Chromogranin A: An Endocrine Factor of Pregnancy.

Pregnancy is a state of physiological and hormonal changes. One of the endocrine factors involved in these processes is chromogranin A, an acidic protein produced, among others, by the placenta. Although it has been previously linked to pregnancy, no existing articles have ever managed to clarify the role of this protein regarding this subject. Therefore, the aim of the present study is to gather knowledge of chromogranin A's function with reference to gestation and parturition, clarify elusive information, and, most importantly, to formulate hypotheses for the future studies to verify.

Future directions in urban endocrinology - The effects of endocrine plasticity on urban tolerance.

After twenty years of studies of endocrine traits in animals living in cities, the field of urban endocrinology has built a robust literature including numerous studies looking for signatures of the effects of urban living, usually in mean circulating hormone concentrations. The findings of this past research have primarily demonstrated the absence of any generalizable endocrine responses to city life. In this opinion paper, I suggest that a strong route forward would include investigations of the role of variation in endocrine plasticity in determining the degree to which organisms tolerate urban challenges (i.e., urban tolerance). Achieving this research aim will require creative experimental and comparative studies, consideration of alternative study systems, and teasing apart of sources of variation in plastic phenotypes (plasticity, sorting, and contemporary evolution). Insight into the role of endocrine plasticity in influencing urban tolerance could help us better understand and predict impacts of expanding urbanization on biodiversity across the globe.

Cytotoxicity, endocrine disrupting activity, and chemical analysis of 42 food contact silicone rubber products.

After migration in 95 % ethanol (food simulant) at 70 °C for 2 h (accelerated conditions), the cytotoxicity and endocrine-disruption activity of 42 food contact silicone products (FCSPs) obtained from the Chinese market were studied. Of 31 kitchenwares, 96 % showed mild or above cytotoxicity (relative growth rate < 80 %) using the HeLa neutral red uptake test; and 84 % showed estrogenic (64 %), anti-estrogenic (19 %), androgenic (42 %), and anti-androgenic (39 %) activities by the Dual-luciferase reporter gene assay. The mold sample induced late phase HeLa apoptosis as detected by Annexin V-FITC/PI double staining flow cytometry, in addition, the migration of mold sample has a higher risk of endocrine disruption at high temperature usage. Encouragingly, 11 bottle nipples had neither cytotoxic nor hormonal activity. Utilizing multiple mass spectrometry techniques, non-intentionally added substances (NIASs) in 31 kitchenwares were analyzed, and the migration levels of 26 organic compounds and 21 metals were quantified, furthermore, the safe risk of single migrant was evaluated through their special migration limit (SML) or threshold of toxicological concern (TTC). Using "nchoosek" statement and Spearman's correlation analysis in MATLAB, the migration of 38 compounds or combinations including metals, plasticizers, methylsiloxanes, and lubricants, had strong correlation with cytotoxicity or hormonal activity. The coexistence of various chemical substances in migrants leads to complex biological toxicity of FCSPs, so it is very important to detect the toxicity of the final products. The combination of bioassays and chemical analyses are valuable tools to facilitate the identification and analyses of FCSPs and migrants that have potential safety risks.

Burns: Classification, Pathophysiology, and Treatment: A Review.

Burns and their treatment are a significant medical problem. The loss of the physical barrier function of the skin opens the door to microbial invasion and can lead to infection. The repair process of the damage caused by the burn is impaired due to the enhanced loss of fluids and minerals through the burn wound, the onset of hypermetabolism with the concomitant disruption of nutrient supply, and derangements in the endocrine system. In addition, the initiated inflammatory and free radical processes drive the progression of oxidative stress, the inhibition of which largely depends on an adequate supply of antioxidants and minerals. Clinical experience and research provide more and more data to make the treatment of patients with thermal injury increasingly effective. The publication discusses disorders occurring in patients after thermal injury and the methods used at various stages of treatment.

Comprehensive identification of gene expression fingerprints and biomarkers of sexual endocrine disruption in zebrafish embryo.

Endocrine disruptors (EDs), capable of modulating the sex hormone system of an organism, can exert long-lasting negative effects on reproduction in both humans and the environment. For these reasons, the properties of EDs prevent a substance from being approved for marketing. However, regulatory testing to evaluate endocrine disruption is time-consuming, costly, and animal-intensive. Here, we combined sublethal zebrafish embryo assays with transcriptomics and proteomics for well-characterized endocrine disrupting reference compounds to identify predictive biomarkers for sexual endocrine disruption in this model. Using RNA and protein gene expression fingerprints from two different sublethal exposure concentrations, we identified specific signatures and impaired biological processes induced by ethinylestradiol, tamoxifen, methyltestosterone and flutamide 96 h post fertilization (hpf). Our study promotes vtg1 as well as cyp19a1b, fam20cl, lhb, lpin1, nr1d1, fbp1b, and agxtb as promising biomarker candidates for identifying and differentiating estrogen and androgen receptor agonism and antagonism. Evaluation of these biomarkers for pre-regulatory zebrafish embryo-based bioassays will help identify endocrine disrupting hazards of compounds at the molecular level. Such approaches additionally provide weight-of-evidence for the identification of putative EDs and may contribute significantly to a reduction in animal testing in higher tier studies.

A comparative study on endocrine disrupting effects of leachates from virgin and aged plastics under simulated media in marine medaka larvae (Oryzias melastigma).

Marine plastic pollution has garnered substantial attention, but the potential endocrine disrupting effects of plastic leachates in marine organisms remain unclear. In this study, the larvae of marine medaka (Oryzias melastigma) were exposed to the leachates from virgin and aged plastics soaked in simulated seawater and fish digest for 3 days. The concentrations of vitellogenin (VTG), estradiol (E2), and 11-ketotestosterone (11-KT), as well as the transcripts of endocrine-related genes were measured in the larvae. The results revealed that endogenous E2 was more sensitive to plastic leachates than VTG and 11-KT, which was significantly affected by 26.7 % of all plastic leachates. Among all genes, estrogen receptor α was impacted mostly, being up-regulated by 53.3 % of leachates from aged plastics. The comparative results demonstrated that the leachates from plastics with different statuses caused a greater difference than those from plastics in different simulated media, and the leachates from aged plastics resulted in higher endocrine disrupting effects than those from virgin plastics. In addition, seven leached additives (plasticizers and flame retardants) could explain 25.6 % of the hormonal effects using redundancy analysis, indicating that other additives in the plastic leachates can also play important roles in regulating the endocrine system of O. melastigma larvae.

Prediction of the Endocrine disruption profile of fluorinated biphenyls and analogues: An in silico study.

Fluorinated biphenyls and their analogues (FBAs) are considered new persistent organic pollutants, but their endocrine-disrupting effects are still unknown. To fill this gap, the binding probability of 44 FBAs to different nuclear hormone receptors (NHRs) was predicted using Endocrine Disruptome. And molecular similarity and network toxicology analysis were used to strengthen the docking screening. The docking results showed that FBAs could have high binding potential for various NHRs, such as estrogen receptors ß antagonism (ERß an), liver X receptors α (LXRα), estrogen receptors α (ERα), and liver X receptors ß (LXRß). The similarity analysis found that the degree of overlap of the NHR repertoire was related to the Tanimoto coefficient of FBAs. Network toxicology verified a part of docking screening results and identified endocrine-disrupting pathways worthy of attention. This study found out potential endocrine-disrupting FBAs and their vulnerable, and developed a workflow that would leverage in silico approaches including molecular docking, similarity, and network toxicology for risk prioritization of potential endocrine-disrupting compounds.

Recommendations for the diagnosis and treatment of patients with early breast cancer: update 2023.

PURPOSE OF REVIEW: In recent years, the therapy of breast carcinoma has evolved at a rapid pace. Therapies from metastasis are pushing into the (neo)adjuvant treatment of breast carcinoma at ever shorter intervals. RECENT FINDINGS: Biomarker-based therapeutic approaches became more and more en vogue to guide (neo)adjuvant endocrine therapy and chemotherapy. SUMMARY: This article reviews recent data developments in early breast cancer (EBC) and current recommendations in diagnosis and therapy.

Evolving roles of activins and inhibins in ovarian cancer pathophysiology.

Activins and inhibins are unique members of the transforming growth factor-ß (TGFß) family of growth factors, with the ability to exert autocrine, endocrine, and paracrine effects in a wide range of complex physiologic and pathologic processes. Although first isolated within the pituitary, emerging evidence suggests broader influence beyond reproductive development and function. Known roles of activin and inhibin in angiogenesis and immunity along with correlations between gene expression and cancer prognosis suggest potential roles in tumorigenesis. Here, we present a review of the current understanding of the biological role of activins and inhibins as it relates to ovarian cancers, summarizing the underlying signaling mechanisms and physiologic influence, followed by detailing their roles in cancer progression, diagnosis, and treatment.

Toxicological signature for thyroid endocrine disruption of dichlorooctylisothiazolinone in zebrafish larvae.

Dichlorooctylisothiazolinone (DCOIT), which is one of the isothiazolinone preservatives, is applied to water-based adhesives in food packaging. This study investigated the effects of DCOIT on the embryonic growth and thyroid endocrine system using zebrafish. Organism-level (hatchability, survival, and growth), hormone-level (triiodothyronine (T3) and thyroxine (T4)), gene-level (genes associated with the hypothalamus-pituitary-thyroid axis), and microRNA-level (microRNAs related to thyroid endocrine disruption) endpoints were measured. Significant rise in embryonic coagulation and delayed hatching (≥0.3 µg/L), and decreased larval length (30 µg/L) were observed in fish exposed to DCOIT. Lower contents of T3 and T4 were observed after exposure to DCOIT, which was accompanied by the upregulation of genes associated with the thyrotropin releasing hormone and thyroid stimulating hormone and the downregulation of genes associated with the thyroid hormone receptors and deiodination. Strong influence of DCOIT on dre-miR-193b and -499 may be a critical mechanism to inhibit transcription of trαa and trß, which in turn may affect thyroid hormones and development of the organism. Our findings suggest that hypothyroidism induced by the exposure to DCOIT is potentially associated with genetic and microRNA-level changes, which eventually affects development.

Thyroid endocrine disruption and neurotoxicity of gestodene in adult female mosquitofish (Gambusia affinis).

The frequent detection of progestins in various aquatic environments and their potential endocrine disruptive effects in fish have attracted increasing attention worldwide. However, data on their effects on thyroid function and neurotoxicity in fish are limited, and the underlying mechanisms remain unclear. Here, the effects of gestodene (GES, a common progestin) on the thyroid endocrine and nervous systems of mosquitofish (Gambusia affinis) were studied. Adult female fish were exposed to GES at environmentally relevant concentrations (4.4-378.7 ng/L) for 60 days. The results showed that exposure to 378.7 ng/L GES caused a significant decrease in fish growth compared with the control and a marked reduction in the total distance traveled (50.6%) and swimming velocity (40.1-61.9%). The triiodothyronine (T3) levels were significantly increased by GES in a dose-dependent manner, whereas those of tetraiodothyronine (T4) were significantly decreased only at the G500 concentration. The acetylcholinesterase (AChE) activity was decreased significantly in the 4.42 ng/L GES treatments, but increased significantly at 378.67 ng/L. In the brain, a strong increase in the transcriptional levels of bdnf, trh, and dio2 was observed in fish after the 378.7 ng/L treatment. In addition, chronic exposure to GES caused colloid depletion with a concentration-dependent manner in the thyroid, and angiectasis, congestion, and vacuolar necrosis in the brain. These findings provide a better understanding of the effects of GES and associated underlying mechanisms in G. affinis.

Histopathological and transcriptomic analyses reveal the reproductive endocrine-disrupting effects of decabromodiphenyl ethane (DBDPE) in mussel Mytilus galloprovincialis.

The novel brominated flame retardant DBDPE has become a widespread environmental contaminant and could affect reproductive endocrine system in vertebrates. However, information about reproductive endocrine-disrupting effects of DBDPE on invertebrates is totally unknown. In this study, mussels Mytilus galloprovincialis were exposed to 1, 10, 50, 200 and 500 µg/L DBDPE for 30 days. Histopathological and transcriptomic analyses were performed to assess the reproductive endocrine-disrupting effects of DBDPE in mussels and the potential mechanisms. DBDPE promoted the gametogenesis in mussels of both sexes according to histological observation, gender-specific gene expression (VERL and VCL) and histological morphometric parameter analysis. Transcriptomic analysis demonstrated that DBDPE suppressed the genes related to cholesterol homeostasis and transport in both sexes via different LRPs- and ABCs-mediated pathways. DBDPE also disturbed nongenomic signaling pathway including signaling cascades (GPR157-IP3-Ca2+) in males and secondary messengers (cGMP) in females, and subsequently altered the expression levels of reproductive genes (VMO1, ZAN, Banf1 and Hook1). Additionally, dysregulation of energy metabolism in male mussels induced by DBDPE might interfere with the reproductive endocrine system. Overall, this is the first report that DBDPE evoked reproductive endocrine-disruptions in marine mussels. These findings will provide important references for ecological risk assessment of DBDPE pollution in marine environment.

Advances in Endocrine Surgery.

Recent changes in the landscape of endocrine surgery include a shift from total thyroidectomy for almost all patients with papillary thyroid cancer to the incorporation of thyroid lobectomy for well-selected patients with low-risk disease; minimally invasive parathyroidectomy with, and potentially without, intraoperative parathyroid hormone monitoring for patients with well-localized primary hyperparathyroidism; improvement in the management of parathyroid cancer with the incorporation of immune checkpoint blockade and/or targeted therapies; and the incorporation of minimally invasive techniques in the management of patients with benign tumors and selected secondary malignancies of the adrenal gland.

The immune-stress/endocrine-redox-metabolic nature of psychosis' etiopathology; focus on the intersystemic pathways interactions.

The evidence supporting the involvement of a number of systems in the neurobiological etiopathology of psychosis has recently grown exponentially. Indeed, the focus of research has changed from measuring solely neurotransmitters to estimating parameters from fields like immunity, stress/endocrine, redox, and metabolism. Yet, little is known regarding the exact role of each one of these fields on the formation of not only the brain neuropathological substrate in psychosis but also the associated general systemic pathology, in terms of causality directions. Research has shown deviations in the levels and/or function of basic effector molecules of the aforementioned fields namely cytokines, pro-/anti- oxidants, glucocorticoids, catecholamines, glucose, and lipids metabolites as well as kynurenines, in psychosis. Yet the evidence regarding their impact on neurotransmitters is minimal and the findings concerning these systems' interactions in the psychotic context are even more dispersed. The present review aims to draw holistically the frame of the hitherto known "players" in the field of psychosis' cellular pathobiology, with a particular focus on their in-between interactions.

Acute exposure to microcystins affects hypothalamic-pituitary axes of male rats.

Microcystins (MCs) produced by some cyanobacteria can cause toxicity in animals and humans. In recent years, growing evidence suggests that MCs can act as endocrine disruptors. This research systematically investigated effects of microcystin-LR (MC-LR) on endocrine organs, biosynthesis of hormones and positive/negative feedback of the endocrine system in rats. Male, Sprague-Dawley rats were acutely administrated MC-LR by a single intraperitoneal injection at doses of 45, 67.5 or 90 µg MC-LR/kg body mass (bm), and then euthanized 24 h after exposure. In exposed rats, histological damage of hypothalamus, pituitary, adrenal, testis and thyroid were observed. Serum concentrations of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT), expressions of genes and proteins for biosynthesis of hormones were lesser, which indicated an overall suppression of the hypothalamus-pituitary-adrenal (HPA) axis. Along the hypothalamus-pituitary-gonadal (HPG) axis, lesser concentrations of gonadotropin-releasing hormone (GnRH) and testosterone (T), but greater concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol (E2) were observed. Except for greater transcription of cyp19a1 in testes, transcriptions of genes and proteins for T and E2 biosynthesis along the HPG axis were lesser. As for the hypothalamus-pituitary-thyroid (HPT) axis, after MCs treatment, greater concentrations of thyroid-stimulating hormone (TSH), but lesser concentrations of free tri-iodothyronine (fT3) were observed in serum. Concentrations of free tetra-iodothyronine (fT4) were greater in rats dosed with 45 µg MCs/kg, bm, but lesser in rats dosed with 67.5 or 90 µg MCs/kg, bm. Transcripts of genes for biosynthesis of hormones and receptors along the HPT axis and expressions of proteins for biosynthesis of tetra-iodothyronine (T4) and tri-iodothyronine (T3) in thyroid were significantly altered. Cross-talk among the HPA, HPG and HPT axes probably occurred. It was concluded that MCs caused an imbalance of positive and negative feedback of hormonal regulatory axes, blocked biosynthesis of key hormones and exhibited endocrine-disrupting effects.

Azole pesticide products and their hepatic metabolites cause endocrine disrupting potential by suppressing the homo-dimerization of human estrogen receptor alpha.

We selected azole pesticides products that are managed by setting maximum residue limits (MRLs) in the Republic of Korea and describe the estrogen receptor (ER) α-related negative effect to endocrine system using in vitro Organization for Economic Cooperation and Development performance-based test guideline. No azoles were found to be an ERα agonist. Conversely, three azoles (bitertanol, cafenstrole, and tebufenpyrad) were determined to be ERα antagonists. In addition, the ERα antagonistic activities of bitertanol, cafenstrole, and tebufenpyrad were not significantly perturbed in the existence of phase I (hydroxylation, dealkylation, oxidation or reduction) and phase II (conjugation). Regarding the mechanism underlying their ERα-mediated endocrine disrupting potentials, ERα proteins cannot be translocated to the nucleus by suppressing the dimerization of ERα in the cytoplasm by bitertanol, cafenstrole, and tebufenpyrad. These data indicated that azole pesticide products show the capability to interfere the ERα-related human endocrine system. Furthermore, we identified the mechanism of ERα-mediated endocrine disrupting by azole insecticide products through this study.

Changes in DNA Methylation of Clock Genes in Obese Adolescents after a Short-Term Body Weight Reduction Program: A Possible Metabolic and Endocrine Chrono-Resynchronization.

Circadian rhythms are generated by a series of genes, collectively named clock genes, which act as a self-sustained internal 24 h timing system in the body. Many physiological processes, including metabolism and the endocrine system, are regulated by clock genes in coordination with environmental cues. Loss of the circadian rhythms has been reported to contribute to widespread obesity, particularly in the pediatric population, which is increasingly exposed to chronodisruptors in industrialized society. The aim of the present study was to evaluate the DNA methylation status of seven clock genes, namely clock, arntl, per1-3 and cry1-2, in a cohort of chronobiologically characterized obese adolescents (n: 45: F/M: 28/17; age ± SD: 15.8 ± 1.4 yrs; BMI SDS: 2.94 [2.76; 3.12]) hospitalized for a 3-week multidisciplinary body weight reduction program (BWRP), as well as a series of cardiometabolic outcomes and markers of hypothalamo-pituitary-adrenal (HPA) function. At the end of the intervention, an improvement in body composition was observed (decreases in BMI SDS and fat mass), as well as glucometabolic homeostasis (decreases in glucose, insulin, HOMA-IR and Hb1Ac), lipid profiling (decreases in total cholesterol, LDL-C, triglycerides and NEFA) and cardiovascular function (decreases in systolic and diastolic blood pressures and heart rate). Moreover, the BWRP reduced systemic inflammatory status (i.e., decrease in C-reactive protein) and HPA activity (i.e., decreases in plasma ACTH/cortisol and 24 h urinary-free cortisol excretion). Post-BWRP changes in the methylation levels of clock, cry2 and per2 genes occurred in the entire population, together with hypermethylation of clock and per3 genes in males and in subjects with metabolic syndrome. In contrast to the pre-BWRP data, at the end of the intervention, cardiometabolic parameters, such as fat mass, systolic and diastolic blood pressures, triglycerides and HDL-C, were associated with the methylation status of some clock genes. Finally, BWRP induced changes in clock genes that were associated with markers of HPA function. In conclusion, when administered to a chronodisrupted pediatric obese population, a short-term BWRP is capable of producing beneficial cardiometabolic effects, as well as an epigenetic remodeling of specific clock genes, suggesting the occurrence of a post-BWRP metabolic and endocrine chronoresynchronization, which might represent a "biomolecular" predictor of successful antiobesity intervention.