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1.
Toxicology ; 505: 153846, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38815618

RESUMO

Atrazine (ATR) is one of the most widely utilized herbicides globally and is prevalent in the environment due to its extensive use and long half-life. It can infiltrate the human body through drinking water, ingestion, and dermal contact, and has been recognized as an environmental endocrine disruptor. This study aims to comprehensively outline the detrimental impacts of ATR on the endocrine system. Previous research indicates that ATR is harmful to various bodily systems, including the reproductive system, nervous system, adrenal glands, and thyroi d gland. The toxic effects of ATR on the endocrine system and its underlying molecular mechanisms are summarized as follows: influencing the expression of kisspeptin in the HPG axis, consequently affecting steroid synthesis; disrupting DNA synthesis and meiosis, as well as modifying DNA methylation levels, leading to reproductive and developmental toxicity; impacting dopamine by altering Nurr1, VMAT2, and DAT expression, consequently affecting dopamine synthesis and transporter expression, and influencing other neurotransmitters, resulting in neurotoxicity; and changing adipose tissue synthesis and metabolism by reducing basal metabolism, impairing cellular oxidative phosphorylation, and inducing insulin resistance. Additionally, a compilation of natural products used to mitigate the toxic effects of ATR has been provided, encompassing melatonin, curcumin, quercetin, lycopene, flavonoids, vitamin C, vitamin E, and other natural remedies. It is important to note that existing research predominantly relies on in vitro and ex vivo experiments, with limited population-based empirical evidence available.


Assuntos
Atrazina , Disruptores Endócrinos , Herbicidas , Atrazina/toxicidade , Humanos , Animais , Disruptores Endócrinos/toxicidade , Herbicidas/toxicidade , Sistema Endócrino/efeitos dos fármacos
2.
Arch Toxicol ; 98(7): 2019-2045, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38704806

RESUMO

For endocrine disrupting chemicals (EDC) the existence of "safe exposure levels", that is exposure levels that do not present an appreciable risk to human health is most controversially discussed, as is the existence of health-based reference values. Concerns have been especially raised that EDCs might not possess a threshold level such that no exposure level to EDCs can be considered safe. To explore whether or not threshold levels can be identified, we performed a screening exercise on 14 pesticidal and biocidal active substances previously identified as EDCs in the European Union. The respective substances are ideal subjects for case studies to review for endocrine activity and disruptive potential following well-defined regulatory assessment based on solid data to effectually establish adversity as consequence of endocrine disruption. Dimethomorph, metiram and propiconazole for which the weight of evidence demonstrating endocrine disruption was the strongest were used as subjects for further study. Epoxiconazole was additionally selected as its effects on the endocrine system are extensive. For all four substances, analysis of the toxicological data clearly indicated thresholds of adversity below which no adverse effects mediated through an endocrine mechanism were observed. Particular emphasis was placed on mechanistic considerations including homeostasis and the concept of adversity. As a proof of concept this study provides evidence that like other substances of toxicological concern EDCs have threshold levels for adversity. While for some EDCs the respective thresholds might indeed be very low this shows that, data allowing, for other EDCs sufficiently protective reference values can be derived.


Assuntos
Disruptores Endócrinos , Disruptores Endócrinos/toxicidade , Humanos , Medição de Risco , Animais , Praguicidas/toxicidade , Exposição Ambiental/efeitos adversos , Triazóis/toxicidade , União Europeia , Nível de Efeito Adverso não Observado , Sistema Endócrino/efeitos dos fármacos , Compostos de Epóxi/toxicidade
3.
World J Gastroenterol ; 30(9): 1073-1095, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38577191

RESUMO

Hepatocrinology explores the intricate relationship between liver function and the endocrine system. Chronic liver diseases such as liver cirrhosis can cause endocrine disorders due to toxin accumulation and protein synthesis disruption. Despite its importance, assessing endocrine issues in cirrhotic patients is frequently neglected. This article provides a comprehensive review of the epidemiology, pathophysiology, diagnosis, and treatment of endocrine disturbances in liver cirrhosis. The review was conducted using the PubMed/Medline, EMBASE, and Scielo databases, encompassing 172 articles. Liver cirrhosis is associated with endocrine disturbances, including diabetes, hypoglycemia, sarcopenia, thyroid dysfunction, hypogonadotropic hypogonadism, bone disease, adrenal insufficiency, growth hormone dysfunction, and secondary hyperaldosteronism. The optimal tools for diagnosing diabetes and detecting hypoglycemia are the oral glucose tolerance test and continuous glucose monitoring system, respectively. Sarcopenia can be assessed through imaging and functional tests, while other endocrine disorders are evaluated using hormonal assays and imaging studies. Treatment options include metformin, glucagon-like peptide-1 analogs, sodium-glucose co-transporter-2 inhibitors, and insulin, which are effective and safe for diabetes control. Established standards are followed for managing hypoglycemia, and hormone replacement therapy is often necessary for other endocrine dysfunctions. Liver transplantation can address some of these problems.


Assuntos
Diabetes Mellitus , Hipoglicemia , Sarcopenia , Humanos , Automonitorização da Glicemia , Sarcopenia/diagnóstico , Sarcopenia/etiologia , Sarcopenia/terapia , Glicemia/metabolismo , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/terapia , Sistema Endócrino/metabolismo , Diabetes Mellitus/epidemiologia , Insulina/uso terapêutico , Hipoglicemia/complicações
5.
Int J Mol Sci ; 25(7)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38612627

RESUMO

The aryl hydrocarbon receptor (AHR) serves as a ligand-activated transcription factor crucial for regulating fundamental cellular and molecular processes, such as xenobiotic metabolism, immune responses, and cancer development. Notably, a spectrum of endocrine-disrupting chemicals (EDCs) act as agonists or antagonists of AHR, leading to the dysregulation of pivotal cellular and molecular processes and endocrine system disruption. Accumulating evidence suggests a correlation between EDC exposure and the onset of diverse pancreatic diseases, including diabetes, pancreatitis, and pancreatic cancer. Despite this association, the mechanistic role of AHR as a linchpin molecule in EDC exposure-related pathogenesis of pancreatic diseases and cancer remains unexplored. This review comprehensively examines the involvement of AHR in EDC exposure-mediated regulation of pancreatic pathogenesis, emphasizing AHR as a potential therapeutic target for the pathogenesis of pancreatic diseases and cancer.


Assuntos
Pancreatopatias , Neoplasias Pancreáticas , Pancreatite , Humanos , Receptores de Hidrocarboneto Arílico/genética , Pancreatopatias/etiologia , Neoplasias Pancreáticas/etiologia , Pancreatite/induzido quimicamente , Sistema Endócrino
6.
Environ Toxicol Pharmacol ; 107: 104435, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38588759

RESUMO

This study investigated the impact of neonatal exposure to endocrine-active compounds (EACs): flutamide (antiandrogen), 4-tert-octylphenol (an estrogenic compound), and methoxychlor (an organochlorine insecticide exhibiting estrogenic, antiestrogenic and antiandrogenic activities) on androgen production within porcine adrenal glands. The expression of genes related to androgen synthesis and the level of androgen production were analyzed (i) in the adrenal glands of piglets exposed to EACs during the first 10 days of life (in vivo study), and (ii) in adrenal explants from sow-fed or formula-fed 10-day-old piglets incubated with EACs (ex vivo study). EACs affected the expression of genes linked to adrenal androgen biosynthesis. The prominent effect of methoxychlor on downregulation of StAR, CYP11A1 and HSD3B and upregulation of CYP17A1 and SULT2A1 were demonstrated. Furthermore, our study revealed divergent response to EACs between sow-fed and formula-fed piglets, suggesting that natural feeding may provide protection against adverse EACs effects, particularly those interfering with estrogens action.


Assuntos
Androgênios , Metoxicloro , Animais , Feminino , Suínos , Metoxicloro/metabolismo , Sistema Endócrino , Estrogênios , Antagonistas de Androgênios/toxicidade
7.
Horm Behav ; 161: 105529, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38492501

RESUMO

Central to the navigation of an ever-changing environment is the ability to form positive associations with places and conspecifics. The functions of location and social conditioned preferences are often studied independently, limiting our understanding of their interplay. Furthermore, a de-emphasis on natural functions of conditioned preferences has led to neurobiological interpretations separated from ecological context. By adopting a naturalistic and ethological perspective, we uncover complexities underlying the expression of conditioned preferences. Development of conditioned preferences is a combination of motivation, reward, associative learning, and context, including for social and spatial environments. Both social- and location-dependent reward-responsive behaviors and their conditioning rely on internal state-gating mechanisms that include neuroendocrine and hormone systems such as opioids, dopamine, testosterone, estradiol, and oxytocin. Such reinforced behavior emerges from mechanisms integrating past experience and current social and environmental conditions. Moreover, social context, environmental stimuli, and internal state gate and modulate motivation and learning via associative reward, shaping the conditioning process. We highlight research incorporating these concepts, focusing on the integration of social neuroendocrine mechanisms and behavioral conditioning. We explore three paradigms: 1) conditioned place preference, 2) conditioned social preference, and 3) social conditioned place preference. We highlight nonclassical species to emphasize the naturalistic applications of these conditioned preferences. To fully appreciate the complex integration of spatial and social information, future research must identify neural networks where endocrine systems exert influence on such behaviors. Such research promises to provide valuable insights into conditioned preferences within a broader naturalistic context.


Assuntos
Recompensa , Animais , Motivação/fisiologia , Humanos , Sistema Endócrino/fisiologia , Comportamento Social , Condicionamento Psicológico/fisiologia , Aprendizagem por Associação/fisiologia
9.
Nat Rev Endocrinol ; 20(7): 414-425, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38514815

RESUMO

The acid-labile subunit (ALS) of the insulin-like growth factor (IGF) binding protein (IGFBP) complex, encoded in humans by IGFALS, has a vital role in regulating the endocrine transport and bioavailability of IGF-1 and IGF-2. Accordingly, ALS has a considerable influence on postnatal growth and metabolism. ALS is a leucine-rich glycoprotein that forms high-affinity ternary complexes with IGFBP-3 or IGFBP-5 when they are occupied by either IGF-1 or IGF-2. These complexes constitute a stable reservoir of circulating IGFs, blocking the potentially hypoglycaemic activity of unbound IGFs. ALS is primarily synthesized by hepatocytes and its expression is lower in non-hepatic tissues. ALS synthesis is strongly induced by growth hormone and suppressed by IL-1ß, thus potentially serving as a marker of growth hormone secretion and/or activity and of inflammation. IGFALS mutations in humans and Igfals deletion in mice cause modest growth retardation and pubertal delay, accompanied by decreased osteogenesis and enhanced adipogenesis. In hepatocellular carcinoma, IGFALS is described as a tumour suppressor; however, its contribution to other cancers is not well delineated. This Review addresses the endocrine physiology and pathology of ALS, discusses the latest cell and proteomic studies that suggest emerging cellular roles for ALS and outlines its involvement in other disease states.


Assuntos
Glicoproteínas , Humanos , Animais , Glicoproteínas/metabolismo , Proteínas de Transporte/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Camundongos , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/metabolismo , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/fisiologia , Fator de Crescimento Insulin-Like II/metabolismo , Sistema Endócrino/metabolismo , Peptídeos Semelhantes à Insulina
11.
J Hazard Mater ; 469: 133778, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38460255

RESUMO

Information on the indoor environment as a source of exposure with potential adverse health effects is mostly limited to a few pollutant groups and indoor types. This study provides a comprehensive toxicological profile of chemical mixtures associated with dust from various types of indoor environments, namely cars, houses, prefabricated apartments, kindergartens, offices, public spaces, and schools. Organic extracts of two different polarities and bioaccessible extracts mimicking the gastrointestinal conditions were prepared from two different particle size fractions of dust. These extracts were tested on a battery of human cell-based bioassays to assess endocrine disrupting potentials. Furthermore, 155 chemicals from different pollutant groups were measured and their relevance for the bioactivity was determined using concentration addition modelling. The exhaustive and bioaccessible extracts of dust from the different microenvironments interfered with aryl hydrocarbon receptor, estrogen, androgen, glucocorticoid, and thyroid hormone (TH) receptor signalling, and with TH transport. Noteably, bioaccessible extracts from offices and public spaces showed higher estrogenic effects than the organic solvent extracts. 114 of the 155 targeted chemicals were detectable, but the observed bioactivity could be only marginally explained by the detected chemicals. Diverse toxicity patterns across different microenvironments that people inhabit throughout their lifetime indicate potential health and developmental risks, especially for children. Limited data on the endocrine disrupting potency of relevant chemical classes, especially those deployed as replacements for legacy contaminants, requires further study.


Assuntos
Poluição do Ar em Ambientes Fechados , Poluentes Ambientais , Criança , Humanos , Poeira/análise , Sistema Endócrino , Estrogênios , Androgênios , Poluição do Ar em Ambientes Fechados/análise
12.
J Hazard Mater ; 469: 134108, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38521039

RESUMO

Numerous pesticides pose a threat to aquatic ecosystems, jeopardizing aquatic animal species and impacting human health. While the contamination of aquatic environment by flutolanil and its adverse effects on animal in the treatment of rich sheath blight have been reported, the neuro-visual effects of flutolanil at environmentally relevant concentrations remain unknown. In this study, we administered flutolanil to zebrafish embryos (0, 0.125, 0.50 and 2.0 mg/L) for 4 days to investigate its impact on the neuro and visual system. The results revealed that flutolanil induced abnormal behavior in larvae, affecting locomotor activity, stimuli response and phototactic response. Additionally, it led to defective brain and ocular development and differentiation. The disruption extended to the neurological system and visual phototransduction of larvae, evidenced by significant disturbances in genes and proteins related to neurodevelopment, neurotransmission, eye development, and visual function. Untargeted metabolomics analysis revealed that the GABAergic signaling pathway and increased levels of glutamine, glutamate, andγ-aminobutyric acid were implicated in the response to neuro and visual system injury induced by flutolanil, contributing to aberrant development, behavioral issues, and endocrine disruption. This study highlights the neuro-visual injury caused by flutolanil in aquatic environment, offering fresh insights into the mechanisms underlying image and non-image effects.


Assuntos
Anilidas , Poluentes Químicos da Água , Peixe-Zebra , Animais , Humanos , Peixe-Zebra/metabolismo , Larva , Ecossistema , Sistema Endócrino , Poluentes Químicos da Água/metabolismo
13.
Mol Cell Endocrinol ; 587: 112211, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38494046

RESUMO

The endocrine system plays a pivotal role in shaping the mechanisms that ensure successful reproduction. With over a million known insect species, understanding the endocrine control of reproduction has become increasingly complex. Some of the key players include the classic insect lipid hormones juvenile hormone (JH) and ecdysteroids, and neuropeptides such as insulin-like peptides (ILPs). Individual endocrine factors not only modulate their own target tissue but also play crucial roles in crosstalk among themselves, ensuring successful vitellogenesis and oogenesis. Recent advances in omics, gene silencing, and genome editing approaches have accelerated research, offering both fundamental insights and practical applications for studying in-depth endocrine signaling pathways. This review provides an updated and integrated view of endocrine factors modulating vitellogenesis and oogenesis in insect females.


Assuntos
Oogênese , Vitelogênese , Animais , Feminino , Insetos , Hormônios Juvenis/metabolismo , Sistema Endócrino/metabolismo
14.
Artigo em Inglês | MEDLINE | ID: mdl-38460577

RESUMO

Estrogens and androgens are typical steroid hormones and often occur together in contaminated aquatic environments, but their mixed effects in aquatic organisms have been less well reported. In this study, the endocrine disrupting effects of binary mixtures of 17ß-estradiol (E2) and testosterone (T) in western mosquitofish (Gambusia affinis) were assessed by analyzing the sex ratio, secondary sex characteristics, gonadal histology, and transcriptional expression of target genes related to the hypothalamic-pituitary-gonadal (HPG) axis in G. affinis (from embryos) continuously exposed to E2 (50 ng/L), T (T1: 50 ng/L; T2: 200 ng/L), and mixtures of both (E2 + T1: 50 + 50 ng/L; E2 + T2: 50 + 200 ng/L) for 119 d. The results showed that exposure to E2 + T1 and E2 + T2 reduced the length ratio of ray 4/6 ratio in male G. affinis, suggesting feminized phenomenon in male G. affinis. Furthermore, 16.7-38.5 % of female G. affinis showed masculinized anal fins and hemal spines when exposed to T alone and in combination with E2. Importantly, the transcriptional levels of certain target genes related to the HPG axis were significantly altered in G. affinis following exposure to E2 and T alone and in combinations. Moreover, exposure to E2 and T in combinations can lead to combined effects (such as synergistic and antagonistic effects) on the transcriptional levels of some genes. These results collectively suggest that exposure to environmentally relevant concentrations of E2 and T alone and in mixtures can impact the endocrine system of G. affinis, and may pose potential risks in aquatic systems.


Assuntos
Ciprinodontiformes , Poluentes Químicos da Água , Masculino , Feminino , Animais , Testosterona/metabolismo , Estradiol/metabolismo , Androgênios/toxicidade , Sistema Endócrino , Ciprinodontiformes/genética , Ciprinodontiformes/metabolismo , Poluentes Químicos da Água/metabolismo
15.
Gen Comp Endocrinol ; 351: 114481, 2024 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-38408711

RESUMO

The pituitary gland is a small endocrine gland located below the hypothalamus. This gland releases several important hormones and controls the function of many other endocrine system glands to release hormones. Fish pituitary hormonal cells are controlled by neuroendocrine and sex steroid feedback. To study the complex pituitary function in vivo, we established an in vitro pituitary spheroid assay and evaluated its suitability for monitoring the annual reproductive physiological conditions in Takifugu rubripes, also known as torafugu, is one of the most economically important species distributed in the northwestern part of the Pacific Ocean, in the western part of the East China Sea, and in more northern areas near Hokkaido, Japan. Fish pituitary spheroids can be easily constructed in liquid or solid plates. The culture medium (L-15) made the aggregation faster than MEM (Hank's). A Rho-kinase inhibitor (Y-27632, 10 µM) and/or fish serum (2.5 %) also promoted spheroid formation. Laser confocal microscopy analysis of spheroids cultured with annual serum of both sexes revealed that luteinizing hormone (LH) synthesis has the highest peak in the final maturation stage (3 years old, May) in accordance with the highest serum sex steroid levels; in contrast, follicle stimulating hormone (FSH) synthesis has no correlation with the dose of serum or nutrients. Similarly, 3D cell propagation assays using female serum showed that total pituitary cells displayed the highest proliferation at puberty onset (2 years old, October) before half a year of the spawning season. These results indicate that pituitary spheroids are useful in vitro models for monitoring the reproductive physiological status of fish in vivo and may be applicable to the in vitro screening of environmental chemicals and bioactive compounds affecting reproductive efficiency in aquaculture.


Assuntos
Hipófise , Maturidade Sexual , Animais , Masculino , Feminino , Hormônio Luteinizante , Hormônio Foliculoestimulante , Sistema Endócrino , Hormônios Esteroides Gonadais , Esteroides , Hormônio Liberador de Gonadotropina/fisiologia
16.
Cell Tissue Res ; 396(2): 197-212, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38369645

RESUMO

The natriuretic peptide (NP) family consists of cardiac NPs (ANP, BNP, and VNP) and brain NPs (CNPs) in teleosts. In addition to CNP1-4, a paralogue of CNP4 (named CNP4b) was recently discovered in basal teleosts including Japanese eel. Mammals have lost most Cnps during the evolution, but teleost cnps were conserved and diversified, suggesting that CNPs are important hormones for maintaining brain functions in teleost. The present study evaluated the potency of each Japanese eel CNP to their NP receptors (NPR-A, NPR-B, NPR-C, and NPR-D) overexpressed in CHO cells. A comprehensive brain map of cnps- and nprs-expressing neurons in Japanese eel was constructed by integrating the localization results obtained by in situ hybridization. The result showed that CHO cells expressing NPR-A and NPR-B induced strong cGMP productions after stimulation by cardiac and brain NPs, respectively. Regarding brain distribution of cnps, cnp1 is engaged in the ventral telencephalic area and periventricular area including the parvocellular preoptic nucleus (Pp), anterior/posterior tuberal nuclei, and periventricular gray zone of the optic tectum. cnp3 is found in the habenular nucleus and prolactin cells in the pituitary. cnp4 is expressed in the ventral telencephalic area, while cnp4b is expressed in the motoneurons in the medullary area. Such CNP isoform-specific localizations suggest that function of each CNP has diverged in the eel brain. Furthermore, the Pp lacking the blood-brain barrier expressed both npra and nprb, suggesting that endocrine and paracrine NPs interplay for regulating the Pp functions in Japanese eels.


Assuntos
Encéfalo , Cricetulus , Peptídeos Natriuréticos , Animais , Encéfalo/metabolismo , Peptídeos Natriuréticos/metabolismo , Células CHO , Receptores do Fator Natriurético Atrial/metabolismo , Comunicação Parácrina , Ligantes , Anguilla/metabolismo , Sistema Endócrino/metabolismo
17.
Mol Cell Endocrinol ; 585: 112189, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38365065

RESUMO

A significant advance has been made, especially during the last two decades, in the knowledge of the effects on crustacean species of pollutants proven to be endocrine disruptors in vertebrates. Such effects have been also interpreted in the light of recent studies on crustacean endocrinology. Year after year, the increased number of reports refer to the effects of endocrine disruptors on several processes hormonally controlled. This review is aimed at summarizing and discussing the effects of several kinds of endocrine disruptors on the hormonal control of reproduction (including gonadal growth, sexual differentiation, and offspring development), molting, and intermediate metabolism of crustaceans. A final discussion about the state of the art, as well as the perspective of this toxicological research line is given.


Assuntos
Disruptores Endócrinos , Poluentes Ambientais , Animais , Disruptores Endócrinos/toxicidade , Sistema Endócrino , Crustáceos , Reprodução , Poluentes Ambientais/farmacologia
18.
Front Endocrinol (Lausanne) ; 15: 1340432, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38318293

RESUMO

Introduction: Hormones play a vital role in development from conception to birth and throughout the human lifespan. These periods are logically divided into fetal development, pre-pubertal growth, puberty, and adulthood. Deviations from standard physiological levels and release patterns of constituent hormones can lead to pathology affecting the normal developmental trajectory. Research is ongoing to better understand the mechanisms of these hormones and how their modulation affects development. Methods: This article focuses on recent developments in understanding the role hormones play in development. We also cover recent discoveries in signaling pathways and hormonal regulation. Results: New and continuing research into functional hormone regulation focuses on sex hormones, gonadotropic hormones, growth hormones, insulin-like growth factor, thyroid hormone, and the interconnectedness of each of these functional axes. Currently, the abundance of work focuses on fertility and correction of sex hormone levels based on an individual's condition and stage in life. Discussion: Continuing research is needed to fully understand the long-term effects of hormone modulation in growth and sexual development. The role of each hormone in parallel endocrine axes should also be more thoroughly investigated to help improve the safety and efficacy in endocrine pharmacotherapeutics.


Assuntos
Hormônios Esteroides Gonadais , Hormônio do Crescimento , Humanos , Hormônios Esteroides Gonadais/fisiologia , Hormônio do Crescimento/fisiologia , Sistema Endócrino , Gonadotropinas , Hormônios Tireóideos
19.
Biomed Pharmacother ; 172: 116218, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38308969

RESUMO

Microbial metabolites have been indicated to communicate with the host's endocrine system, regulating hormone production, immune-endocrine communications, and interactions along the gut-brain axis, eventually affecting the occurrence of endocrine cancer. Furthermore, microbiota metabolites such as short-chain fatty acids (SCFAs) have been found to affect the tumor microenvironment and boost immunity against tumors. SCFAs, including butyrate and acetate, have been demonstrated to exert anti-proliferative and anti-protective activity on pancreatic cancer cells. The employing of microbial metabolic products in conjunction with radiation and chemotherapy has shown promising outcomes in terms of reducing treatment side effects and boosting effectiveness. Certain metabolites, such as valerate and butyrate, have been made known to improve the efficiency of CAR T-cell treatment, whilst others, such as indole-derived tryptophan metabolites, have been shown to inhibit tumor immunity. This review explores the intricate interplay between microbial metabolites and endocrine tumorigenesis, spanning mechanistic insights to the discovery of potential therapeutic biomarkers.


Assuntos
Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/fisiologia , Ácidos Graxos Voláteis/metabolismo , Butiratos , Biomarcadores , Carcinogênese , Sistema Endócrino , Microambiente Tumoral
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