Kisspeptins are the family of neuropeptide products of the KISS-1 gene that exert the biological action by binding with the G-protein coupled receptor 54 (GPR54), also known as the KISS-1 receptor. The kisspeptin level dramatically increases during pregnancy, and the placenta is supposed to be its primary source. The role of kisspeptin has already been widely studied in hypogonadotropic hypogonadism, fertility, puberty disorders, and insulin resistance-related conditions, including type 2 diabetes mellitus, polycystic ovary syndrome, and obesity. Gestational diabetes mellitus (GDM), preeclampsia (PE), preterm birth, fetal growth restriction (FGR), or spontaneous abortion affected 2 to 20% of pregnancies worldwide. Their occurrence is associated with numerous short and long-term consequences for mothers and newborns; hence, novel, non-invasive predictors of their development are intensively investigated. The study aims to present a comprehensive review emphasizing the role of kisspeptin in the most common pregnancy-related disorders and neonatal outcomes. The decreased level of kisspeptin is observed in women with GDM, FGR, and a high risk of spontaneous abortion. Nevertheless, there are still many inconsistencies in kisspeptin concentration in pregnancies with preterm birth or PE. Further research is needed to determine the usefulness of kisspeptin as an early marker of gestational and neonatal complications.
The roles of kisspeptin and neurokinin B in GnRH pulse generation in humans, and their potential clinical application.
J Neuroendocrinol
Richard A Anderson, Robert P Millar
The delivery of gonadotropin-releasing hormone (GnRH) in a pulsatile mode to the gonadotropes has long been known to be essential for normal reproductive function. There have been numerous studies aimed at dissecting out the mechanisms underlying GnRH pulse generation. The discovery of kisspeptin as an upstream regulator of GnRH attracted the possibility that pulsatile kisspeptin governed the pulsatile secretion of GnRH. Subsequent studies have shown the importance of the neurokinin B (NKB) system in modulating kisspeptin secretion and this GnRH. A number of studies in laboratory rodents have supported this notion. By contrast, we present data from clinical studies in men and women, in a range of contexts, showing that continuous infusion of kisspeptin 10 at receptor-saturating levels gives rise to an increase in luteinizing hormone (LH) (GnRH) pulse frequency. This has been demonstrated in normal healthy and hypogonadal men, in normal women during the mid-cycle LH surge, in men and women with mutations in the genes encoding NKB or its receptor, neurokinin 3 receptor (NK3R), in women with polycystic ovary syndrome treated with NK3R antagonist, and in women treated with NK3R antagonist during the LH surge. These finds indicate that pulsatile secretion and action of kisspeptin on GnRH neurons is not required for the generation of LH (GnRH) pulses in humans. We also report that there is an absence of desensitization in humans exposed to continuous infusion of kisspeptin-10 at receptor-saturating concentrations over 22 h and briefly review GnRH, kisspeptin and NKB analogs and their clinical application.
Polyaspartic acid, 2-acrylamido-2-Methyl propane sulfonic acid and sodium alginate based biocompatible stimuli responsive polymer gel for controlled release of GHK-Cu peptide for wound healing.
J Biomater Appl
Shilpa Sharma, Mohammad Faiyaz Anwar, Amit Kumar Dinda +3 more
Stimuli responsive polymer based on Polyaspartic acid, 2-Acrylamido-2-methylpropane sulfonic acid and sodium alginate (NaAlg) were synthesized using two cross-linkers Ethylene glycol dimethacrylate (EGDMA) and TMPTA (Trimethylolpropane triacrylate). The polymers were standardized and optimized to obtain a polymer with maximum swelling in distilled water, saline, glucose and solutions of varying pH. The synthesized polymer swelled well in distilled water, glucose solution and acidic- alkaline medium. The biocompatibility of the polymer was evaluated for blood compatibility and protein adsorption. The polymer with maximum swelling property was used for peptide release studies. The polymer was further used to study the peptide encapsulation and release efficiency of the polymeric material which was confirmed by FTIR, Scanning Emission Microscope and EDX. The encapsulation efficiency of the polymer for encapsulating (glycyl-l-histidyl-l-lysine-copper) GHK-Cu was observed to be 55.26% and peptide release of 51.84% was observed for Ethylene glycol dimethacrylate based polymer after 24 h whereas for Trimethylolpropane triacrylate based polymer the encapsulation efficiency was observed to be 49.6% and release was 39.01%. The EGDMA based polymer was further examined under in vivo studies in order to evaluate the efficiency of the synthesized polymer. The in vivo studies include wound closure, histopathological analysis, biochemical and toxicity assay. The material has shown promising results for both in vivo and in vitro studies.
Novel ADNP Syndrome Mice Reveal Dramatic Sex-Specific Peripheral Gene Expression With Brain Synaptic and Tau Pathologies.
Biol Psychiatry
Gidon Karmon, Shlomo Sragovich, Gal Hacohen-Kleiman +22 more
ADNP is essential for embryonic development. As such, de novo ADNP mutations lead to an intractable autism/intellectual disability syndrome requiring investigation.
Humanin attenuates palmitate-induced hepatic lipid accumulation and insulin resistance via AMPK-mediated suppression of the mTOR pathway.
Biochem Biophys Res Commun
ChangHyuk Kwon, Jaw Long Sun, Ji Hoon Jeong +1 more
The pathogenesis of non-alcoholic fatty liver disease (NAFLD) remains unclear. Humanin (HN), a cytoprotective polypeptide, reportedly exhibits neuroprotective effects via suppression of inflammation and improvement of insulin resistance in neurons. This study aim was to investigate effects of HN on lipid accumulation in the hepatocytes and insulin signaling, and explore the underlying mechanisms. Protein expression levels were analyzed by Western blotting. Hepatic lipid accumulation was confirmed by Oil red-O staining. We found that HN-treatment ameliorated palmitate-induced lipid accumulation, expression of lipogenesis-associated genes (processed SREBP1, FAS, and SCD1), cell death, and caspase 3 activity in hepatocytes in a dose-dependent manner. Additionally, HN attenuated palmitate-induced impairment of insulin signaling. HN enhanced AMPK phosphorylation, whereas it suppressed palmitate-induced phosphorylation of mTOR. AMPK knockdown by siRNA neutralized the effects of HN on palmitic acid-treated hepatocytes. Collectively, HN prevents palmitate-induced hepatic lipid accumulation, apoptosis, and insulin resistance via AMPK-mediated suppression of the mTOR/SREBP1 pathway, suggesting that it may serve as a potential therapeutic agent in NAFLD treatment.
Intrathecally administered substance P activated the spinal defecation center and enhanced colorectal motility in anesthetized rats.
Am J Physiol Gastrointest Liver Physiol
Kiyotada Naitou, Honoka Iwashita, Hiromi H Ueda +6 more
Noxious stimuli on the colorectum cause colorectal contractions through activation of descending monoaminergic pathways projecting from the supraspinal defecation center to the spinal defecation center. Since it is known that substance P is involved in the response to peripheral noxious stimuli in the spinal cord, we investigated the effects of intrathecally administered substance P at L6-S1 levels on colorectal motility in rats that were anesthetized with α-chloralose and ketamine. Intrathecally administered substance P enhanced colorectal motility, even after transection of the thoracic spinal cord at the T4 level. Severing the pelvic nerves, but not the colonic nerves, abolished substance P enhanced colorectal motility. In the spinal cord at L6-S1 levels, expression of mRNA coding neurokinin (NK) 1-3 receptors was detected by RT-PCR. Immunohistological experiments revealed that preganglionic neurons of the pelvic nerves express NK1 receptors, whereas expression of NK2 receptors was not found. In addition, substance P-containing fibers densely innervated around the preganglionic neurons expressing NK1 receptors. An intrathecally administered NK1 receptor antagonist (spantide) attenuated capsaicin-induced colorectal contractions. These results suggest that the colokinetic action of substance P is mediated by the NK1 receptor in the spinal defecation center. Our findings indicate that substance P may function as a neurotransmitter in the spinal defecation center.NEW & NOTEWORTHY We found that intrathecally administered substance P enhanced colorectal motility in anesthetized rats. Neurokinin (NK) 1 receptors, but not NK2 receptors, were detected in preganglionic neurons of the pelvic nerves. Blockade of NK1 receptors in the spinal cord attenuated the enhanced colorectal motility in response to intracolonic noxious stimuli. The findings indicate that substance P may function as a neurotransmitter in the spinal reflex pathway controlling defecation.
Relaxin/serelaxin for cardiac dysfunction and heart failure in hypertension.
Adv Pharmacol
Prasad Chunduri, Shrey A Patel, Scott P Levick
The pregnancy related hormone relaxin is produced throughout the reproductive system. However, relaxin also has important cardiovascular effects as part of the adaptation that the cardiovascular system undergoes in response to the extra demands of pregnancy. These effects are primarily mediated by the relaxin family peptide receptor 1, which is one of four known relaxin receptors. The effects of relaxin on the cardiovascular system during pregnancy, as well as its anti-fibrotic and anti-inflammatory properties, have led to extensive studies into the potential of relaxin therapy as an approach to treat heart failure. Cardiomyocytes, cardiac fibroblasts, and endothelial cells all possess relaxin family peptide receptor 1, allowing for direct effects of therapeutic relaxin on the heart. Many pre-clinical animal studies have demonstrated a beneficial effect of exogenous relaxin on adverse cardiac remodeling including inflammation, fibrosis, cardiomyocyte hypertrophy and apoptosis, as well as effects on cardiac contractile function. Despite this, clinical studies have yielded disappointing results for the synthetic seralaxin, even though seralaxin was well tolerated. This article will provide background on relaxin in the context of normal physiology, as well as the role of relaxin in pregnancy-related adaptations of the cardiovascular system. We will also present evidence from pre-clinical animal studies that demonstrate the potential benefits of relaxin therapy, as well as discussing the results from clinical trials. Finally, we will discuss possible reasons for the failure of these clinical trials as well as steps being taken to potentially improve relaxin therapy for heart failure.
Female sexual dysfunctions: an overview on the available therapeutic interventions.
Minerva Obstet Gynecol
Lucia A da Silva Lara, Andrea C Rufino, Flávia F Oliveira +3 more
There are different types of female sexual dysfunctions (FSDs), and FSD in general has a high prevalence worldwide. Studies of FSD should consider it as a multifactorial disorder that has biological, psychological, environmental, and relational aspects. In this review we discuss the available therapeutic interventions for FSD.
Management of Hypertension with Female Sexual Dysfunction.
Medicina (Kaunas)
Qing Zhong, Yuri Anderson
Female sexual dysfunction (FSD) in hypertension has been less studied than male sexual dysfunction, and antihypertensive agents' impact on female sexual function is not defined. In this review, randomized double-blind clinical trials and cross-sectional studies related to female sexual function in hypertension were analyzed from 1991 to 2021. FSD appeared to be higher in hypertensive women than in normotensive women. Beta-blockers are the only antihypertensive agents with relatively strong evidence of damaging the female sexual function. Angiotensin receptor blockers (ARB) are relatively beneficial to female sexual function. To treat FSD in the presence of hypertension, controlling blood pressure is key, and the administration of angiotensin receptor blockers is preferred. In addition to controlling blood pressure, for premenopausal women, flibanserin and bremelanotide can be tried, while ospemifene and hormone supplements are preferred for postmenopausal women.
Role of the Ghrelin System in Colorectal Cancer.
Int J Mol Sci
Aldona Kasprzak
The ghrelin system contains several components (e.g., ghrelin with growing number of alternative peptides, growth hormone secretagogue receptors (GHS-Rs), and ghrelin-O-acyl-transferase (GOAT) and participates in regulation of a number of key processes of gastrointestinal (GI) tract cancer progression, including cell proliferation, migration, invasion, apoptosis, inflammation, and angiogenesis. However, its exact role in promoting or inhibiting cancer progression is still unclear. Colorectal cancer (CRC) is one of the most common human malignancies worldwide. Molecular studies suggest an autocrine/paracrine mechanism for the secretion of ghrelin in colorectal carcinogenesis and its contribution to its initial stages. However, the signalling pathways of CRC development involving the ghrelin system are poorly understood. Potential mechanisms of colon carcinogenesis involving components of the ghrelin system were previously described in an animal model and in in vitro studies. However, the diagnostic-prognostic role of serum ghrelin concentrations, tissue expression, or genetic changes of this system in various stages of CRC progression remains an open case. Thus, the aim of this study is to discuss the role of the ghrelin system in colon carcinogenesis, diagnostics and CRC prognostics, as well as the results of studies on the use of ghrelin and its analogues in the therapy of CRC-related syndromes (e.g., cachexia and sarcopenia).
Carnosine synthase deficiency in mice affects protein metabolism in skeletal muscle.
Biochem Biophys Res Commun
Jiawei Wu, Ai Egusa, Toshihide Nishimura
Carnosine and anserine are abundant peptides found in the skeletal muscle and nervous system in many vertebrates. Several in vitro and in vivo studies have demonstrate that exogenously administered carnosine improves exercise performance. Furthermore, carnosine is an antioxidant and antifatigue supplement. However, the physiological functions of endogenous carnosine and its related histidine-containing dipeptides in a living organism remain unclear. We aimed to clarify the physiological roles of endogenous carnosine by investigating the characteristics of carnosine synthase gene-deficient mice and the effects of carnosine on skeletal muscle protein metabolism. We discovered that carnosine and anserine were undetectable in the skeletal muscle of carnosine synthase knockout mice. We also quantified protein gene expression and enzyme levels in muscle protein metabolism. Gene and protein levels of the muscle protein synthesizer insulin-like growth factor-1 (IGF-1) and the degrading enzyme cathepsin B were markedly lower in carnosine synthase gene-deficient mice than those in wild-type mice. The amount of 3-methylhistidine (a marker for muscle proteolysis) in forced exercise and the weight of the gastrocnemius muscle were considerably lower in carnosine synthase gene-deficient mice than in wild-type mice. Consequently, we showed that carnosine deficiency affects weight maintenance and protein metabolism in skeletal muscle, suggesting that carnosine regulates skeletal muscle protein metabolism.
Chronic treatment with serelaxin mitigates adverse remodeling in a murine model of ischemic heart failure and modulates bioactive sphingolipid signaling.
Sci Rep
Teja Devarakonda, Juan Valle Raleigh, Adolfo G Mauro +3 more
Relaxin is a pleiotropic hormone demonstrated to confer cardioprotection in animal models of myocardial infarction and ischemic heart failure by modulating inflammation, fibrosis and arrhythmogenesis. Several of these pathways in the ischemic myocardium are intricately tied with the downstream signaling of bioactive sphingolipids, which play an active role during post-infarction remodeling. In this current study, we examined the effects of relaxin on sphingosine 1-phosphate (S1P), and the potential benefits of relaxin treatment on cardiac health in a rodent model of ischemic heart failure. Acute (30 min) and sub-acute (24 h) treatment of primary cardiomyocytes with serelaxin (recombinant human relaxin-2) increased the cardiomyocyte content of S1P. In the rodent model, treatment with relaxin for 28 days following myocardial ischemia by way of permanent left coronary artery occlusion improved survival and cardiac function, reduced fibrosis and apoptosis, and mitigated the expression of several pro-inflammatory and pro-fibrotic markers. The expression of beclin-1 (autophagy marker) was also reduced. The expression of S1P was significantly higher in cardiac tissue and plasma samples extracted from serelaxin-treated mice at day 28. In conclusion, our studies show a significant protection from relaxin in ischemic heart disease, and demonstrate the association between relaxin signaling and S1P generation.
In-silico Screening of Phytoconstituents on Wound Healing Targets - Approaches and Current Status.
Curr Drug Discov Technol
Vijaya Mandale, Asha Thomas, Ravindra Wavhale +1 more
Over recent years, there has been tremendous research focused on the effective utilization of natural products in wound management. Natural or herbal products contain several phytoconstituents that may act on various stages in wound healing and thereby provide a multi-targeted approach especially in the treatment of chronic wounds. Currently, attempts have been made to screen the phytoconstituents present in herbs on various targets involved in wound healing. This review includes a systematic evaluation of scientific reports by various groups of researchers on the herbals evaluated for wound management, their phytochemical profiling, pre-clinical studies, and molecular modeling studies. Various wound targets discussed include Interleukin-1, Interleukin-6, Tumor necrosis factor-α (TNF-α), Thymosin beta-4 (Tβ-4) that regulate the early inflammatory stage and the novel T cell immune response cDNA 7(TIRC7) that regulates angiogenesis. Also, neuropeptides P and Y act on the inflammatory, migratory, and proliferation phases, and growth factors like vascular endothelial growth factor family (VEGF) and placental growth factor family (PGF) are involved in angiogenesis, while the role of Fibroblast growth factor in tissue remodeling is discussed. As many of the natural products include polyherbal systems, this approach can help in the judicious selection of a combination of herbs that will act on multiple targets in the wound healing process and provide a multi-factorial approach in wound management.
The neurobiology of bremelanotide for the treatment of hypoactive sexual desire disorder in premenopausal women.
CNS Spectr
James G Pfaus, Amama Sadiq, Carl Spana +1 more
Hypoactive sexual desire disorder (HSDD) is a common female sexual dysfunction and is estimated to affect approximately 10% of women in the United States. It has been suggested that HSDD is associated with an imbalance of hormone and neurotransmitter levels in the brain, resulting in decreased excitation, increased inhibition, or a combination of both. Evidence suggests neurotransmitters, including dopamine (DA), norepinephrine, and serotonin, as well as hormones such as estradiol and testosterone, contribute to female sexual desire and response. Current treatments for HSDD include psychotherapy, and two US Food and Drug Administration-approved medications for premenopausal women: flibanserin, a serotonin mixed agonist and antagonist, and bremelanotide, a melanocortin receptor (MCR) agonist. Melanocortins are endogenous neuropeptides associated with the excitatory pathway of the female sexual response system. MCRs are found throughout the body, including the brain. Bremelanotide is an MCR agonist that nonselectively activates several of the receptor subtypes, of which subtype 4 (MC4R) is the most relevant at therapeutic doses. MC4R is predominantly expressed in the medial preoptic area (mPOA) of the hypothalamus in the brain, and is important for female sexual function. Animal studies suggest that bremelanotide may affect female sexual desire by activating presynaptic MC4Rs on neurons in the mPOA of the hypothalamus, leading to increased release of DA, an excitatory neurotransmitter that increases sexual desire. This review presents what is known about the mechanism of action of bremelanotide in the context of treating HSDD.