The Role of Endocrine Disruption Chemical-Regulated Aryl Hydrocarbon Receptor Activity in the Pathogenesis of Pancreatic Diseases and Cancer.

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.

From liver to hormones: The endocrine consequences of cirrhosis.

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.

Impact of endocrine-active compounds on adrenal androgen production in pigs during neonatal period.

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.

Combined effects of binary mixtures of 17ß-estradiol and testosterone in western mosquitofish (Gambusia affinis) after full life-cycle exposure.

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.

Endocrine factors modulating vitellogenesis and oogenesis in insects: An update.

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.

Endocrine disrupting potential of total and bioaccessible extracts of dust from seven different types of indoor environment.

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.

Exposure to flutolanil at environmentally relevant concentrations can induce image and non-image-forming failure of zebrafish larvae through neuro and visual disruptions.

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.

Cuidado ás pessoas com agravos endocrinos e metabólicos / Care for people with endocrine and metabolic problems

O objetivo desse trabalho é descrever a sistematização da Assistência de Enfermagem a pessoas com agravos endócrinos e metabólicos pautado na teoria de Calista Roy. Metodologia: Trata-se de um relato de experiência através da aplicação da Sistematização da Assistência de Enfermagem (SAE), voltado para pessoas com agravos endócrinos e metabólicos no contexto hospitalar. Resultados e discussão: Foi aplicado a teoria da adaptação nas seis fases da Teoria de Calista Roy e foi elaborado diagnósticos de enfermagem para os quatro modos de adaptação: fisiológico, interdependência, autoconceito e função de papel. Considerações finais: Ao aplicar a SAE no indivíduo com agravos endócrinos e metabólicos a enfermeira deve realizá-lo em todas as suas etapas, e utilizar os protocolos para oferecer um cuidado holístico e integral, visando a promoção da saúde, prevenção de risco potencial e adaptação diante das necessidades em saúde.(AU)

The aim of this study is to describe the systematization of nursing care for people with endocrine and metabolic disorders, based on Calista Roy's theory. Methodology: This is an experience report on the application of the Systematization of Nursing Care (SNC) to people with endocrine and metabolic disorders in a hospital setting. Results and discussion: The theory of adaptation was applied in the six phases of Calista Roy's theory and nursing diagnoses were drawn up for the four modes of adaptation: physiological, interdependence, self-concept and role function. Final considerations: When applying the SNC to individuals with endocrine and metabolic disorders, the nurse must carry it out in all its stages, and use the protocols to offer holistic and comprehensive care, aimed at promoting health, preventing potential risks and adapting to health needs.(AU)

El objetivo de este estudio es describir la sistematización de los cuidados de enfermería a personas con trastornos endocrinos y metabólicos, basándose en la teoría de Calista Roy. Metodología: Se trata de un informe de experiencia sobre la aplicación de la Sistematización de los Cuidados de Enfermería (SNC) a personas con trastornos endocrinos y metabólicos en un entorno hospitalario. Resultados y discusión: Se aplicó la teoría de la adaptación en las seis fases de la teoría de Calista Roy y se elaboraron diagnósticos de enfermería para los cuatro modos de adaptación: fisiológica, interdependencia, autoconcepto y función de rol. Consideraciones finales: Al aplicar el SNC a individuos con trastornos endocrinos y metabólicos, la enfermera debe llevarlo a cabo en todas sus fases, y utilizar los protocolos para ofrecer cuidados holísticos e integrales, dirigidos a promover la salud, prevenir riesgos potenciales y adaptarse a las necesidades de salud.(AU)

Recent insights into the role of hormones during development and their functional regulation.

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.

Endocrine disruption in crustaceans: New findings and perspectives.

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.

The effects of environmental changes on the endocrine regulation of feeding in fishes.

Fishes are exposed to natural and anthropogenic changes in their environment, which can have major effects on their behaviour and their physiology, including feeding behaviour, food intake and digestive processes. These alterations are owing to the direct action of environmental physico-chemical parameters (i.e. temperature, pH, turbidity) on feeding physiology but can also be a consequence of variations in food availability. Food intake is ultimately regulated by feeding centres of the brain, which receive and process information from endocrine signals from both brain and peripheral tissues such as the gastrointestinal tract. These endocrine signals stimulate or inhibit food intake, and interact with each other to maintain energy homeostasis. Changes in environmental conditions might change feeding habits and rates, thus affecting levels of energy stores, and the expression of endocrine appetite regulators. This review provides an overview of how environmental changes and food availability could affect feeding and these endocrine networks in fishes. This article is part of the theme issue 'Endocrine responses to environmental variation: conceptual approaches and recent developments'.

Endocrine responses to environmental variation.

Hormones regulate most physiological functions and life history from embryonic development to reproduction. In addition to their roles in growth and development, hormones also mediate responses to the abiotic, social and nutritional environments. Hormone signalling is responsive to environmental changes to adjust phenotypes to prevailing conditions. Both hormone levels and receptor densities can change to provide a flexible system of regulation. Endocrine flexibility connects the environment to organismal function, and it is central to understanding environmental impacts and their effect on individuals and populations. Hormones may also act as a 'sensor' to link environmental signals to epigenetic processes and thereby effect phenotypic plasticity within and across generations. Many environmental parameters are now changing in unprecedented ways as a result of human activity. The knowledge base of organism-environmental interactions was established in environments that differ in many ways from current conditions as a result of ongoing human impacts. It is an urgent contemporary challenge to understand how evolved endocrine responses will modulate phenotypes in response to anthropogenic environmental impacts including climate change, light-at-night and chemical pollution. Endocrine responses play a central role in ecology, and their integration into conservation can lead to more effective outcomes. This article is part of the theme issue 'Endocrine responses to environmental variation: conceptual approaches and recent developments'.

Endocrine disruption in teleosts and amphibians is mediated by anthropogenic and natural environmental factors: implications for risk assessment.

Environmental variation in the Anthropocene involves several factors that interfere with endocrine systems of wildlife and humans, presenting a planetary boundary of still unknown dimensions. Here, we focus on chemical compounds and other impacts of anthropogenic and natural origins that are adversely affecting reproduction and development. The main sink of these endocrine disruptors (EDs) is surface waters, where they mostly endanger aquatic vertebrates, like teleost fish and amphibians. For regulatory purposes, EDs are categorized into EATS modalities (oestrogenic, androgenic, thyroidal, steroidogenesis), only addressing endocrine systems being assessable by validated tests. However, there is evidence that non-EATS modalities-and even natural sources, such as decomposition products of plants or parasitic infections-can affect vertebrate endocrine systems. Recently, the disturbance of natural circadian light rhythms by artificial light at night (ALAN) has been identified as another ED. Reviewing the knowledge about EDs affecting teleosts and amphibians leads to implications for risk assessment. The generally accepted WHO-definition for EDs, which focuses exclusively on 'exogenous substances' and neglects parasitic infections or ALAN, seems to require some adaptation. Natural EDs have been involved in coevolutionary processes for ages without resulting in a general loss of biodiversity. Therefore, to address the 'One Health'-principle, future research and regulatory efforts should focus on minimizing anthropogenic factors for endocrine disruption. This article is part of the theme issue 'Endocrine responses to environmental variation: conceptual approaches and recent developments'.

Multi-omics Investigations in Endocrine Systems and Their Clinical Implications.

Innovative techniques such as the "omics" can be a powerful tool for the understanding of intracellular pathways involved in homeostasis maintenance and identification of new potential therapeutic targets against endocrine-metabolic disorders. Over the last decades, proteomics has been extensively applied in the study of a wide variety of human diseases, including those involving the endocrine system. Among the most endocrine-related disorders investigated by proteomics in humans are diabetes mellitus and thyroid, pituitary, and reproductive system disorders. In diabetes, proteins implicated in insulin signaling, glucose metabolism, and ß-cell activity have been investigated. In thyroid diseases, protein expression alterations were described in thyroid malignancies and autoimmune thyroid illnesses. Additionally, proteomics has been used to investigate the variations in protein expression in adrenal cancers and conditions, including Cushing's syndrome and Addison's disease. Pituitary tumors and disorders including acromegaly and hypopituitarism have been studied using proteomics to examine changes in protein expression. Reproductive problems such as polycystic ovarian syndrome and endometriosis are two examples of conditions where alterations in protein expression have been studied using proteomics. Proteomics has, in general, shed light on the molecular underpinnings of many endocrine-related illnesses and revealed promising biomarkers for both their detection and treatment. The capacity of proteomics to thoroughly and objectively examine complex protein mixtures is one of its main benefits. Mass spectrometry (MS) is a widely used method that identifies and measures proteins based on their mass-to-charge ratio and their fragmentation pattern. MS can perform the separation of proteins according to their physicochemical characteristics, such as hydrophobicity, charge, and size, in combination with liquid chromatography. Other proteomics techniques include protein arrays, which enable the simultaneous identification of several proteins in a single assay, and two-dimensional gel electrophoresis (2D-DIGE), which divides proteins depending on their isoelectric point and molecular weight. This chapter aims to summarize the most relevant proteomics data from targeted tissues, as well as the daily rhythmic variation of relevant biomarkers in both physiological and pathophysiological conditions within the involved endocrine system, especially because the actual modern lifestyle constantly imposes a chronic unentrained condition, which virtually affects all the circadian clock systems within human's body, being also correlated with innumerous endocrine-metabolic diseases.

The role of microbial metabolites in endocrine tumorigenesis: From the mechanistic insights to potential therapeutic biomarkers.

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.

The Role of the Endocrine System in the Regulation of Acid-Base Balance by the Kidney and the Progression of Chronic Kidney Disease.

Systemic acid-base status is primarily determined by the interplay of net acid production (NEAP) arising from metabolism of ingested food stuffs, buffering of NEAP in tissues, generation of bicarbonate by the kidney, and capture of any bicarbonate filtered by the kidney. In chronic kidney disease (CKD), acid retention may occur when dietary acid production is not balanced by bicarbonate generation by the diseased kidney. Hormones including aldosterone, angiotensin II, endothelin, PTH, glucocorticoids, insulin, thyroid hormone, and growth hormone can affect acid-base balance in different ways. The levels of some hormones such as aldosterone, angiotensin II and endothelin are increased with acid accumulation and contribute to an adaptive increase in renal acid excretion and bicarbonate generation. However, the persistent elevated levels of these hormones can damage the kidney and accelerate progression of CKD. Measures to slow the progression of CKD have included administration of medications which inhibit the production or action of deleterious hormones. However, since metabolic acidosis accompanying CKD stimulates the secretion of several of these hormones, treatment of CKD should also include administration of base to correct the metabolic acidosis.

Evaluation of fish pituitary spheroids to study annual endocrine reproductive control.

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.

Endocrine Disruptors and Metabolic Changes: Impact on Puberty Control.

OBJECTIVE: This study aims to explore the significant impact of environmental chemicals on disease development, focusing on their role in developing metabolic and endocrine diseases. The objective is to understand how these chemicals contribute to the increasing prevalence of precocious puberty, considering various factors, including epigenetic changes, lifestyle, and emotional disturbances. METHODS: The study employs a comprehensive review of descriptive observational studies in both human and animal models to identify a degree of causality between exposure to environmental chemicals and disease development, specifically focusing on endocrine disruption. Due to ethical constraints, direct causation studies in human subjects are not feasible; therefore, the research relies on accumulated observational data. RESULTS: Puberty is a crucial life period with marked physiological and psychological changes. The age at which sexual characteristics develop is changing in many regions. The findings indicate a correlation between exposure to endocrine-disrupting chemicals and the early onset of puberty. These chemicals have been shown to interfere with normal hormonal processes, particularly during critical developmental stages such as adolescence. The research also highlights the interaction of these chemical exposures with other factors, including nutritional history, social and lifestyle changes, and emotional stress, which together contribute to the prevalence of precocious puberty. CONCLUSION: Environmental chemicals significantly contribute to the development of certain metabolic and endocrine diseases, particularly in the rising incidence of precocious puberty. Although the evidence is mainly observational, it adequately justifies regulatory actions to reduce exposure risks. Furthermore, these findings highlight the urgent need for more research on the epigenetic effects of these chemicals and their wider impact on human health, especially during vital developmental periods.