Journal articles on the topic 'Endocrine and local signalling pathways'
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Colella, Marco, Danila Cuomo, Antonia Giacco, Massimo Mallardo, Mario De Felice, and Concetta Ambrosino. "Thyroid Hormones and Functional Ovarian Reserve: Systemic vs. Peripheral Dysfunctions." Journal of Clinical Medicine 9, no. 6 (June 1, 2020): 1679. http://dx.doi.org/10.3390/jcm9061679.
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Thyroid hormones (THs) exert pleiotropic effects in different mammalian organs, including gonads. Genetic and non-genetic factors, such as ageing and environmental stressors (e.g., low-iodine intake, exposure to endocrine disruptors, etc.), can alter T4/T3 synthesis by the thyroid. In any case, peripheral T3, controlled by tissue-specific enzymes (deiodinases), receptors and transporters, ensures organ homeostasis. Conflicting reports suggest that both hypothyroidism and hyperthyroidism, assessed by mean of circulating T4, T3 and Thyroid-Stimulating Hormone (TSH), could affect the functionality of the ovarian reserve determining infertility. The relationship between ovarian T3 level and functional ovarian reserve (FOR) is poorly understood despite that the modifications of local T3 metabolism and signalling have been associated with dysfunctions of several organs. Here, we will summarize the current knowledge on the role of TH signalling and its crosstalk with other pathways in controlling the physiological and premature ovarian ageing and, finally, in preserving FOR. We will consider separately the reports describing the effects of circulating and local THs on the ovarian health to elucidate their role in ovarian dysfunctions.
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Matarazzo, Ilaria, Elena Toniato, and Iole Robuffo. "Psychobiome Feeding Mind: Polyphenolics in Depression and Anxiety." Current Topics in Medicinal Chemistry 18, no. 24 (January 16, 2019): 2108–15. http://dx.doi.org/10.2174/1568026619666181210151348.
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Recently gut bacterial populations seem to be involved in many functions and in the pathogenesis of several medical conditions. Traditionally the intestinal microbiome has been recognized to play an important role in metabolizing food compounds in simpler chemical structures for the absorption of different nutrients, and in maintenance control of gastrointestinal pathogens species. Bacterial populations are implicated in a complicated network of interactions within the immune system, epithelial cells local endocrine system, that affects the peripheral and the central nervous system, via blood circulation. Microbiome influencing the mind via immune, endocrine and metabolic signalling, is able to exert some clinical effects in different mental diseases. It releases endocrine substances through several pathways involved in the modulation of neuroinflammation and production of several neurotrasmitter precursors. It has recently been named psychobiome. It is known that phenolic compounds are able to influence microbiome proliferation and to exert several roles, especially regarding neuroinflammation in depressive and anxious behaviour. The clinical effects are reported in the literature. The aim of this study is to highlight the interaction between polyphenols and microbiota- gut-brain axis.
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Brandt, Claus, and Bente K. Pedersen. "The Role of Exercise-Induced Myokines in Muscle Homeostasis and the Defense against Chronic Diseases." Journal of Biomedicine and Biotechnology 2010 (2010): 1–6. http://dx.doi.org/10.1155/2010/520258.
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Chronic inflammation is involved in the pathogenesis of insulin resistance, atherosclerosis, neurodegeneration, and tumour growth. Regular exercise offers protection against type 2 diabetes, cardiovascular diseases, colon cancer, breast cancer, and dementia. Evidence suggests that the protective effect of exercise may to some extent be ascribed to the antiinflammatory effect of regular exercise. Here we suggest that exercise may exert its anti-inflammatory effect via a reduction in visceral fat mass and/or by induction of an anti-inflammatory environment with each bout of exercise. According to our theory, such effects may in part be mediated via muscle-derived peptides, so-called “myokines”. Contracting skeletal muscles release myokines with endocrine effects, mediating direct anti-inflammatory effects, and/or specific effects on visceral fat. Other myokines work locally within the muscle and exert their effects on signalling pathways involved in fat oxidation and glucose uptake. By mediating anti-inflammatory effects in the muscle itself, myokines may also counteract TNF-driven insulin resistance. In conclusion, exercise-induced myokines appear to be involved in mediating both systemic as well as local anti-inflammatory effects.
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Ziliotto, Silvia, Julia M. W. Gee, Ian O. Ellis, Andrew R. Green, Pauline Finlay, Anna Gobbato, and Kathryn M. Taylor. "Activated zinc transporter ZIP7 as an indicator of anti-hormone resistance in breast cancer." Metallomics 11, no. 9 (2019): 1579–92. http://dx.doi.org/10.1039/c9mt00136k.
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Drew, Janice E. "Signalling Pathways Implicated in Obesity Associated Cancers." Open Obesity Journal 6, no. 1 (September 3, 2014): 44–49. http://dx.doi.org/10.2174/1876823701406010044.
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Intensive research over recent years has provided irrefutable evidence of links between obesity and the risk of an increasing number of human cancers. The predicted economic burden is causing significant concern. This has prompted investigation of the underlying mechanisms with a focus on deregulated metabolic pathways. A number of metabolic processes and associated signalling pathways are associated with the development of obesity. These include a number of interlinking pathways regulating endocrine, redox, inflammation, immunity and lipogenic processes. The identification of deregulated metabolic pathways in obesity with promotion of carcinogenesis has targeted research on the signalling molecules involved. Consequently this mini review is focused on aberrant signalling of deregulated pathways provoked by diets that lead to obesity and their role in carcinogenesis. Knowledge of the signalling molecules involved will assist in directing and establishing dietary manipulation strategies to restore metabolic health in obese individuals. Importantly the identified diversity of signalling pathways linked to obesity related cancers will permit design of more effective combinatorial and multi-targeted cancer therapies in the future.
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Almstedt, Katrin, and Marcus Schmidt. "Targeted Therapies Overcoming Endocrine Resistance in Hormone Receptor-Positive Breast Cancer." Breast Care 10, no. 3 (2015): 168–72. http://dx.doi.org/10.1159/000405017.
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Breast cancer is a heterogeneous disease with different molecular subtypes. Most tumours are hormone receptor positive (luminal subtype) with potential endocrine responsiveness. Endocrine therapy is commonly used in these patients. Disease progression caused by endocrine resistance represents a significant challenge in the treatment of breast cancer. To understand the mechanisms of resistance of long-term oestrogen-deprived breast cancer cells, it is important to focus on cross-talk between steroid receptor signalling and other growth factor receptors and intracellular pathways. (Pre-)clinical trials showed that co-targeting these pathways can restore endocrine sensitivity. The focus of the current review is on the intracellular PI3K/AKT/mTOR signalling pathway and cyclin-dependant kinases (CDKs) in oestrogen receptor (ER)-positive breast cancer. Study results clearly show that both inhibition of the PI3K/AKT/mTOR pathway and CDK4/6 are promising ways to improve the efficacy of endocrine treatment in ER-positive breast cancer patients with comparably few side effects. Further clinical trials are needed to identify the patient population who would benefit most from a dual inhibition.
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AlFakeeh, A., and C. Brezden-Masley. "Overcoming endocrine resistance in hormone receptor–positive breast cancer." Current Oncology 25 (June 14, 2018): 18. http://dx.doi.org/10.3747/co.25.3752.
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Endocrine therapy, a major modality in the treatment of hormone receptor (hr)–positive breast cancer (bca), has improved outcomes in metastatic and nonmetastatic disease. However, a limiting factor to the use of endocrine therapy in bca is resistance resulting from the development of escape pathways that promote the survival of cancer cells despite estrogen receptor (er)–targeted therapy. The resistance pathways involve extensive cross-talk between er and receptor tyrosine kinase growth factors [epidermal growth factor receptor, human epidermal growth factor receptor 2 (her2), and insulin-like growth factor 1 receptor] and their downstream signalling pathways—most notably pi3k/akt/mtor and mapk. In some cases, resistance develops as a result of genetic or epigenetic alterations in various components of the signalling pathways, such as overexpression of her2 and erα co-activators, aberrant expression of cell-cycle regulators, and PIK3CA mutations. By combining endocrine therapy with various molecularly targeted agents and signal transduction inhibitors, some success has been achieved in overcoming and modulating endocrine resistance in hr-positive bca. Established strategies include selective er downregulators, anti-her2 agents, mtor (mechanistic target of rapamycin) inhibitors, and inhibitors of cyclin-dependent kinases 4 and 6. Inhibitors of pi3ka are not currently a treatment option for women with hr-positive bca outside the context of clinical trial. Ongoing clinical trials are exploring more agents that could be combined with endocrine therapy, and biomarkers that would help to guide decision-making and maximize clinical efficacy. In this review article, we address current treatment strategies for endocrine resistance, and we highlight future therapeutic targets in the endocrine pathway of bca.
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Bao, Haibo, Hui Zhu, Peihan Yu, Guanghua Luo, Ru Zhang, Qian Yue, and Jichao Fang. "Time-Series Transcriptomic Analysis Reveals the Molecular Profiles of Diapause Termination Induced by Long Photoperiods and High Temperature in Chilo suppressalis." International Journal of Molecular Sciences 23, no. 20 (October 14, 2022): 12322. http://dx.doi.org/10.3390/ijms232012322.
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Survival and adaptation to seasonal changes are challenging for insects. Many temperate insects such as the rice stem borer (Chilo suppressalis) overcome the adverse situation by entering diapause, wherein development changes dynamically occur and metabolic activity is suppressed. The photoperiod and temperature act as major environmental stimuli of diapause. However, the physiological and molecular mechanisms that interpret the ecologically relevant environmental cues in ontogenetic development during diapause termination are poorly understood. Here, we used genome-wide high-throughput RNA-sequencing to examine the patterns of gene expression during diapause termination in C. suppressalis. Major shifts in biological processes and pathways including metabolism, environmental information transmission, and endocrine signalling were observed across diapause termination based on over-representation analysis, short time-series expression miner, and gene set enrichment analysis. Many new pathways were identified in diapause termination including circadian rhythm, MAPK signalling, Wnt signalling, and Ras signalling, together with previously reported pathways including ecdysteroid, juvenile hormone, and insulin/insulin-like signalling. Our results show that convergent biological processes and molecular pathways of diapause termination were shared across different insect species and provided a comprehensive roadmap to better understand diapause termination in C. suppressalis.
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SKOUDY, Anouchka, Meritxell ROVIRA, Pierre SAVATIER, Franz MARTIN, Trinidad LEÓN-QUINTO, Bernat SORIA, and Francisco X. REAL. "Transforming growth factor (TGF)beta, fibroblast growth factor (FGF) and retinoid signalling pathways promote pancreatic exocrine gene expression in mouse embryonic stem cells." Biochemical Journal 379, no. 3 (May 1, 2004): 749–56. http://dx.doi.org/10.1042/bj20031784.
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Extracellular signalling cues play a major role in the activation of differentiation programmes. Mouse embryonic stem (ES) cells are pluripotent and can differentiate into a wide variety of specialized cells. Recently, protocols designed to induce endocrine pancreatic differentiation in vitro have been designed but little information is currently available concerning the potential of ES cells to differentiate into acinar pancreatic cells. By using conditioned media of cultured foetal pancreatic rudiments, we demonstrate that ES cells can respond in vitro to signalling pathways involved in exocrine development and differentiation. In particular, modulation of the hedgehog, transforming growth factor β, retinoid, and fibroblast growth factor pathways in ES cell-derived embryoid bodies (EB) resulted in increased levels of transcripts encoding pancreatic transcription factors and cytodifferentiation markers, as demonstrated by RT-PCR. In EB undergoing spontaneous differentiation, expression of the majority of the acinar genes (i.e. amylase, carboxypeptidase A and elastase) was induced after the expression of endocrine genes, as occurs in vivo during development. These data indicate that ES cells can undergo exocrine pancreatic differentiation with a kinetic pattern of expression reminiscent of pancreas development in vivo and that ES cells can be coaxed to express an acinar phenotype by activation of signalling pathways known to play a role in pancreatic development and differentiation.
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Edwin Thanarajah, Sharmili, and Marc Tittgemeyer. "Food reward and gut-brain signalling." Neuroforum 26, no. 1 (February 25, 2020): 1–9. http://dx.doi.org/10.1515/nf-2019-0020.
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AbstractThe increasing availability of ultra-processed, energy dense food is contributing to the spread of the obesity pandemic, which is a serious health threat in today’s world. One possible cause for this association arises from the fact that the brain is wired to derive pleasure from eating. Specifically, food intake activates reward pathways involving dopamine receptor signalling. The reinforcing value of specific food items results from the interplay between taste and nutritional properties. Increasing evidence suggests that nutritional value is sensed in the gut by chemoreceptors in the intestinal tract and the hepatic portal vein, and conveyed to the brain through neuronal and endocrine pathways to guide food selection behaviour. Ultra-processed food is designed to potentiate the reward response through a combination of high fat and high sugar, therebye seeming highly appetizing. There is increasing evidence that overconsumption of processed food distorts normal reward signalling, leading to compulsive eating behaviour and obesity. Hence, it is essential to understand food reward and gut-brain signalling to find an effective strategy to combat the obesity pandemic.
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Cripps, Samuel M., Deidre M. Mattiske, and Andrew J. Pask. "Erectile Dysfunction in Men on the Rise: Is There a Link with Endocrine Disrupting Chemicals?" Sexual Development 15, no. 1-3 (2021): 187–212. http://dx.doi.org/10.1159/000516600.
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Erectile dysfunction (ED) is one of the most prevalent chronic conditions affecting men. ED can arise from disruptions during development, affecting the patterning of erectile tissues in the penis and/or disruptions in adulthood that impact sexual stimuli, neural pathways, molecular changes, and endocrine signalling that are required to drive erection. Sexual stimulation activates the parasympathetic system which causes nerve terminals in the penis to release nitric oxide (NO). As a result, the penile blood vessels dilate, allowing the penis to engorge with blood. This expansion subsequently compresses the veins surrounding the erectile tissue, restricting venous outflow. As a result, the blood pressure localised in the penis increases dramatically to produce a rigid erection, a process known as tumescence. The sympathetic pathway releases noradrenaline (NA) which causes detumescence: the reversion of the penis to the flaccid state. Androgen signalling is critical for erectile function through its role in penis development and in regulating the physiological processes driving erection in the adult. Interestingly, estrogen signalling is also implicated in penis development and potentially in processes which regulate erectile function during adulthood. Given that endocrine signalling has a prominent role in erectile function, it is likely that exposure to endocrine disrupting chemicals (EDCs) is a risk factor for ED, although this is an under-researched field. Thus, our review provides a detailed description of the underlying biology of erectile function with a focus on the role of endocrine signalling, exploring the potential link between EDCs and ED based on animal and human studies.
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Spencer, Sarah J., Abdeslam Mouihate, and Quentin J. Pittman. "Neonatal neuroimmune challenge effects on adult brain derived neurotrophic factor signalling pathways." Frontiers in Neuroendocrinology 27, no. 1 (May 2006): 107–8. http://dx.doi.org/10.1016/j.yfrne.2006.03.267.
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Xu, Wenting, Mengyu Tang, Jiahui Wang, and Lihong Wang. "Identification of the Active Constituents and Significant Pathways of Cangfu Daotan Decoction for the Treatment of PCOS Based on Network Pharmacology." Evidence-Based Complementary and Alternative Medicine 2020 (February 22, 2020): 1–15. http://dx.doi.org/10.1155/2020/4086864.
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Background. Polycystic ovary syndrome (PCOS) is the most common female endocrine disease. Cangfu Daotan Decoction (CDD) can effectively relieve the clinical symptoms of PCOS patients. Methods. To explore the active ingredients and related pathways of CDD for treating PCOS, a network pharmacology-based analysis was carried out. The active ingredients of CDD and their potential targets were obtained from the TCM system pharmacology analysis platform. The obtained PCOS-related genes from OMIM and GeneCards were imported to establish protein-protein interaction networks in STRING. Finally, GO analysis and significant pathway analysis were conducted with the RStudio (Bioconductor) database. Results. A total of 111 active compounds were obtained from 1433 ingredients present in the CDD, related to 118 protein targets. In addition, 736 genes were found to be closely related to PCOS, of which 44 overlapped with CDD and were thus considered therapeutically relevant. Pathway enrichment analysis identified the AGE-RAGE signalling pathway in diabetic complications, endocrine resistance, the IL-17 signalling pathway, the prolactin signalling pathway, and the HIF-1 signalling pathway. Moreover, PI3K-Akt, insulin resistance, Toll-like receptor, MAPK, and AGE-RAGE were related to PCOS and treatment. Conclusions. CDD can effectively improve the symptoms of PCOS, and our network pharmacological analysis lays the foundation for future clinical research.
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Slominski, Andrzej, Michal Zmijewski, Igor Semak, Blazej Zbytek, Alexander Pisarchik, Wei Li, Jordan Zjawiony, and Robert Tuckey. "Cytochromes P450 and Skin Cancer: Role of Local Endocrine Pathways." Anti-Cancer Agents in Medicinal Chemistry 14, no. 1 (January 31, 2014): 77–96. http://dx.doi.org/10.2174/18715206113139990308.
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Weiss, Linda C., Florian Leese, Christian Laforsch, and Ralph Tollrian. "Dopamine is a key regulator in the signalling pathway underlying predator-induced defences in Daphnia." Proceedings of the Royal Society B: Biological Sciences 282, no. 1816 (October 7, 2015): 20151440. http://dx.doi.org/10.1098/rspb.2015.1440.
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The waterflea Daphnia is a model to investigate the genetic basis of phenotypic plasticity resulting from one differentially expressed genome. Daphnia develops adaptive phenotypes (e.g. morphological defences) thwarting predators, based on chemical predator cue perception. To understand the genomic basis of phenotypic plasticity, the description of the precedent cellular and neuronal mechanisms is fundamental. However, key regulators remain unknown. All neuronal and endocrine stimulants were able to modulate but not induce defences, indicating a pathway of interlinked steps. A candidate able to link neuronal with endocrine responses is the multi-functional amine dopamine. We here tested its involvement in trait formation in Daphnia pulex and Daphnia longicephala using an induction assay composed of predator cues combined with dopaminergic and cholinergic stimulants. The mere application of both stimulants was sufficient to induce morphological defences. We determined dopamine localization in cells found in close association with the defensive trait. These cells serve as centres controlling divergent morphologies. As a mitogen and sclerotization agent, we anticipate that dopamine is involved in proliferation and structural formation of morphological defences. Furthermore, dopamine pathways appear to be interconnected with endocrine pathways, and control juvenile hormone and ecdysone levels. In conclusion, dopamine is suggested as a key regulator of phenotypic plasticity.
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Links, Thera P., Hans H. G. Verbeek, Robert M. W. Hofstra, and John Th M. Plukker. "ENDOCRINE TUMOURS: Progressive metastatic medullary thyroid carcinoma: first- and second-line strategies." European Journal of Endocrinology 172, no. 6 (June 2015): R241—R251. http://dx.doi.org/10.1530/eje-14-0726.
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The treatment for metastasised medullary thyroid cancer is still a topic of discussion. One of the main challenges remains to find effective adjuvant and palliative options for patients with metastatic disease. The diagnostic and treatment strategies for this tumour are discussed and possible new developments commented. Approaches that target rearranged during transfection (RET) are preferable to those that target RET downstream proteins as, theoretically, blocking RET downstream targets will block only one of the many pathways activated by RET. Combining several agents would seem to be more promising, in particular agents that target RET with those that independently target RET signalling pathways or the more general mechanism of tumour progression.
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Capurso, Gabriele, Alessia Di Florio, Claudio Sette, and Gianfranco Delle Fave. "Signalling Pathways Passing Src in Pancreatic Endocrine Tumours: Relevance for Possible Combined Targeted Therapies." Neuroendocrinology 97, no. 1 (2013): 67–73. http://dx.doi.org/10.1159/000336093.
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Gee, J. M. W., A. Howell, W. J. Gullick, C. C. Benz, R. L. Sutherland, R. J. Santen, L.-A. Martin, et al. "Consensus Statement." Endocrine-Related Cancer 12, Supplement_1 (July 2005): S1—S7. http://dx.doi.org/10.1677/erc.1.01054.
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Anti-hormones (notably tamoxifen), chemotherapy and modern radiotherapeutic approaches are invaluable in the management of breast cancer, and collectively have contributed substantially to the improved survival in this disease. Moreover, there is promise that these successes will continue with the emergence of other endocrine agents (for example, aromatase inhibitors and pure anti-oestrogens). However, de novo and acquired resistance comprises a significant problem with all treatment approaches examined to date. This Workshop aimed to evaluate the contribution made by growth factor signalling pathways in the various resistant states, primarily focusing on resistance to anti-hormonal strategies and spanning experimental models and, where possible, clinical breast cancer data. The successes and limitations of therapeutic targeting of these pathways with various signal transduction inhibitors (STIs) were evaluated in model systems and from emerging clinical trials (including epidermal growth factor receptor inhibitors such as gefitinib). It was concluded that growth factor signalling is an important contributor in the development of endocrine resistance in breast cancer and that use of STIs provides a promising therapeutic strategy for this disease. However, the cancer cell is clearly able to harness alternative growth factor signalling pathways for growth and cell survival in the presence of STI monotherapy and, as a consequence, the efficacy of STIs is likely to be limited by the acquisition of resistance. A number of strategies were proposed from studies in model systems that appeared to enhance anti-tumour actions of existing STI monotherapy, notably including combination therapies targeting multiple pathways. With the increased availability of diverse STIs and improved drug delivery, there is much hope that the more complex therapeutic strategies proposed may ultimately be achievable in clinical practice.
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Jabbour, Henry N., Rodney W. Kelly, Hamish M. Fraser, and Hilary O. D. Critchley. "Endocrine Regulation of Menstruation." Endocrine Reviews 27, no. 1 (September 13, 2005): 17–46. http://dx.doi.org/10.1210/er.2004-0021.
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In women, endometrial morphology and function undergo characteristic changes every menstrual cycle. These changes are crucial for perpetuation of the species and are orchestrated to prepare the endometrium for implantation of a conceptus. In the absence of pregnancy, the human endometrium is sloughed off at menstruation over a period of a few days. Tissue repair, growth, angiogenesis, differentiation, and receptivity ensue to prepare the endometrium for implantation in the next cycle. Ovarian sex steroids through interaction with different cognate nuclear receptors regulate the expression of a cascade of local factors within the endometrium that act in an autocrine/paracrine and even intracrine manner. Such interactions initiate complex events within the endometrium that are crucial for implantation and, in the absence thereof, normal menstruation. A clearer understanding of regulation of normal endometrial function will provide an insight into causes of menstrual dysfunction such as menorrhagia (heavy menstrual bleeding) and dysmenorrhea (painful periods). The molecular pathways that precipitate these pathologies remain largely undefined. Future research efforts to provide greater insight into these pathways will lead to the development of novel drugs that would target identified aberrations in expression and/or of local uterine factors that are crucial for normal endometrial function.
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García-Jiménez, Custodia, and Pilar Santisteban. "TSH signalling and cancer." Arquivos Brasileiros de Endocrinologia & Metabologia 51, no. 5 (July 2007): 654–71. http://dx.doi.org/10.1590/s0004-27302007000500003.
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Thyroid cancers are the most frequent endocrine neoplasms and mutations in the thyrotropin receptor (TSHR) are unusually frequent. Here we present the state-of-the-art concerning the role of TSHR in thyroid cancer and discuss it in light of the cancer stem cell theory or the classical view. We briefly review the gene and protein structure updating the cancer related TSHR mutations database. Intriguingly, hyperfunctioning TSHR mutants characterise differentiated cancers in contrast to undifferentiated thyroid cancers which very often bear silenced TSHR. It remains unclear whether TSHR alterations in thyroid cancers play a role in the onset or they appear as a consequence of genetic instability during evolution, but the presence of functional TSHR is exploited in therapy. We outline the signalling network build up in the thyrocyte between TSHR/PKA and other proliferative pathways such as Wnt, PI3K and MAPK. This network’s integrity surely plays a role in the onset/evolution of thyroid cancer and needs further research. Lastly, future investigation of epigenetic events occurring at the TSHR and other loci may give better clues for molecular based therapy of undifferentiated thyroid carcinomas. Targeted demethylating agents, histone deacetylase inhibitors combined with retinoids and specific RNAis may help treatment in the future.
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Lewitt, Moira S., and Gary W. Boyd. "The Role of Insulin-Like Growth Factors and Insulin-Like Growth Factor–Binding Proteins in the Nervous System." Biochemistry Insights 12 (January 2019): 117862641984217. http://dx.doi.org/10.1177/1178626419842176.
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The insulin-like growth factors (IGF-I and IGF-II) and their receptors are widely expressed in nervous tissue from early embryonic life. They also cross the blood brain barriers by active transport, and their regulation as endocrine factors therefore differs from other tissues. In brain, IGFs have paracrine and autocrine actions that are modulated by IGF-binding proteins and interact with other growth factor signalling pathways. The IGF system has roles in nervous system development and maintenance. There is substantial evidence for a specific role for this system in some neurodegenerative diseases, and neuroprotective actions make this system an attractive target for new therapeutic approaches. In developing new therapies, interaction with IGF-binding proteins and other growth factor signalling pathways should be considered. This evidence is reviewed, gaps in knowledge are highlighted, and recommendations are made for future research.
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Lee, H. R., S. H. Hyun, E. B. Jeung, and K. C. Choi. "193 BISPHENOL A AND PHTHALATE ENHANCED THE GROWTH OF PROSTATE CANCER CELLS AND ALTERED TGF-β SIGNALING MOLECULES VIA AN ESTROGEN RECEPTOR OR ANDROGEN RECEPTOR-DEPENDENT PATHWAY IN IN VITRO AND IN VIVO MODELS." Reproduction, Fertility and Development 25, no. 1 (2013): 245. http://dx.doi.org/10.1071/rdv25n1ab193.
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Endocrine-disrupting chemicals (EDC) can bind to the hormone receptor and induce an unexpected hormone response to activate oestrogen receptor (ER)- and androgen receptor (AR)-mediated signalling pathways. Among EDC, bisphenol A (BPA) has a detrimental effect on the endocrine system and is suspected to promote human breast and ovarian cancers. Recent studies have reported that phthalate can disrupt the endocrine system and has a weak estrogenic activity with binding to ER. In this study, we demonstrated whether BPA and dibutyl phthalate (DBP) stimulate the proliferation of prostate cancer cells, LNCaP cells, which have both ER and AR. We evaluated the proliferative rate of LNCaP cells following BPA and DBP treatment using a cell viability assay compared with EtOH treatment as a negative control. Further, we examined the alteration of cell cycle-related gene expressions and TGF-β signalling molecules by semiquantitative RT-PCR. Both BPA and DBP increased LNCaP cell growth more than 2-fold. Moreover, these EDC altered transcriptional expressions of cell cycle-related genes, cyclin D1 and p21, at 6 h in LNCaP cells after exposure of BPA and DBP. Like 17β-oestradiol (E2) and dihydrotestosterone (DHP), treatments of BPA and DBP lead to an increase of the transcriptional levels of c-myc and c-fos in LNCaP cells from 30 min to 6 h. In addition, BPA and DBP decreased the protein level of not only p-smad but also total smad, suggesting that these EDC can affect the molecules of the TGF-β signalling pathway. It was of interest that these effects of EDC were reversed by an antagonist of ER or AR signalling pathways in these prostate cancer cells. These results suggest that BPA and phthalate can alter various gene expressions in TGF-β signalling molecules and stimulate cell growth in prostate cancer cells in vitro. In addition, the growth of prostate cancer cells was stimulated following the exposure of E2, DHT, and DBP in vivo. Taken together, these results indicate the potential of BPA and phthalate in the carcinogenesis of prostate cancer by the oestrogen or androgen-dependent signalling pathway. This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Ministry of Education, Science and Technology (MEST) of Korea government (no. 2011-0015385).
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Moyes, Amie J., and Adrian J. Hobbs. "C-Type Natriuretic Peptide: A Multifaceted Paracrine Regulator in the Heart and Vasculature." International Journal of Molecular Sciences 20, no. 9 (May 8, 2019): 2281. http://dx.doi.org/10.3390/ijms20092281.
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C-type natriuretic peptide (CNP) is an autocrine and paracrine mediator released by endothelial cells, cardiomyocytes and fibroblasts that regulates vital physiological functions in the cardiovascular system. These roles are conveyed via two cognate receptors, natriuretic peptide receptor B (NPR-B) and natriuretic peptide receptor C (NPR-C), which activate different signalling pathways that mediate complementary yet distinct cellular responses. Traditionally, CNP has been deemed the endothelial component of the natriuretic peptide system, while its sibling peptides, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), are considered the endocrine guardians of cardiac function and blood volume. However, accumulating evidence indicates that CNP not only modulates vascular tone and blood pressure, but also governs a wide range of cardiovascular effects including the control of inflammation, angiogenesis, smooth muscle and endothelial cell proliferation, atherosclerosis, cardiomyocyte contractility, hypertrophy, fibrosis, and cardiac electrophysiology. This review will focus on the novel physiological functions ascribed to CNP, the receptors/signalling mechanisms involved in mediating its cardioprotective effects, and the development of therapeutics targeting CNP signalling pathways in different disease pathologies.
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Sheldon, I. Martin, James G. Cronin, Gareth D. Healey, Christoph Gabler, Wolfgang Heuwieser, Dominik Streyl, John J. Bromfield, Akio Miyamoto, Chrys Fergani, and Hilary Dobson. "Innate immunity and inflammation of the bovine female reproductive tract in health and disease." REPRODUCTION 148, no. 3 (September 2014): R41—R51. http://dx.doi.org/10.1530/rep-14-0163.
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Mammalian reproductive physiology and the development of viviparity co-evolved with inflammation and immunity over millennia. Many inflammatory mediators contribute to paracrine and endocrine signalling, and the maintenance of tissue homeostasis in the female reproductive tract. However, inflammation is also a feature of microbial infections of the reproductive tract. Bacteria and viruses commonly cause endometritis, perturb ovarian follicle development and suppress the endocrine activity of the hypothalamus and pituitary in cattle. Innate immunity is an evolutionary ancient system that orchestrates host cell inflammatory responses aimed at eliminating pathogens and repairing damaged tissue. Pattern recognition receptors on host cells bind pathogen-associated molecular patterns and damage-associated molecular patterns, leading to the activation of intracellular MAPK and NFκB signalling pathways and the release of inflammatory mediators. Inflammatory mediators typically include the interleukin cytokines IL1β and IL6, chemokines such as IL8, interferons and prostaglandins. This review outlines the mechanisms of inflammation and innate immunity in the bovine female reproductive tract during health and disease condition.
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Stevens, K. G., C. A. Bader, A. Sorvina, D. A. Brooks, S. E. Plush, and J. L. Morrison. "Imaging and lipidomics methods for lipid analysis in metabolic and cardiovascular disease." Journal of Developmental Origins of Health and Disease 8, no. 5 (July 12, 2017): 566–74. http://dx.doi.org/10.1017/s2040174417000496.
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Cardiometabolic diseases exhibit changes in lipid biology, which is important as lipids have critical roles in membrane architecture, signalling, hormone synthesis, homoeostasis and metabolism. However,Developmental Origins of Health and Diseasestudies of cardiometabolic disease rarely include analysis of lipids. This short review highlights some examples of lipid pathology and then explores the technology available for analysing lipids, focussing on the need to develop imaging modalities for intracellular lipids. Analytical methods for studying interactions between the complex endocrine and intracellular signalling pathways that regulate lipid metabolism have been critical in expanding our understanding of how cardiometabolic diseases develop in association with obesity and dietary factors. Biochemical methods can be used to generate detailed lipid profiles to establish links between lifestyle factors and metabolic signalling pathways and determine how changes in specific lipid subtypes in plasma and homogenized tissue are associated with disease progression. New imaging modalities enable the specific visualization of intracellular lipid traffic and distributionin situ. These techniques provide a dynamic picture of the interactions between lipid storage, mobilization and signalling, which operate during normal cell function and are altered in many important diseases. The development of methods for imaging intracellular lipids can provide a dynamic real-time picture of how lipids are involved in complex signalling and other cell biology pathways; and how they ultimately regulate metabolic function/homoeostasis during early development. Some imaging modalities have the potential to be adapted forin vivoapplications, and may enable the direct visualization of progression of pathogenesis of cardiometabolic disease after poor growth in early life.
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Martin, Aline, Valentin David, and L. Darryl Quarles. "Regulation and Function of the FGF23/Klotho Endocrine Pathways." Physiological Reviews 92, no. 1 (January 2012): 131–55. http://dx.doi.org/10.1152/physrev.00002.2011.
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Calcium (Ca2+) and phosphate (PO43−) homeostasis are coordinated by systemic and local factors that regulate intestinal absorption, influx and efflux from bone, and kidney excretion and reabsorption of these ions through a complex hormonal network. Traditionally, the parathyroid hormone (PTH)/vitamin D axis provided the conceptual framework to understand mineral metabolism. PTH secreted by the parathyroid gland in response to hypocalcemia functions to maintain serum Ca2+ levels by increasing Ca2+ reabsorption and 1,25-dihydroxyvitamin D [1,25(OH)2D] production by the kidney, enhancing Ca2+ and PO43− intestinal absorption and increasing Ca2+ and PO43− efflux from bone, while maintaining neutral phosphate balance through phosphaturic effects. FGF23 is a recently discovered hormone, predominately produced by osteoblasts/osteocytes, whose major functions are to inhibit renal tubular phosphate reabsorption and suppress circulating 1,25(OH)2D levels by decreasing Cyp27b1-mediated formation and stimulating Cyp24-mediated catabolism of 1,25(OH)2D. FGF23 participates in a new bone/kidney axis that protects the organism from excess vitamin D and coordinates renal PO43− handling with bone mineralization/turnover. Abnormalities of FGF23 production underlie many inherited and acquired disorders of phosphate homeostasis. This review discusses the known and emerging functions of FGF23, its regulation in response to systemic and local signals, as well as the implications of FGF23 in different pathological and physiological contexts.
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Mao, Yiwen, Yan Li, Han Gao, and Xinda Lin. "The Direct Interaction between E93 and Kr-h1 Mediated Their Antagonistic Effect on Ovary Development of the Brown Planthopper." International Journal of Molecular Sciences 20, no. 10 (May 16, 2019): 2431. http://dx.doi.org/10.3390/ijms20102431.
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The juvenile hormone (JH) signalling and ecdysone signalling pathways are crucial endocrine signalling pathways that orchestrate the metamorphosis of insects. The metamorphic process, the morphological change from the immature to adult forms, is orchestrated by the dramatic reduction of JH and downstream transcription factors. The Krüppel-homologue 1 (Kr-h1), a downstream transcription factor of the JH signalling pathway, represses E93 expression with an anti-metamorphic effect. However, the biochemical interaction between Kr-h1 and E93 and how the interaction regulates ovary development, a sensitive readout for endocrine regulation, remain unknown. In brown planthopper, Nilaparvata lugens, we found that the downregulation of Kr-h1 partially recovered the deteriorating effect of E93 knock-down on metamorphosis. Dual knock down of E93 and Kr-h1 increased ovary development and the number of eggs laid when compared to the effects of the knock down of E93 alone, indicating that the knock down of Kr-h1 partially recovered the deteriorating effect of the E93 knock-down on ovary development. In summary, our results indicated that E93 and Kr-h1 have antagonistic effects on regulating metamorphosis and ovary development. We tested the biochemical interaction between these two proteins and found that these molecules interact directly. Kr-h1 V and E93 II undergo strong and specific interactions, indicating that the potential interacting domain may be located in these two regions. We inferred that the nuclear receptor interaction motif (NR-box) and helix-turn-helix DNA binding motifs of the pipsqueak family (RHF1) are candidate domains responsible for the protein–protein interaction between E93 and Kr-h1. Moreover, the HA-tagged E93 and FLAG-tagged Kr-h1 were co-localized in the nucleus, and the expression of E93 was increased when Kr-h1 was downregulated, supporting that these two proteins may interact antagonistically. JH and ecdysone signalling are critical for the control of ovary development and pest populations. Our result is important for understanding the interactions between E93 and related proteins, which makes it possible to identify potential targets and develop new pesticides for pest management.
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Dongre, Utpal Jagdish. "Adipokines in Insulin Resistance: Current Updates." Biosciences Biotechnology Research Asia 18, no. 2 (August 30, 2021): 357–66. http://dx.doi.org/10.13005/bbra/2922.
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Obesity is a chronic metabolic disease that affects both the pediatric and adult populations. Adipose tissue acts as an endocrine organ which secretes various adipokines involved in fat mass regulation and energy balance via modulating the metabolic signalling pathways. Altered secretion of adipokines promotes multiple complications, including insulin resistance. The primary mechanism of action that underlines the involvement of adipokines in the development of insulin resistance includes phosphorylation/de-phosphorylation of insulin receptor substrate-1 (IRS-1) facilitate by other signalling molecules like a suppressor of cytokine signalling 1 (SOCS-1). Adipokines mediated insulin resistance further contribute to the development of atherosclerosis, dyslipidemia, fatty liver disease, cancer etc. Thus, this review provides recent updates on the role of resistin, lipocalin-2, RBP-4, chemerin, TNF-alpha and IL-6 adipokines in the progression of insulin resistance.
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Igaz, Péter. "Genetics of neuroendocrine tumours, hereditary tumour syndromes." Orvosi Hetilap 154, no. 39 (September 2013): 1541–48. http://dx.doi.org/10.1556/oh.2013.29706.
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Neuroendocrine tumours occur in some hereditary tumour syndromes, and the molecular pathophysiological mechanisms involved in these are also important in their sporadic counterparts which representing the majority of neuroendocrine tumours. These syndromes include multiple endocrine neoplasia type 1, von Hippel–Lindau syndrome, neurofibromatosis type 1 and tuberous sclerosis. All these follow an autosomal dominant inheritance. The primarily affected molecular pathways are Ras-MAPK signalling, hypoxia induced factor 1α, and mTOR signalling that are also involved in sporadic tumours and may even represent potential molecular targets of therapy. In this review, the major characteristics of hereditary tumour syndromes, their molecular genetics and the pathophysiological mechanisms involved in sporadic tumours are discussed. Orv. Hetil., 2013, 154, 1541–1548.
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Furness, John B., and Jeremy J. Cottrell. "Signalling from the gut lumen." Animal Production Science 57, no. 11 (2017): 2175. http://dx.doi.org/10.1071/an17276.
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The lining of the gastrointestinal tract needs to be easily accessible to nutrients and, at the same time, defend against pathogens and chemical challenges. This lining is the largest and most vulnerable surface that faces the outside world. To manage the dual problems of effective nutrient conversion and defence, the gut lining has a sophisticated system for detection of individual chemical entities, pathogenic organisms and their products, and physico-chemical properties of its contents. Detection is through specific receptors that signal to the gut endocrine system, the nervous system, the immune system and local tissue defence systems. These effectors, in turn, modify digestive functions and contribute to tissue defence. Receptors for nutrients include taste receptors for sweet, bitter and savoury, free fatty acid receptors, peptide and phytochemical receptors, that are primarily located on enteroendocrine cells. Hormones released by enteroendocrine cells act locally, through the circulation and via the nervous system, to optimise digestion and mucosal health. Pathogen detection is both through antigen presentation to T-cells and through pattern-recognition receptors (PRRs). Activation of PRRs triggers local tissue defence, for example, by causing release of antimicrobials from Paneth cells. Toxic chemicals, including plant toxins, are sensed and then avoided, expelled or metabolised. It continues to be a major challenge to develop a comprehensive understanding of the integrated responses of the gastrointestinal tract to its luminal contents.
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Guo, SS, X. Wu, AT Shimoide, J. Wong, F. Moatamed, and MP Sawicki. "Frequent overexpression of cyclin D1 in sporadic pancreatic endocrine tumours." Journal of Endocrinology 179, no. 1 (October 1, 2003): 73–79. http://dx.doi.org/10.1677/joe.0.1790073.
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Pancreatic endocrine tumours (PETs) occur sporadically or are inherited as part of the multiple endocrine neoplasia type-1 syndrome. Little is known about the molecular events leading to these tumours. Cyclin D1, a key regulator of the G1/S transition of the cell cycle, is overexpressed in a variety of human cancers as well as certain endocrine tumours. We hypothesized that similar to other endocrine tumours, cyclin D1 is overexpressed in human sporadic PETs. Cyclin D1 protein overexpression was found in 20 of 31 PETs (65%) when compared with normal pancreatic tIssue. Furthermore, Northern blot analysis suggests that cyclin D1 up-regulation occurs at the post-transcriptional level in some PETs. Because the key cell growth signalling pathways p42/p44/ERK (extracellular signal-regulated kinase), p38/MAPK (mitogen-activated protein kinase), and Akt/PKB (protein kinase B) can regulate cyclin D1 protein expression in other cell types, pancreatic endocrine tumours were analysed with phospho-specific antibodies against the active forms of these proteins to elucidate a tIssue-specific regulatory mechanism of cyclin D1 in PETs. We found frequent activation of the p38/MAPK and Akt pathways, but down-regulation of the ERK pathway, in cyclin D1 overexpressing PETs. This study demonstrates that cyclin D1 overexpression is associated with human sporadic PET tumorigenesis, and suggests that this up-regulation may occur at the post-transcriptional level. These findings will direct future studies of PETs towards cell cycle dysregulation and the identification of key growth factor pathways involved in the formation of these tumours.
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Li, Han, Kang Li, Dan Shu, Meiying Shen, Zhaofu Tan, Wenjie Zhang, Dongyao Pu, et al. "MED16 Promotes Tumour Progression and Tamoxifen Sensitivity by Modulating Autophagy through the mTOR Signalling Pathway in ER-Positive Breast Cancer." Life 12, no. 10 (September 20, 2022): 1461. http://dx.doi.org/10.3390/life12101461.
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Recent studies have shown that the mediator complex (MED) plays a vital role in tumorigenesis and development, but the role of MED16 (mediator complex subunit 16) in breast cancer (BC) is not clear. Increasing evidence has shown that the mTOR pathway is important for tumour progression and therapy. In this study, we demonstrated that the mTOR signalling pathway is regulated by the expression level of MED16 in ER+ breast cancer. With the analysis of bioinformatics data and clinical specimens, we revealed an elevated expression of MED16 in luminal subtype tumours. We found that MED16 knockdown significantly inhibited cell proliferation and promoted G1 phase cell cycle arrest in ER+ BC cell lines. Downregulation of MED16 markedly reduced the sensitivity of ER+ BC cells to tamoxifen and increased the stemness and autophagy of ER+ BC cells. Bioinformatic analysis of similar genes to MED16 were mainly enriched in autophagy, endocrine therapy and mTOR signalling pathways, and the inhibition of mTOR-mediated autophagy restored sensitivity to tamoxifen by MED16 downregulation in ER+ BC cells. These results suggest an important role of MED16 in the regulation of tamoxifen sensitivity in ER+ BC cells, crosstalk between the mTOR signalling pathway-induced autophagy, and together, with the exploration of tamoxifen resistance, may indicate a new therapy option for endocrine therapy-resistant patients.
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REES, D. Aled, Maurice F. SCANLON, and Jack HAM. "Novel insights into how purines regulate pituitary cell function." Clinical Science 104, no. 5 (May 1, 2003): 467–81. http://dx.doi.org/10.1042/cs20030053.
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Purine nucleosides and nucleotides are widely distributed substances that exhibit a diverse range of effects in a number of tissues, acting as important extracellular signalling molecules in addition to their more established roles in cellular metabolism. They mediate their effects via activation of distinct cell surface receptors, termed adenosine (or P1) and P2 purinergic receptors. Although roles for adenosine and adenine nucleotides have been described previously in the pituitary gland, the distribution of the receptor subtypes and the effects of their activation on pituitary function are not well defined. Recent evidence, however, has emerged to describe a complex signalling system for purines in the pituitary gland. Data from a variety of studies have shown that the expression pattern, number and affinity of adenosine and/or P2 receptors may be cell-type specific and that non-endocrine in addition to endocrine cells elaborate these receptors. These variations, along with the diverse range of signalling pathways activated, dictate the response of individual cell types to extracellular purines, with roles now emerging for these substances in the regulation of hormone release, pituitary cell proliferation and cytokine/growth factor expression. In this review, we discuss these advances and examine some implications for pituitary growth control and the response of the hypothalamic–pituitary–adrenal axis to stress and inflammation.
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Tataridas-Pallas, Nikolaos, Maximillian A. Thompson, Alexander Howard, Ian Brown, Marina Ezcurra, Ziyun Wu, Isabel Goncalves Silva, et al. "Neuronal SKN-1B modulates nutritional signalling pathways and mitochondrial networks to control satiety." PLOS Genetics 17, no. 3 (March 4, 2021): e1009358. http://dx.doi.org/10.1371/journal.pgen.1009358.
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The feeling of hunger or satiety results from integration of the sensory nervous system with other physiological and metabolic cues. This regulates food intake, maintains homeostasis and prevents disease. In C. elegans, chemosensory neurons sense food and relay information to the rest of the animal via hormones to control food-related behaviour and physiology. Here we identify a new component of this system, SKN-1B which acts as a central food-responsive node, ultimately controlling satiety and metabolic homeostasis. SKN-1B, an ortholog of mammalian NF-E2 related transcription factors (Nrfs), has previously been implicated with metabolism, respiration and the increased lifespan incurred by dietary restriction. Here we show that SKN-1B acts in two hypothalamus-like ASI neurons to sense food, communicate nutritional status to the organism, and control satiety and exploratory behaviours. This is achieved by SKN-1B modulating endocrine signalling pathways (IIS and TGF-β), and by promoting a robust mitochondrial network. Our data suggest a food-sensing and satiety role for mammalian Nrf proteins.
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Planas, A. M., R. Gorina, and Á. Chamorro. "Signalling pathways mediating inflammatory responses in brain ischaemia." Biochemical Society Transactions 34, no. 6 (October 25, 2006): 1267–70. http://dx.doi.org/10.1042/bst0341267.
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Stroke causes neuronal necrosis and generates inflammation. Pro-inflammatory molecules intervene in this process by triggering glial cell activation and leucocyte infiltration to the injured tissue. Cytokines are major mediators of the inflammatory response. Pro-inflammatory and anti-inflammatory cytokines are released in the ischaemic brain. Anti-inflammatory cytokines, such as interleukin-10, promote cell survival, whereas pro-inflammatory cytokines, such as TNFα (tumour necrosis factor α), can induce cell death. However, deleterious effects of certain cytokines can turn to beneficial actions, depending on particular features such as the concentration, time point and the very intricate network of intracellular signals that become activated and interact. A key player in the intracellular response to cytokines is the JAK (Janus kinase)/STAT (signal transducer and activator of transcription) pathway that induces alterations in the pattern of gene transcription. These changes are associated either with cell death or survival depending, among other things, on the specific proteins involved. STAT1 activation is related to cell death, whereas STAT3 activation is often associated with survival. Yet, it is clear that STAT activation must be tightly controlled, and for this reason the function of JAK/STAT modulators, such as SOCS (suppressors of cytokine signalling) and PIAS (protein inhibitor of activated STAT), and phosphatases is most relevant. Besides local effects in the ischaemic brain, cytokines are released to the circulation and affect the immune system. Unbalanced pro-inflammatory and anti-inflammatory plasma cytokine concentrations favouring an ‘anti-inflammatory’ state can decrease the immune response. Robust evidence now supports that stroke can induce an immunodepression syndrome, increasing the risk of infection. The contribution of individual cytokines and their intracellular signalling pathways to this response needs to be further investigated.
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Kapur, R. P., M. D. Gershon, P. J. Milla, and V. Pachnis. "The influence of Hox genes and three intercellular signalling pathways on enteric neuromuscular development." Neurogastroenterology and Motility 16, s1 (April 2004): 8–13. http://dx.doi.org/10.1111/j.1743-3150.2004.00467.x.
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severi, c., i. tattoli, v. d. corleto, m. a. maselli, p. trisolini, and g. delle fave. "Vasoactive intestinal peptide receptor subtypes and signalling pathways involved in relaxation of human stomach." Neurogastroenterology and Motility 18, no. 11 (November 2006): 1009–18. http://dx.doi.org/10.1111/j.1365-2982.2006.00822.x.
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Poitout, A., A. Martinière, B. Kucharczyk, N. Queruel, J. Silva-Andia, S. Mashkoor, L. Gamet, et al. "Local signalling pathways regulate the Arabidopsis root developmental response to Mesorhizobium loti inoculation." Journal of Experimental Botany 68, no. 5 (February 11, 2017): 1199–211. http://dx.doi.org/10.1093/jxb/erw502.
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Wackerhage, Henning, and Aivaras Ratkevicius. "Signal transduction pathways that regulate muscle growth." Essays in Biochemistry 44 (February 1, 2008): 99–108. http://dx.doi.org/10.1042/bse0440099.
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Progressive high-resistance exercise with 8–12 repetitions per set to near failure for beginners and 1–12 repetitions for athletes will increase muscle protein synthesis for up to 72 h; approx. 20 g of protein, especially when ingested directly after exercise, will promote high growth by elevating protein synthesis above breakdown. Muscle growth is regulated by signal transduction pathways that sense and compute local and systemic signals and regulate various cellular functions. The main signalling mechanisms are the phosphorylation of serine, threonine and tyrosine residues by kinases and their dephosphorylation by phosphatases. Muscle growth is stimulated by the mTOR (mammalian target of rapamycin) system, which senses (i) IGF-1 (insulin-like growth factor 1)/MGF (mechano-growth factor)/insulin and/or (ii) mechanical signals, (iii) amino acids and (iv) the energetic state of the muscle, and regulates protein synthesis accordingly. The action of the mTOR system is opposed by myostatin-Smad signalling which inhibits muscle growth via gene transcription.
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Al-Selwi, Yara, James AM Shaw, and Nicole Kattner. "Understanding the Pancreatic Islet Microenvironment in Cystic Fibrosis and the Extrinsic Pathways Leading to Cystic Fibrosis Related Diabetes." Clinical Medicine Insights: Endocrinology and Diabetes 14 (January 2021): 117955142110488. http://dx.doi.org/10.1177/11795514211048813.
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Cystic fibrosis (CF) is an autosomal recessive chronic condition effecting approximately 70 000 to 100 000 people globally and is caused by a loss-of-function mutation in the CF transmembrane conductance regulator. Through improvements in clinical care, life expectancy in CF has increased considerably associated with rising incidence of secondary complications including CF-related diabetes (CFRD). CFRD is believed to result from β-cell loss as well as insufficient insulin secretion due to β-cell dysfunction, but the underlying pathophysiology is not yet fully understood. Here we review the morphological and cellular changes in addition to the architectural remodelling of the pancreatic exocrine and endocrine compartments in CF and CFRD pancreas. We consider also potential underlying proinflammatory signalling pathways impacting on endocrine and specifically β-cell function, concluding that further research focused on these mechanisms may uncover novel therapeutic targets enabling restoration of normal insulin secretion.
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Lawson, Charlotte, Jose M. Vicencio, Derek M. Yellon, and Sean M. Davidson. "Microvesicles and exosomes: new players in metabolic and cardiovascular disease." Journal of Endocrinology 228, no. 2 (February 2016): R57—R71. http://dx.doi.org/10.1530/joe-15-0201.
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The past decade has witnessed an exponential increase in the number of publications referring to extracellular vesicles (EVs). For many years considered to be extracellular debris, EVs are now seen as novel mediators of endocrine signalling via cell-to-cell communication. With the capability of transferring proteins and nucleic acids from one cell to another, they have become an attractive focus of research for different pathological settings and are now regarded as both mediators and biomarkers of disease including cardio-metabolic disease. They also offer therapeutic potential as signalling agents capable of targeting tissues or cells with specific peptides or miRNAs. In this review, we focus on the role that microvesicles (MVs) and exosomes, the two most studied classes of EV, have in diabetes, cardiovascular disease, endothelial dysfunction, coagulopathies, and polycystic ovary syndrome. We also provide an overview of current developments in MV/exosome isolation techniques from plasma and other fluids, comparing different available commercial and non-commercial methods. We describe different techniques for their optical/biochemical characterization and quantitation. We also review the signalling pathways that exosomes and MVs activate in target cells and provide some insight into their use as biomarkers or potential therapeutic agents. In summary, we give an updated focus on the role that these exciting novel nanoparticles offer for the endocrine community.
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Aguilar, Martin, Robert A. Rose, Abhijit Takawale, Stanley Nattel, and Svetlana Reilly. "New aspects of endocrine control of atrial fibrillation and possibilities for clinical translation." Cardiovascular Research 117, no. 7 (March 16, 2021): 1645–61. http://dx.doi.org/10.1093/cvr/cvab080.
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Abstract Hormones are potent endo-, para-, and autocrine endogenous regulators of the function of multiple organs, including the heart. Endocrine dysfunction promotes a number of cardiovascular diseases, including atrial fibrillation (AF). While the heart is a target for endocrine regulation, it is also an active endocrine organ itself, secreting a number of important bioactive hormones that convey significant endocrine effects, but also through para-/autocrine actions, actively participate in cardiac self-regulation. The hormones regulating heart-function work in concert to support myocardial performance. AF is a serious clinical problem associated with increased morbidity and mortality, mainly due to stroke and heart failure. Current therapies for AF remain inadequate. AF is characterized by altered atrial function and structure, including electrical and profibrotic remodelling in the atria and ventricles, which facilitates AF progression and hampers its treatment. Although features of this remodelling are well-established and its mechanisms are partly understood, important pathways pertinent to AF arrhythmogenesis are still unidentified. The discovery of these missing pathways has the potential to lead to therapeutic breakthroughs. Endocrine dysfunction is well-recognized to lead to AF. In this review, we discuss endocrine and cardiocrine signalling systems that directly, or as a consequence of an underlying cardiac pathology, contribute to AF pathogenesis. More specifically, we consider the roles of products from the hypothalamic-pituitary axis, the adrenal glands, adipose tissue, the renin–angiotensin system, atrial cardiomyocytes, and the thyroid gland in controlling atrial electrical and structural properties. The influence of endocrine/paracrine dysfunction on AF risk and mechanisms is evaluated and discussed. We focus on the most recent findings and reflect on the potential of translating them into clinical application.
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Creta, Massimiliano, Giuseppe Celentano, Luigi Napolitano, Roberto La Rocca, Marco Capece, Gianluigi Califano, Claudia Collà Ruvolo, et al. "Inhibition of Androgen Signalling Improves the Outcomes of Therapies for Bladder Cancer: Results from a Systematic Review of Preclinical and Clinical Evidence and Meta-Analysis of Clinical Studies." Diagnostics 11, no. 2 (February 20, 2021): 351. http://dx.doi.org/10.3390/diagnostics11020351.
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Bladder cancer (BCa) is an endocrine-related tumour and the activation of androgen signalling pathways may promote bladder tumorigenesis. We summarized the available preclinical and clinical evidence on the implications of the manipulation of androgen signalling pathways on the outcomes of BCa therapies. A systematic review was performed in December 2020. We included papers that met the following criteria: original preclinical and clinical research; evaluating the impact of androgen signalling modulation on the outcomes of BCa therapies. Six preclinical and eight clinical studies were identified. The preclinical evidence demonstrates that the modulation of androgen receptor-related pathways has the potential to interfere with the activity of the Bacillus Calmette Guerin, doxorubicin, cisplatin, gemcitabine, and radiotherapy. The relative risk of BCa recurrence after transurethral resection of the bladder tumour (TURBT) is significantly lower in patients undergoing therapy with 5 alpha reductase inhibitors (5-ARIs) or androgen deprivation therapy (ADT) (Relative risk: 0.50, 95% CI: 0.30–0.82; p = 0.006). Subgroup analysis in patients receiving 5-ARIs revealed a relative risk of BCa recurrence of 0.46 (95% CI: 0.22–0.95; p = 0.040). A significant negative association between the ratio of T1 BCa patients in treated/control groups and the relative risk of BCa recurrence was observed. Therapy with 5-ARIs may represent a potential strategy aimed at reducing BCa recurrence rate, mainly in patients with low stage disease. Further studies are needed to confirm these preliminary data.
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Mani, S. K., W. Portillo, and A. Reyna. "Steroid Hormone Action in the Brain: Cross-Talk Between Signalling Pathways." Journal of Neuroendocrinology 21, no. 4 (April 2009): 243–47. http://dx.doi.org/10.1111/j.1365-2826.2009.01844.x.
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García-Ferrés, Mar, Carlos Sánchez-Higueras, Jose Manuel Espinosa-Vázquez, and James C-G Hombría. "Specification of the endocrine primordia controlling insect moulting and metamorphosis by the JAK/STAT signalling pathway." PLOS Genetics 18, no. 10 (October 3, 2022): e1010427. http://dx.doi.org/10.1371/journal.pgen.1010427.
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The corpora allata and the prothoracic glands control moulting and metamorphosis in insects. These endocrine glands are specified in the maxillary and labial segments at positions homologous to those forming the trachea in more posterior segments. Glands and trachea can be homeotically transformed into each other suggesting that all three evolved from a metamerically repeated organ that diverged to form glands in the head and respiratory organs in the trunk. While much is known about tracheal specification, there is limited information about corpora allata and prothorathic gland specification. Here we show that the expression of a key regulator of early gland development, the snail gene, is controlled by the Dfd and Scr Hox genes and by the Hedgehog and Wnt signalling pathways that induce localised transcription of upd, the ligand of the JAK/STAT signalling pathway, which lies at the heart of gland specification. Our results show that the same upstream regulators are required for the early gland and tracheal primordia specification, reinforcing the hypothesis that they originated from a segmentally repeated organ present in an ancient arthropod.
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Sominsky, L., A. P. Sobinoff, V. Pye, E. A. McLaughlin, and D. M. Hodgson. "10. Modulation of inflammatory signalling pathways in the ovary by immune challenge in early life." Brain, Behavior, and Immunity 32 (September 2013): e3. http://dx.doi.org/10.1016/j.bbi.2013.07.022.
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Brisken, Cathrin, Kathryn Hess, and Rachel Jeitziner. "Progesterone and Overlooked Endocrine Pathways in Breast Cancer Pathogenesis." Endocrinology 156, no. 10 (August 4, 2015): 3442–50. http://dx.doi.org/10.1210/en.2015-1392.
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Worldwide, breast cancer incidence has been increasing for decades. Exposure to reproductive hormones, as occurs with recurrent menstrual cycles, affects breast cancer risk, and can promote disease progression. Exogenous hormones and endocrine disruptors have also been implicated in increasing breast cancer incidence. Numerous in vitro studies with hormone-receptor-positive cell lines have provided insights into the complexities of hormone receptor signaling at the molecular level; in vivo additional layers of complexity add on to this. The combined use of mouse genetics and tissue recombination techniques has made it possible to disentangle hormone action in vivo and revealed that estrogens, progesterone, and prolactin orchestrate distinct developmental stages of mammary gland development. The 2 ovarian steroids that fluctuate during menstrual cycles act on a subset of mammary epithelial cells, the hormone-receptor-positive sensor cells, which translate and amplify the incoming systemic signals into local, paracrine stimuli. Progesterone has emerged as a major regulator of cell proliferation and stem cell activation in the adult mammary gland. Two progesterone receptor targets, receptor activator of NfκB ligand and Wnt4, serve as downstream paracrine mediators of progesterone receptor-induced cell proliferation and stem cell activation, respectively. Some of the findings in the mouse have been validated in human ex vivo models and by next-generation whole-transcriptome sequencing on healthy donors staged for their menstrual cycles. The implications of these insights into the basic control mechanisms of mammary gland development for breast carcinogenesis and the possible role of endocrine disruptors, in particular bisphenol A in this context, will be discussed below.
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Reilly, Jamie, Louise Gallagher, Geraldine Leader, and Sanbing Shen. "Coupling of autism genes to tissue-wide expression and dysfunction of synapse, calcium signalling and transcriptional regulation." PLOS ONE 15, no. 12 (December 18, 2020): e0242773. http://dx.doi.org/10.1371/journal.pone.0242773.
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Autism Spectrum Disorder (ASD) is a heterogeneous disorder that is often accompanied with many co-morbidities. Recent genetic studies have identified various pathways from hundreds of candidate risk genes with varying levels of association to ASD. However, it is unknown which pathways are specific to the core symptoms or which are shared by the co-morbidities. We hypothesised that critical ASD candidates should appear widely across different scoring systems, and that comorbidity pathways should be constituted by genes expressed in the relevant tissues. We analysed the Simons Foundation for Autism Research Initiative (SFARI) database and four independently published scoring systems and identified 292 overlapping genes. We examined their mRNA expression using the Genotype-Tissue Expression (GTEx) database and validated protein expression levels using the human protein atlas (HPA) dataset. This led to clustering of the overlapping ASD genes into 2 groups; one with 91 genes primarily expressed in the central nervous system (CNS geneset) and another with 201 genes expressed in both CNS and peripheral tissues (CNS+PT geneset). Bioinformatic analyses showed a high enrichment of CNS development and synaptic transmission in the CNS geneset, and an enrichment of synapse, chromatin remodelling, gene regulation and endocrine signalling in the CNS+PT geneset. Calcium signalling and the glutamatergic synapse were found to be highly interconnected among pathways in the combined geneset. Our analyses demonstrate that 2/3 of ASD genes are expressed beyond the brain, which may impact peripheral function and involve in ASD co-morbidities, and relevant pathways may be explored for the treatment of ASD co-morbidities.
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McKeen, Hayley D., Donal J. Brennan, Shauna Hegarty, Fiona Lanigan, Karin Jirstrom, Christopher Byrne, Anita Yakkundi, Helen O. McCarthy, William M. Gallagher, and Tracy Robson. "The emerging role of FK506-binding proteins as cancer biomarkers: a focus on FKBPL." Biochemical Society Transactions 39, no. 2 (March 22, 2011): 663–68. http://dx.doi.org/10.1042/bst0390663.
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FKBPs (FK506-binding proteins) have long been recognized as key regulators of the response to immunosuppressant drugs and as co-chaperones of steroid receptor complexes. More recently, evidence has emerged suggesting that this diverse protein family may also represent cancer biomarkers owing to their roles in cancer progression and response to treatment. FKBPL (FKBP-like) is a novel FKBP with roles in GR (glucocorticoid receptor), AR (androgen receptor) and ER (oestrogen receptor) signalling. FKBPL binds Hsp90 (heat-shock protein 90) and modulates translocation, transcriptional activation and phosphorylation of these steroid receptors. It has been proposed as a novel prognostic and predictive biomarker, where high levels predict for increased recurrence-free survival in breast cancer patients and enhanced sensitivity to endocrine therapy. Since this protein family has roles in a plethora of signalling pathways, its members represent novel prognostic markers and therapeutic targets for cancer diagnosis and treatment.
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Hastings, Michael, John S. O’Neill, and Elizabeth S. Maywood. "Circadian clocks: regulators of endocrine and metabolic rhythms." Journal of Endocrinology 195, no. 2 (November 2007): 187–98. http://dx.doi.org/10.1677/joe-07-0378.
Full textAbstract:
Daily and seasonal rhythms in the endocrine system are co-ordinated by a hypothalamic pacemaker, the suprachiasmatic nuclei (SCN) that is synchronised to solar time by direct retinal afferents. Individual SCN neurons are circadian clocks, their intrinsic oscillator consisting of a series of interlinked autoregulatory transcriptional/post-translational feedback loops incorporating Period (Per) and Cryptochrome (Cry) genes. Mutations that alter the rate of transcription of Per and Cry genes or the stability of Per and Cry proteins affect clock speed. Molecular timekeeping in SCN neurons is synchronised and sustained by interneuronal neuropeptidergic signals. A molecular clock mechanism comparable to that of the SCN is present in most major organ systems. These tissue clocks are synchronised by endocrine, autonomic and behavioural cues that are dependent on the SCN, and in turn they drive the circadian expression of local transcriptomes, thereby co-ordinating circadian metabolism and physiology. Rhythmic glucocorticoid signalling is a prominent mediator of SCN output and internal synchroniser. The role of local SCN-synchronised clocks in controlling vital processes, including xenobiotic detoxification, cell division and nutrient metabolism, is essential to health, and disturbances to circadian timing arising from modern working schedules are becoming recognised as an increasingly relevant factor in major systemic illness. Moreover, the newly identified molecular components of circadian control systems provide novel avenues for therapeutic intervention.