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1.
Environ Pollut ; 265(Pt B): 114362, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32806436

RESUMO

This study aimed to investigate the effect of mono-(2-ethylhexyl) phthalate (MEHP), one of the major phthalate metabolites that are widespread in aquatic environments, on reproductive dysfunction, particularly on endocrine activity in adult male and female zebrafish. For 21 days, the zebrafish were exposed to test concentrations of MEHP (0, 2, 10, and 50 µg/mL) that were determined based on the effective concentrations (ECx) for zebrafish embryos. Exposure to 50 µg/mL MEHP in female zebrafish significantly decreased the number of ovulated eggs as well as the hepatic VTG mRNA abundance when those of the control group. Meanwhile, in female zebrafish, the biosynthetic concentrations of 17ß-estradiol (E2) and the metabolic ratio of androgen to estrogen were remarkably increased in all MEHP exposed group compared with those in the control group, along with the elevated levels of cortisol. However, no significant difference was observed between these parameters in male zebrafishes. Therefore, exposure to MEHP causes reproductive dysfunction in female zebrafishes and this phenomenon can be attributed to the alteration in endocrine activities. Moreover, the reproductive dysfunction in MEHP-exposed female zebrafishes may be closely associated with stress responses, such as elevated cortisol levels. To further understand the effect of MEHP on the reproductive activities of fish, follow-up studies are required to determine the interactions between endocrine activities and stress responses. Overall, this study provides a response biomarker for assessing reproductive toxicity of endocrine disruptors that can serve as a methodological approach for an alternative to chronic toxicity testing.


Assuntos
Ácidos Ftálicos , Peixe-Zebra , Animais , Conexinas , Dietilexilftalato/análogos & derivados , Sistema Endócrino , Feminino , Masculino , Proteínas de Peixe-Zebra
2.
Adv Exp Med Biol ; 1265: 97-109, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32761572

RESUMO

Dietary amino acids play an important role in maintaining health. Branched chain amino acids can adversely increase blood pressure whereas arginine and citrulline can reduce it. D-amino acids play important roles in several cell types including testis, the nervous system and adrenal glands. Several amino acids also can have dramatic effects on diabetes; branched chain amino acids, phenylalanine and tyrosine have been implicated while others, namely arginine and citrulline can improve outcomes. Leucine has been shown to play important roles in muscle primarily through the mTOR pathway though this effect does not translate across every population. Glutamine, arginine and D-aspartate also exert their muscle effects through mTOR. Relationships between amino acids and endocrine function include that of glucocorticoids, thyroid function, glucagon-like peptide 1 (GLP-1), ghrelin, insulin-like growth factor-1 (IGF-1) and leptin. Leucine, for example, can alleviate the effect of dexamethasone on muscle protein accretion. Interestingly, amino acid transporters play an important role in thyroid function. Several amino acids have been shown to increase GLP-1 levels in non-diabetics when administered orally. Similarly, several amino acids increase ghrelin levels in different species while cysteine can decrease it in mice. There is evidence to suggest that the arginine/NO pathway may be involved in modulating some of the effects of ghrelin on cells. In regard to IGF-1, branched chain amino acids can increase levels in adults while tryptophan and phenylalanine have been shown to increase levels in infants. Finally, leptin levels can be elevated by branched chain amino acids while restricting leucine in high fat diets can increase leptin sensitivity.


Assuntos
Aminoácidos/metabolismo , Sistema Endócrino/metabolismo , Animais , Grelina , Humanos
3.
Ugeskr Laeger ; 182(29)2020 07 13.
Artigo em Dinamarquês | MEDLINE | ID: mdl-32734864

RESUMO

Coronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome corona virus 2. High age, hypertension, diabetes, and obesity are risk factors for severe COVID-19 with increased mortality. In this review, we discuss potential mechanisms by which diabetes and obesity modulate the host viral interactions and host-immune response. Glucose levels should be monitored rigorously, and patient-tailored aggressive treatment of hyperglycaemia is recommended, often with the use of insulin. Persons with diabetes and obesity are susceptible to severe outcomes from COVID-19.


Assuntos
Infecções por Coronavirus/complicações , Diabetes Mellitus/virologia , Interações entre Hospedeiro e Microrganismos , Obesidade/complicações , Pneumonia Viral/complicações , Betacoronavirus , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/metabolismo , Diabetes Mellitus/metabolismo , Sistema Endócrino , Humanos , Hiperglicemia/tratamento farmacológico , Insulina/uso terapêutico , Obesidade/metabolismo , Obesidade/virologia , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/metabolismo , Fatores de Risco
4.
Proc Biol Sci ; 287(1930): 20200722, 2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32635860

RESUMO

Many animals differentially express behaviours across the annual cycle as life stages are coordinated with seasonal environmental conditions. Understanding of the mechanistic basis of such seasonal changes in behaviour has traditionally focused on the role of changes in circulating hormone levels. However, it is increasingly apparent that other endocrine regulation mechanisms such as changes in local hormone synthesis and receptor abundance also play a role. Here I review what is known about seasonal changes in steroid hormone receptor abundance in relation to seasonal behaviour in vertebrates. I find that there is widespread, though not ubiquitous, seasonal variation in the expression of steroid hormone receptors in the brain, with such variation being best documented in association with courtship, mating and aggression. The most common pattern of seasonal variation is for there to be upregulation of sex steroid receptors with the expression of courtship and mating behaviours, when circulating hormone levels are also high. Less well-documented are cases in which seasonal increases in receptor expression could compensate for low circulating hormone levels or seasonal downregulation that could serve a protective function. I conclude by identifying important directions for future research.


Assuntos
Comportamento Animal/fisiologia , Hormônios Esteroides Gonadais/metabolismo , Animais , Sistema Endócrino , Feminino , Masculino , Reprodução , Estações do Ano , Vertebrados
5.
Sci Total Environ ; 735: 139496, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32480152

RESUMO

Pyriproxyfen (PPF), a broad-spectrum insecticide known to cause reproductive and endocrine disruption in invertebrates, while the data is scarce in aquatic vertebrates. The goal of this study is to investigate the impact of PPF on reproductive endocrine system of male and female zebrafish along hypothalamus-pituitary-gonadal (HPG) axis. In brain, PPF caused significant alteration in the transcripts of erα, lhß, and cyp19b genes in male and fshß, lhß, and cyp19b genes in female zebrafish. The downstream genes of steroidogenic pathway like, star, 3ßhsd, 17ßhsd, and cyp19a expression were significantly altered in gonad of both sexes. Subsequent changes in circulatory steroid hormone levels lead to imbalance in hormone homeostasis as revealed from estradiol/testosterone (E2/T) ratio. Further, the vitellogenin transcript level was enhanced in hepatic tissues and their blood plasma content was increased in male (16.21%) and declined in female (21.69%). PPF also induced histopathological changes in gonads such as, reduction of mature spermatocytes in male and vitellogenic oocytes in female zebrafish. The altered E2/T ratio and gonadal histopathology were supported by the altered transcript levels of HPG axis genes. Overall, these findings provide new insights of PPF in zebrafish reproductive system and highlights for further investigations on its potential risks in aquatic environment.


Assuntos
Disruptores Endócrinos , Poluentes Químicos da Água/farmacologia , Animais , Sistema Endócrino/efeitos dos fármacos , Feminino , Gônadas/efeitos dos fármacos , Homeostase , Hipotálamo , Masculino , Piridinas , Reprodução , Vitelogeninas , Peixe-Zebra
6.
Ecotoxicol Environ Saf ; 201: 110820, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32531574

RESUMO

Growth hormone (GH)/insulin-like growth factor (IGF) axis plays a critical role in fetal development. However, the effect of arsenite exposure on the GH/IGF axis and its toxic mechanism are still unclear. Zebrafish embryos were exposed to a range of NaAsO2 concentrations (0.0-10.0 mM) between 4 and 120 h post-fertilization (hpf). Development indexes of survival, malformation, hatching rate, heart rate, body length and locomotor behavior were measured. Hormone levels, GH/IGF axis-related genes, and nerve-related genes were also tested. The results showed that survival rate, hatching rate, heart rate, body length and locomotor behavior all decreased, while deformity increased. At 120 hpf, the survival rate of zebrafish in 1.5 mM NaAsO2 group was about 70%, the deformity rate exceeded 20%, and the body length shortened to 3.35 mm, the movement distance of zebrafish decreased approximately 63.6% under light condition and about 52.4% under dark condition. The level of GH increased and those of IGF did not change significantly, while the expression of GH/IGF axis related genes (ghra, ghrb, igf2r, igfbp3, igfbp2a, igfbp5b) and nerve related genes (dlx2, shha, ngn1, elavl3, gfap) decreased. In 1.5 mM NaAsO2 group, the decrease of igfbp3 and igfbp5b was almost obvious, about 78.2% and 72.2%. The expression of nerve genes in 1.5 mM NaAsO2 group all have declined by more than 50%. These findings suggested that arsenite exerted disruptive effects on the endocrine system by interfering with the GH/IGF axis, leading to zebrafish embryonic developmental toxicity.


Assuntos
Arsenitos/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Hormônio do Crescimento/metabolismo , Somatomedinas/metabolismo , Peixe-Zebra , Animais , Embrião não Mamífero/metabolismo , Desenvolvimento Embrionário/genética , Sistema Endócrino/efeitos dos fármacos , Sistema Endócrino/embriologia , Sistema Endócrino/metabolismo , Hormônio do Crescimento/genética , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética , Transdução de Sinais , Somatomedinas/genética , Peixe-Zebra/genética , Peixe-Zebra/metabolismo
7.
Chem Biol Interact ; 326: 109099, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32370863

RESUMO

Theoretically, both synthetic endocrine disrupting chemicals (S-EDCs) and natural (exogenous and endogenous) endocrine disrupting chemicals (N-EDCs) can interact with endocrine receptors and disturb hormonal balance. However, compared to endogenous hormones, S-EDCs are only weak partial agonists with receptor affinities several orders of magnitude lower. Thus, to elicit observable effects, S-EDCs require considerably higher concentrations to attain sufficient receptor occupancy or to displace natural hormones and other endogenous ligands. Significant exposures to exogenous N-EDCs may result from ingestion of foods such as soy-based diets, green tea and sweet mustard. While their potencies are lower as compared to natural endogenous hormones, they usually are considerably more potent than S-EDCs. Effects of exogenous N-EDCs on the endocrine system were observed at high dietary intakes. A causal relation between their mechanism of action and these effects is established and biologically plausible. In contrast, the assumption that the much lower human exposures to S-EDCs may induce observable endocrine effects is not plausible. Hence, it is not surprising that epidemiological studies searching for an association between S-EDC exposure and health effects have failed. Regarding testing for potential endocrine effects, a scientifically justified screen should use in vitro tests to compare potencies of S-EDCs with those of reference N-EDCs. When the potency of the S-EDC is similar or smaller than that of the N-EDC, further testing in laboratory animals and regulatory consequences are not warranted.


Assuntos
Disruptores Endócrinos/efeitos adversos , Sistema Endócrino/efeitos dos fármacos , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/efeitos adversos , Animais , Humanos
8.
PLoS Genet ; 16(5): e1008361, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32463812

RESUMO

Osteocalcin (OCN), the most abundant noncollagenous protein in the bone matrix, is reported to be a bone-derived endocrine hormone with wide-ranging effects on many aspects of physiology, including glucose metabolism and male fertility. Many of these observations were made using an OCN-deficient mouse allele (Osc-) in which the 2 OCN-encoding genes in mice, Bglap and Bglap2, were deleted in ES cells by homologous recombination. Here we describe mice with a new Bglap and Bglap2 double-knockout (dko) allele (Bglap/2p.Pro25fs17Ter) that was generated by CRISPR/Cas9-mediated gene editing. Mice homozygous for this new allele do not express full-length Bglap or Bglap2 mRNA and have no immunodetectable OCN in their serum. FTIR imaging of cortical bone in these homozygous knockout animals finds alterations in the collagen maturity and carbonate to phosphate ratio in the cortical bone, compared with wild-type littermates. However, µCT and 3-point bending tests do not find differences from wild-type littermates with respect to bone mass and strength. In contrast to the previously reported OCN-deficient mice with the Osc-allele, serum glucose levels and male fertility in the OCN-deficient mice with the Bglap/2pPro25fs17Ter allele did not have significant differences from wild-type littermates. We cannot explain the absence of endocrine effects in mice with this new knockout allele. Possible explanations include the effects of each mutated allele on the transcription of neighboring genes, or differences in genetic background and environment. So that our findings can be confirmed and extended by other interested investigators, we are donating this new Bglap and Bglap2 double-knockout strain to the Jackson Laboratories for academic distribution.


Assuntos
Sistema Endócrino/fisiologia , Osteocalcina/genética , Animais , Densidade Óssea/genética , Osso e Ossos/metabolismo , Sistema Endócrino/metabolismo , Feminino , Fertilidade/genética , Resistência à Insulina/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Osteocalcina/deficiência
9.
Nat Commun ; 11(1): 2132, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32358539

RESUMO

Brown adipose tissue (BAT) is known to secrete regulatory factors in response to thermogenic stimuli. Components of the BAT secretome may exert local effects that contribute to BAT recruitment and activation. Here, we found that a thermogenic stimulus leads to enhanced secretion of kininogen (Kng) by BAT, owing to induction of kininogen 2 (Kng2) gene expression. Noradrenergic, cAMP-mediated signals induce KNG2 expression and release in brown adipocytes. Conversely, the expression of kinin receptors, that are activated by the Kng products bradykinin and [Des-Arg9]-bradykinin, are repressed by thermogenic activation of BAT in vivo and of brown adipocytes in vitro. Loss-of-function models for Kng (the circulating-Kng-deficient BN/Ka rat) and bradykinin (pharmacological inhibition of kinin receptors, kinin receptor-null mice) signaling were coincident in showing abnormal overactivation of BAT. Studies in vitro indicated that Kng and bradykinin exert repressive effects on brown adipocyte thermogenic activity by interfering the PKA/p38 MAPK pathway of control of Ucp1 gene transcription, whereas impaired kinin receptor expression enhances it. Our findings identify the kallikrein-kinin system as a relevant component of BAT thermogenic regulation that provides auto-regulatory inhibitory signaling to BAT.


Assuntos
Tecido Adiposo Marrom/metabolismo , Calicreínas/metabolismo , Cininas/metabolismo , Animais , Bradicinina/genética , Bradicinina/metabolismo , Sistema Endócrino/metabolismo , Imunofluorescência , Calicreínas/genética , Cininogênios/genética , Cininogênios/metabolismo , Cininas/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/genética , Transdução de Sinais/fisiologia
11.
Zhongguo Zhong Yao Za Zhi ; 45(5): 997-1003, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32237438

RESUMO

To investigate the characteristics of the cold and heat properties of each resolution component of Açaí and the material basis of cooling by observing the effect of resolution components, such as Açaí oil, alcohol extract and water extract, on the neurotransmitter, endocrine hormone and immune factor level in mice with deficiency-heat and deficiency-cold syndrome. KM male mice were randomly divided into 12 groups, namely blank group, deficiency-heat model group, deficiency-heat+Açaí group, deficiency-heat+Açaí oil group, deficiency-heat+Açaí alcohol extract group, deficiency-heat+Açaí water extract group, deficiency-cold model group, deficiency-cold+Cinnamomi Cortex group, deficiency-cold+Açaí group, deficiency-cold+Açaí oil group, deficiency-cold+Açaí alcohol extract group, and deficiency-cold+Açaí water extract group. The mice in deficiency-heat group were given with thyroid tablet solution(160 mg·kg~(-1)), and the mice in deficiency-cold group were given with hydrocortisone solution(25 mg·kg~(-1)) by intragastric administration every afternoon for 14 days. The mice in each administration group received corresponding drug. The neurotransmitter, endocrine hormone and immune factor levels in the mice were measured after the experiment. The Açaí alcohol extract, consistent with the Açaí powder, showed a regulatory effect on the deficiency-heat model mice; Açaí oil and its water extract were consistent with Cinna-momi Cortex, showing a regulatory effect on the deficiency-cold model mice. In this study, on the basis of proving that Açaí was was cool in property, it also revealed that alcohol extract of Açaí was cool while oil and water extract were warm in property based on the effect of Açaí on neuro-endocrine-immune network. The results suggested that the medicine property of Açaí was the result of the comprehensive action of the resolution components with different properties, and the alcohol extract of Açaí was proved as the material basis of Açaí cold medicine by using the methods of homogeneous comparison and heterogeneous disproval.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Sistema Endócrino/efeitos dos fármacos , Euterpe/química , Sistema Imunitário/efeitos dos fármacos , Sistema Nervoso/efeitos dos fármacos , Animais , Hormônios/metabolismo , Fatores Imunológicos/metabolismo , Masculino , Camundongos , Neurotransmissores/metabolismo , Extratos Vegetais/farmacologia
12.
Zhongguo Zhong Yao Za Zhi ; 45(5): 1004-1010, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32237439

RESUMO

The aim of this paper was to study the effect of Lepidium meyenii(Maca) on cyclic nucleotides, neurotransmitter levels and hypothalamic-pituitary-adrenal axis and immunization of deficiency-cold and deficiency-heat syndrome rats, in order to explore the cold and hot medicinal properties of Maca. SD rats were divided into blank group, deficiency-cold syndrome group, Cinnamomi Cortex of deficiency-cold syndrome(30 g·kg~(-1)) group, high and low-dose Maca groups(2.4, 1.2 g·kg~(-1)), deficiency-heat syndrome group, Phellodendri Chinensis Cortex(PCC) of deficiency-heat syndrome(5 g·kg~(-1)), and high and low-dose Maca groups(2.4, 1.2 g·kg~(-1)). The rats were treated with intramuscular injection of hydrocortisone(20 mg·kg~(-1)) or dexamethasone sodium phosphate(0.35 mg·kg~(-1)) for 21 days to set up the deficiency-cold and deficiency-heat model. The levels of cAMP, cGMP, NE, DA, 5-HT, CRH, ACTH, CORT and IgM, IgG, C3, C4 were detected by radio immunoassay. Both the high-dose Maca group and the low-dose Maca group can significantly improve the overall state and body weight of rats with deficiency-cold syndrome(P<0.01, P<0.05), significantly increasing cAMP, cAMP/cGMP, NE, DA, ACTH(P<0.01, P<0.001), and significantly decreasing 5-HT(P<0.01, P<0.001). However, high-dose and low-dose Maca groups could not improve the deficiency-heat syndrome, and the levels of cAMP, cGMP, cAMP/cGMP, NE, DA, 5-HT and ACTH were not statistically significant. Maca had a significant regulatory effect on CORT, IgM, IgG and C3 content of rats with deficiency-cold and deficiency-heat syndrome(P<0.01, P<0.05, P<0.001). Maca showed the same effect with Cinnamomi Cortex in adjusting the levels of deficiency-cold rats, but in opposition to Phellodendri Chinese Cortex. This paper confirmed that Maca was slightly warm based on its effect on cyclic nucleotide levels and neuro-endocrine-immune networks by the pharmacological experimental method.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Sistema Endócrino/efeitos dos fármacos , Sistema Imunitário/efeitos dos fármacos , Lepidium/química , Sistema Nervoso/efeitos dos fármacos , Animais , Sistema Hipotálamo-Hipofisário , Medicina Tradicional Chinesa , Neurotransmissores , Nucleotídeos Cíclicos , Sistema Hipófise-Suprarrenal , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley , Temperatura
13.
Anaesthesia ; 75(6): 756-766, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32232991

RESUMO

Estimates of the rate and risk-factors for difficult airway rarely include a denominator for the number of anaesthetics. Approaches such as self-reporting and crowd-sourcing of airway incidents may help identify specific lessons from clinical episodes, but the lack of denominator data, biased reporting and under-reporting does not allow a comprehensive population-based assessment. We used an established state-wide dataset to determine the incidence of failed and difficult intubations between 2015 and 2017 in the state of Victoria in Australia, along with associated patient and surgical risk-factors. A total of 861,533 general anaesthesia episodes were analysed. Of these, 4092 patients with difficult or failed intubation were identified; incidence rates of 0.52% (2015-2016) and 0.43% (2016-2017), respectively. Difficult/failed intubations were most common in patients aged 45-75 and decreased for older age groups, with risk being lower for patients aged >85 than patients aged 35-44. The risk for failed/difficult intubation increased significantly for: patients undergoing emergency surgery (OR 1.80); obese patients (OR 2.48); increased ASA physical status; and increased Charlson Comorbidity Index. Across all age groups, procedures on the nervous system (OR 1.92) and endocrine system (OR 2.03) had the highest risk of failed/difficult intubation. The relative reduced risk for failed/difficult intubations in the elderly population is a novel finding that contrasts with previous research and may suggest a 'compression of morbidity' effect as a moderator. Administrative databases have the potential to improve understanding of peri-operative risk of rare events at a population level.


Assuntos
Tratamento de Emergência/estatística & dados numéricos , Nível de Saúde , Intubação Intratraqueal/métodos , Intubação Intratraqueal/estatística & dados numéricos , Obesidade/complicações , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anestesia Geral/estatística & dados numéricos , Criança , Pré-Escolar , Bases de Dados Factuais , Sistema Endócrino/cirurgia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/estatística & dados numéricos , Fatores de Risco , Vitória , Adulto Jovem
15.
Chemosphere ; 249: 126536, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32217413

RESUMO

This study investigated the influences of titanium dioxide nanoparticles (n-TiO2) on the thyroid endocrine disruption and neurobehavioral defects induced by pentachlorophenol (PCP) in zebrafish (Danio rerio). Embryos (2 h post-fertilization) were exposed to PCP (0, 3, 10, and 30 µg/L) or in combination with n-TiO2 (0.1 mg/L) until 6 days post-fertilization. The results showed that n-TiO2 alone did not affect thyroid hormones levels or transcriptions of related genes. Exposure to PCP significantly decreased thyroid hormone thyroxine (T4) content, thyroid stimulating hormone (TSH) level and transcription of thyroglobulin (tg), but significantly increased 3,5,3'-triiodothyronine (T3) level and upregulation of deiodinase 2 (dio2). In comparison, the co-exposure with n-TiO2 significantly reduced the content of T3 by depressing the potential targets, tg and dio2. For neurotoxicity, the single and co-exposure resulted in similar effects with significant downregulation of neurodevelopment-related genes (ELAV like RNA Binding Protein 3, elavl3; Growth associated protein-43, gap43; α-tubulin) and inhibited locomotor activity. The results indicated that the presence of n-TiO2 significantly enhanced the PCP-induced thyroid endocrine disruption but not the neurobehavioral defects in zebrafish larvae.


Assuntos
Disruptores Endócrinos/toxicidade , Pentaclorofenol/toxicidade , Peixe-Zebra/fisiologia , Animais , Sistema Endócrino/efeitos dos fármacos , Larva/efeitos dos fármacos , Nanopartículas/toxicidade , Pentaclorofenol/metabolismo , Glândula Tireoide/efeitos dos fármacos , Hormônios Tireóideos/metabolismo , Titânio/toxicidade , Tri-Iodotironina/metabolismo , Peixe-Zebra/metabolismo
16.
Nat Rev Endocrinol ; 16(5): 276-283, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32127696

RESUMO

Cancer is driven by incremental changes that accumulate, eventually leading to oncogenic transformation. Although genetic alterations dominate the way cancer biologists think about oncogenesis, growing evidence suggests that systemic factors (for example, insulin, oestrogen and inflammatory cytokines) and their intracellular pathways activate oncogenic signals and contribute to targetable phenotypes. Systemic factors can have a critical role in both tumour initiation and therapeutic responses as increasingly targeted and personalized therapeutic regimens are used to treat patients with cancer. The endocrine system controls cell growth and metabolism by providing extracellular cues that integrate systemic nutrient status with cellular activities such as proliferation and survival via the production of metabolites and hormones such as insulin. When insulin binds to its receptor, it initiates a sequence of phosphorylation events that lead to activation of the catalytic activity of phosphoinositide 3-kinase (PI3K), a lipid kinase that coordinates the intake and utilization of glucose, and mTOR, a kinase downstream of PI3K that stimulates transcription and translation. When chronically activated, the PI3K pathway can drive malignant transformation. Here, we discuss the insulin-PI3K signalling cascade and emphasize its roles in normal cells (including coordinating cell metabolism and growth), highlighting the features of this network that make it ideal for co-option by cancer cells. Furthermore, we discuss how this signalling network can affect therapeutic responses and how novel metabolic-based strategies might enhance treatment efficacy for cancer.


Assuntos
Sistema Endócrino/metabolismo , Insulina/metabolismo , Neoplasias/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Animais , Evolução Biológica , Humanos , Transdução de Sinais
17.
Ecotoxicol Environ Saf ; 195: 110496, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32213369

RESUMO

The impact of progestins (i.e. synthetic forms of progesterone) on aquatic organisms has drawn increasing attention due to their widespread occurrence in the aquatic environments and potential effects on the endocrine system of fish. In this study, the effects of norethindrone (NET, a progestin) on the reproductive behavior, sex hormone production and transcriptional expressions were evaluated by exposing female zebrafish to NET at 0, 3.1, 36.2 and 398.6 ng L-1 for 60 days. Results showed that NET impaired the mating behaviors of female at 36.2 and 398.6 ng L-1 exhibited by males and increased the frequency of atretic follicular cells in the ovary exposed to NET at 398.6 ng L-1. As for sex hormones, plasma testosterone concentration in zebrafish increased, while estradiol concentration decreased. Up-regulation of genes (Npr, Mpra, Mprß, Fshß, Lß, Tshb, Nis and Dio2) was detected in the brain of fish exposed to NET at 398.6 ng L-1. The transcriptional levels of genes (Esr1, Vtg1, Ar, Cyp19a, Cyp11b and Ptgs2) were generally inhibited in the ovary of zebrafish by NET at 398.6 ng L-1. Moreover, the transcripts of genes (Vtg1, Esr1, Ar and Pgr) in the liver were reduced by NET at 36.2 and 398.6 ng L-1. Our findings suggest that NET can potentially diminish the of fish populations not only by damaging their reproductive organs, but also by altering their mating behavior through the changes in the expressions of genes responsible for the production of sex hormones.


Assuntos
Hormônios Esteroides Gonadais/sangue , Noretindrona/toxicidade , Ovário/efeitos dos fármacos , Comportamento Sexual Animal/efeitos dos fármacos , Transcrição Genética/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/fisiologia , Animais , Sistema Endócrino/efeitos dos fármacos , Feminino , Hormônios Esteroides Gonadais/genética , Masculino , Ovário/patologia , Progesterona/metabolismo , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/metabolismo
18.
Sci Total Environ ; 719: 137115, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32105999

RESUMO

Di (2-ethylhexyl) phthalate (DEHP) is one of the predominant plasticizer and an endocrine disrupting chemical occurring almost in all partitions of the environment. Though DEHP occur at lower concentration, reluctance arises due to their ability to disrupt endocrine system even lower concentration. In the present study, DEHP was assessed for degradation at minimal level (1-100 µg L-1) by a novel bacterial strain, Rhodococcus jostii PEVJ9. In the experimental design, significant variables were concentration of silver nitrate and DEHP, pH, temperature, time and agitation. Degradation without SAM-silver nanoparticles was 30-66% (predicted value = 30.8-66.8%, R2 = 99.7%) while, degradation in the presence of SAM-silver nanoparticles onto bacterial cells was 100% (predicted value = 98.4-102.1%, R2 = 99.6%) within 72 h. In short, this is the first report illustrating the experimental designs in biogenic synthesis of SAM-silver nanoparticles and enhanced degradation of DEHP at minimal level. The study overcomes poor bioavailability and assimilation of DEHP at lower concentration by the microbial population present in the environment. Thus, an efficient clean-up would prevent or minimize DEHP exposure at all trophic levels ranging from feminization of fishes to reproductive disorders in humans.


Assuntos
Nanopartículas Metálicas , Dietilexilftalato , Sistema Endócrino , Poluentes Ambientais , Prata
19.
Environ Int ; 137: 105552, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32059144

RESUMO

Swine farm wastewaters (SFWs) are generally discharged either directly into nearby rivers or into fish ponds as a source of fertilizer/food for aquaculture in China. SFWs contain various contaminants including steroid hormones. However, there is an extreme paucity of data on their effects in fish populations. Here we investigated the endocrine disrupting effects of SFWs in G. affinis from 2 rivers (7 sites) and 2 fish ponds (2 sites) receiving SFWs and a reference site in Guangdong Province, China. In this study, a total number of 3078 adult western mosquitofish (Gambusia affinis) were collected and the sex ratio was determined. In addition, secondary sexual characteristics were examined and the transcriptional levels of target genes were analyzed. The results showed the mosquitofish populations had a significant increase in male-to-female ratio from 7 sites (including 2 fish ponds) among the 9 sampling sites. The hemal spines of females were masculinized at most sites while the hemal spines of males were feminized at approximately half of the sites (including 2 fish ponds). Significant reduction in vitellogenin (Vtg) mRNA expression was observed in females from 2 sites (including RS7) while elevated Vtg mRNA expression was noticed in males from 2 sites along the rivers (including RS7). Redundancy analysis showed that androgens in the water samples were closely related with male-to-female ratio in the mosquitofish populations and the masculinized hemal spines of females. The findings from this study demonstrated that discharge of SFWs could result in occurrence of both masculinized females and feminized males in mosquitofish population.


Assuntos
Ciprinodontiformes , Disruptores Endócrinos/toxicidade , Sistema Endócrino , Águas Residuárias , Poluentes Químicos da Água , Animais , China , Ecossistema , Sistema Endócrino/efeitos dos fármacos , Feminino , Masculino , Suínos , Poluentes Químicos da Água/toxicidade
20.
Environ Pollut ; 261: 114060, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32045791

RESUMO

Evidence is emerging that environmental exposure to bisphenol S (BPS), a substitute for bisphenol A (BPA), to humans and wildlife is on the rise. However, research on the neurobehavioral effects of this endocrine disruptive chemical is still in its infancy. In this study, we aimed to investigate the effects of long-term exposure to environmentally relevant concentrations of BPS on recognition memory and its mechanism(s) of action, especially focusing on the glutamatergic/ERK/CREB pathway in the brain. Adult female zebrafish were exposed to the vehicle, 17ß-estradiol (E2, 1 µg/L), or BPS (1, 10 and 30 µg/L) for 120 days. Fish were then tested in the object recognition (OR), object placement (OP), and social recognition tasks (SR). Chronic exposure to E2 and 1 µg/L of BPS improved fish performance in OP task. This was associated with an up-regulation in the mRNA expression of several subtypes of metabotropic and ionotropic glutamate receptors, an increase in the phosphorylation levels of ERK1/2 and CREB, and an elevated transcript abundance of several immediate early genes involved in synaptic plasticity and memory formation. In contrast, the exposure to 10 and 30 µg/L of BPS attenuated fish performance in all recognition memory tasks. The impairment of these memory functions was associated with a marked down-regulation in the expression and activity of genes and proteins involved in glutamatergic/ERK/CREB signaling cascade. Collectively, our study demonstrated that the long-term exposure to BPS elicits hermetic effects on the recognition memory in zebrafish. Furthermore, the effect of BPS on the recognition memory seems to be mediated by the glutamatergic/ERK/CREB signaling pathway.


Assuntos
Compostos Benzidrílicos , Peixe-Zebra , Animais , Cognição , Sistema Endócrino , Feminino , Humanos , Fenóis , Sulfonas
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