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Sample records for active endocrine organ

  1. Endocrine-Active Pharmaceuticals: An Environmental Concern?

    EPA Science Inventory

    Recently, there has been growing interest in pharmaceuticals that are specifically designed to have endocrine activity, such as the estrogens used in birth control pills, exerting unintended effects on fish and other aquatic organisms. These pharmaceuticals may not be persistent...

  2. Endocrine activation in tachycardias.

    PubMed

    Lukac, P; Lukacova, S; Vigas, M; Hatala, R

    2001-01-01

    This article reviews the complex character of neuroendocrine response to paroxysmal tachycardia. While the endocrine influences in arrhythmogenesis are well perceived by the cardiologists, less attention has been paid to influence of tachycardia on neuroendocrine activation. However, this may significantly alter the clinical course of tachycardias and its responses to pharmacotherapeutic interventions. Main characteristics of hormones with direct relationship to cardiovascular system (ANP, AVP, catecholamines, angiotensin and others) are listed with description of regulation of their secretion and main biological effects, especially with regard to regulation of circulation. Changes in hemodynamics during tachycardia with accompanying changes in ANP, AVP renin-angiotensin-aldosterone system, sympatho-neural and sympatho-adrenal activation are reviewed. Further research and understanding require more complex approach and concentration on interrelationship of different regulatory hormones in tachycardia. (Fig. 2, Ref. 96.) PMID:11763674

  3. Adipose tissue as an endocrine organ.

    PubMed

    McGown, Christine; Birerdinc, Aybike; Younossi, Zobair M

    2014-02-01

    Obesity is one of the most important health challenges faced by developed countries and is increasingly affecting adolescents and children. Obesity is also a considerable risk factor for the development of numerous other chronic diseases, such as insulin resistance, type 2 diabetes, heart disease and nonalcoholic fatty liver disease. The epidemic proportions of obesity and its numerous comorbidities are bringing into focus the highly complex and metabolically active adipose tissue. Adipose tissue is increasingly being considered as a functional endocrine organ. This article discusses the endocrine effects of adipose tissue during obesity and the systemic impact of this signaling.

  4. Skeletal muscle: an endocrine organ.

    PubMed

    Pratesi, Alessandra; Tarantini, Francesca; Di Bari, Mauro

    2013-01-01

    Tropism and efficiency of skeletal muscle depend on the complex balance between anabolic and catabolic factors. This balance gradually deteriorates with aging, leading to an age-related decline in muscle quantity and quality, called sarcopenia: this condition plays a central role in physical and functional impairment in late life. The knowledge of the mechanisms that induce sarcopenia and the ability to prevent or counteract them, therefore, can greatly contribute to the prevention of disability and probably also mortality in the elderly. It is well known that skeletal muscle is the target of numerous hormones, but only in recent years studies have shown a role of skeletal muscle as a secretory organ of cytokines and other peptides, denominated myokines (IL6, IL8, IL15, Brain-derived neurotrophic factor, and leukaemia inhibitory factor), which have autocrine, paracrine, or endocrine actions and are deeply involved in inflammatory processes. Physical inactivity promotes an unbalance between these substances towards a pro-inflammatory status, thus favoring the vicious circle of sarcopenia, accumulation of fat - especially visceral - and development of cardiovascular diseases, type 2 diabetes mellitus, cancer, dementia and depression, according to what has been called "the diseasome of physical inactivity". PMID:23858303

  5. Endocrine activity of persistent organic pollutants accumulated in human silicone implants--Dosing in vitro assays by partitioning from silicone.

    PubMed

    Gilbert, Dorothea; Mayer, Philipp; Pedersen, Mikael; Vinggaard, Anne Marie

    2015-11-01

    Persistent organic pollutants (POPs) accumulated in human tissues may pose a risk for human health by interfering with the endocrine system. This study establishes a new link between actual human internal POP levels and the endocrine active dose in vitro, applying partitioning-controlled dosing from silicone to the H295R steroidogenesis assay: (1) Measured concentrations of POPs in silicone breast implants were taken from a recent study and silicone disks were loaded according to these measurements. (2) Silicone disks were transferred into H295R cell culture plates in order to control exposure of the adrenal cells by equilibrium partitioning. (3) Hormone production of the adrenal cells was measured as toxicity endpoint. 4-Nonylphenol was used for method development, and the new dosing method was compared to conventional solvent-dosing. The two dosing modes yielded similar dose-dependent hormonal responses of H295R cells. However, with the partitioning-controlled freely dissolved concentrations (Cfree) as dose metrics, dose-response curves were left-shifted by two orders of magnitude relative to spiked concentrations. Partitioning-controlled dosing of POPs resulted in up to 2-fold increases in progestagen and corticosteroid levels at Cfree of individual POPs in or below the femtomolar range. Silicone acted not only as source of the POPs but also as a sorption sink for lipophilic hormones, stimulating the cellular hormone production. Methodologically, the study showed that silicone can be used as reference partitioning phase to transfer in vivo exposure in humans (silicone implants) to in vitro assays (partition-controlled dosing). The main finding was that POPs at the levels at which they are found in humans can interfere with steroidogenesis in a human adrenocortical cell line. PMID:26264162

  6. Endocrine activities and cellular stress responses in the marsh frog Pelophylax ridibundus exposed to cobalt, zinc and their organic nanocomplexes.

    PubMed

    Falfushynska, Halina; Gnatyshyna, Lesya; Fedoruk, Olga; Sokolova, Inna M; Stoliar, Oksana

    2016-01-01

    Metal-containing materials are extensively used in industry, personal care products and medicine, and their release in the environment causes concern for the potential impacts on aquatic organisms. We assessed endocrine disrupting potential of N-vinyl-2-pyrrolidone-based nanoparticles (Me-PSs) containing cobalt (Co(2+)) or zinc (Zn(2+)), using the marsh frog Pelophylax ridibundus as a model. Adult males were exposed for 14 days to waterborne Co(2+) (50μg/L), Zn(2+) (100μg/L) or corresponding concentrations of Co-PS, Zn-PS, or parental polymeric compound (PS). The indices of thyroid activity, vitellogenesis, cytochrome P450-dependent monooxygenases activity (EROD) and cytotoxicity markers were evaluated. Exposure to Co(2+) led to the elevation of serum thyrotropin (TSH) and hepatic deiodinase activities accompanied by the up-regulation of EROD activity. In contrast, the action of the polymer-containing substances (Co-PS, Zn-PS and PS) as well as free Zn(2+) caused a prominent decrease of EROD activity and a decrease in serum cortisol and TSH concentrations. Exposures to Zn(2+), Zn-PS and PS upregulated vitellogenesis in males. All exposures except Co(2+) caused neurotoxicity as indicated by the depletion of cholinesterase. These results demonstrate toxicity of Co- and Zn-containing Me-PSs and their parental compounds (Zn(2+) and PS) in frogs and indicate distinct mechanisms of Co(2+) action. Broad disruption of the hormonal pathways and reduced capacity for organic xenobiotic detoxification may have deleterious impacts on amphibian populations from habitats exposed to metallorganic pollution. PMID:26624501

  7. Endocrine activities and cellular stress responses in the marsh frog Pelophylax ridibundus exposed to cobalt, zinc and their organic nanocomplexes.

    PubMed

    Falfushynska, Halina; Gnatyshyna, Lesya; Fedoruk, Olga; Sokolova, Inna M; Stoliar, Oksana

    2016-01-01

    Metal-containing materials are extensively used in industry, personal care products and medicine, and their release in the environment causes concern for the potential impacts on aquatic organisms. We assessed endocrine disrupting potential of N-vinyl-2-pyrrolidone-based nanoparticles (Me-PSs) containing cobalt (Co(2+)) or zinc (Zn(2+)), using the marsh frog Pelophylax ridibundus as a model. Adult males were exposed for 14 days to waterborne Co(2+) (50μg/L), Zn(2+) (100μg/L) or corresponding concentrations of Co-PS, Zn-PS, or parental polymeric compound (PS). The indices of thyroid activity, vitellogenesis, cytochrome P450-dependent monooxygenases activity (EROD) and cytotoxicity markers were evaluated. Exposure to Co(2+) led to the elevation of serum thyrotropin (TSH) and hepatic deiodinase activities accompanied by the up-regulation of EROD activity. In contrast, the action of the polymer-containing substances (Co-PS, Zn-PS and PS) as well as free Zn(2+) caused a prominent decrease of EROD activity and a decrease in serum cortisol and TSH concentrations. Exposures to Zn(2+), Zn-PS and PS upregulated vitellogenesis in males. All exposures except Co(2+) caused neurotoxicity as indicated by the depletion of cholinesterase. These results demonstrate toxicity of Co- and Zn-containing Me-PSs and their parental compounds (Zn(2+) and PS) in frogs and indicate distinct mechanisms of Co(2+) action. Broad disruption of the hormonal pathways and reduced capacity for organic xenobiotic detoxification may have deleterious impacts on amphibian populations from habitats exposed to metallorganic pollution.

  8. Influence of naturally occurring dissolved organic matter, colloids, and cations on nanofiltration of pharmaceutically active and endocrine disrupting compounds.

    PubMed

    Sadmani, A H M Anwar; Andrews, Robert C; Bagley, David M

    2014-12-01

    This study examined the rejection of selected pharmaceutically active (PhAC) and endocrine disrupting compounds (EDCs) when using nanofiltration as a function of naturally occurring dissolved organic matter (DOM), colloidal particles, cations and their interactions. Lake Ontario water served as a source of natural DOM and colloidal particles. PhAC/EDC rejection experiments were conducted using raw Lake Ontario water and Lake Ontario water that was pre-treated with either ultrafiltration to remove colloidal particles, or fluidized ion exchange resins to remove DOM. Additionally, the concentration of cations (Ca(2+), Mg(2+), and Na(+)) in the raw and pre-treated water matrices was varied. While ionic PhACs and EDCs exhibited high rejections from all the water matrices examined, neutral compounds were most effectively rejected in water containing DOM and no colloids, and least effectively rejected from colloid-containing water with increased cations but no DOM. The presence of DOM significantly improved compound rejection and the increase in cation concentration significantly decreased rejection. The presence of colloids had comparatively little effect except to mitigate the impact of increased cation concentration, apparently providing some cation-buffering capacity. The sequence in which constituents are removed from waters during treatment may significantly impact PhAC and EDC removal, especially of neutral compounds.

  9. The skeleton as an endocrine organ.

    PubMed

    DiGirolamo, Douglas J; Clemens, Thomas L; Kousteni, Stavroula

    2012-11-01

    Surprising new discoveries in the field of skeletal biology show that bone cells produce endocrine hormones that regulate phosphate and glucose homeostasis. In this Review, we examine the features of these new endocrine pathways and discuss their physiological importance in the context of our current understanding of energy metabolism and mineral homeostasis. Consideration of evolutionary and comparative biology provides clues that a key driving force for the emergence of these hormonal pathways was the development of a large, energy-expensive musculoskeletal system. Specialized bone cells also evolved and produced endocrine hormones to integrate the skeleton in global mineral and nutrient homeostasis. The recognition of bone as a true endocrine organ represents a fertile area for further research and should improve the diagnosis and treatment of metabolic diseases such as osteoporosis and diabetes mellitus.

  10. Skeletal muscle is an endocrine organ.

    PubMed

    Iizuka, Kenji; Machida, Takuji; Hirafuji, Masahiko

    2014-01-01

    Skeletal muscle plays a key role in postural retention as well as locomotion for maintaining the physical activities of human life. Skeletal muscle has a second role as an elaborate energy production and consumption system that influences the whole body's energy metabolism. Skeletal muscle is a specific organ that engenders a physical force, and exercise training has been known to bring about multiple benefits for human health maintenance and/or improvement. The mechanisms underlying the improvement of the human physical condition have been revealed: skeletal muscle synthesizes and secretes multiple factors, and these muscle-derived factors, so-called as myokines, exert beneficial effects on peripheral and remote organs. In this short review, we focus on the third aspect of skeletal muscle function - namely, the release of multiple types of myokines, which constitute a broad network for regulating the function of remote organs as well as skeletal muscle itself. We conclusively show that skeletal muscle is one of the endocrine organs and that understanding the mechanisms of production and secretion of myokines may lead to a new pharmacological approach for treatment of clinical disorders.

  11. Spatial and temporal patterns of endocrine active chemicals in small streams indicate differential exposure to aquatic organisms

    USGS Publications Warehouse

    Lee, K.E.; Barber, L.B.; Schoenfuss, H.L.

    2014-01-01

    Alkylphenolic chemicals (APCs) and hormones were measured six times from February through October 2007 in three Minnesota streams receiving wastewater to identify spatial and temporal patterns in concentrations and in estrogen equivalency. Fish were collected once during the study to evaluate endpoints indicative of endocrine disruption. The most commonly detected APCs were 4-tert-octylphenol and 4-nonylphenol and the most commonly detected hormones were estrone and androstenedione. Chemical concentrations were greatest for nonylphenol ethoxycarboxylates (NPECs) (5,000-140,000 ng/l), followed by 4-nonlylphenol and 4-nonylphenolethoxylates (50-880 ng/l), 4-tert-octylphenol and 4-tert-octylphenolethoxylates with concentrations as great as 130 ng/l, and hormones (0.1-54 ng/l). Patterns in chemicals and estrogen equivalency indicated that wastewater effluent is a pathway of APCs and hormones to downstream locations in this study. However, upstream contributions can be equally or more important indicating alternative sources. This study indicates that aquatic organisms experience both spatially and temporally variable exposures in the number of compounds, total concentrations, and estrogenicity. This variability was evident in fish collected from the three rivers as no clear upstream to downstream pattern of endocrine disruption endpoints emerged.

  12. The heart as an endocrine organ.

    PubMed

    Ogawa, Tsuneo; de Bold, Adolfo J

    2014-01-01

    The concept of the heart as an endocrine organ arises from the observation that the atrial cardiomyocytes in the mammalian heart display a phenotype that is partly that of endocrine cells. Investigations carried out between 1971 and 1983 characterised, by virtue of its natriuretic properties, a polypeptide referred to atrial natriuretic factor (ANF). Another polypeptide isolated from brain in 1988, brain natriuretic peptide (BNP), was subsequently characterised as a second hormone produced by the mammalian heart atria. These peptides were associated with the maintenance of extracellular fluid volume and blood pressure. Later work demonstrated a plethora of other properties for ANF and BNP, now designated cardiac natriuretic peptides (cNPs). In addition to the cNPs, other polypeptide hormones are expressed in the heart that likely act upon the myocardium in a paracrine or autocrine fashion. These include the C-type natriuretic peptide, adrenomedullin, proadrenomedullin N-terminal peptide and endothelin-1. Expression and secretion of ANF and BNP are increased in various cardiovascular pathologies and their levels in blood are used in the diagnosis and prognosis of cardiovascular disease. In addition, therapeutic uses for these peptides or related substances have been found. In all, the discovery of the endocrine heart provided a shift from the classical functional paradigm of the heart that regarded this organ solely as a blood pump to one that regards this organ as self-regulating its workload humorally and that also influences the function of several other organs that control cardiovascular function.

  13. Bone Regulates Glucose Metabolism as an Endocrine Organ through Osteocalcin.

    PubMed

    Shao, Jin; Wang, Zhi; Yang, Tieyi; Ying, Hui; Zhang, Yan; Liu, Shuyi

    2015-01-01

    Skeleton was considered as a dynamic connective tissue, which was essential for mobility, calcium homeostasis, and hematopoietic niche. However more and more evidences indicate that skeleton works not only as a structural scaffold but also as an endocrine organ, which regulates several metabolic processes. Besides osteoprotegerin (OPG), sclerostin (SOST), and Dickopf (DKK) which play essential roles in bone formation, modelling, remodelling, and homeostasis, bone can also secret hormones, such as osteocalcin (OCN), which promotes proliferation of β cells, insulin secretion, and insulin sensitivity. Additionally OCN can also regulate the fat cells and male gonad endocrine activity and be regulated by insulin and the neural system. In summary, skeleton has endocrine function via OCN and plays an important role in energy metabolism, especially in glucose metabolism. PMID:25873961

  14. Potency matters: thresholds govern endocrine activity.

    PubMed

    Borgert, Christopher J; Baker, Stephen P; Matthews, John C

    2013-10-01

    Whether thresholds exist for endocrine active substances and for endocrine disrupting effects of exogenous chemicals has been posed as a question for regulatory policy by the European Union. This question arises from a concern that the endocrine system is too complex to allow estimations of safe levels of exposure to any chemical with potential endocrine activity, and a belief that any such chemical can augment, retard, or disrupt the normal background activity of endogenous hormones. However, vital signaling functions of the endocrine system require it to continuously discriminate the biological information conveyed by potent endogenous hormones from a more concentrated background of structurally similar, endogenous molecules with low hormonal potential. This obligatory ability to discriminate important hormonal signals from background noise can be used to define thresholds for induction of hormonal effects, without which normal physiological functions would be impossible. From such thresholds, safe levels of exposure can be estimated. This brief review highlights how the fundamental principles governing hormonal effects - affinity, efficacy, potency, and mass action - dictate the existence of thresholds and why these principles also define the potential that exogenous chemicals might have to interfere with normal endocrine functioning.

  15. Developing brain as an endocrine organ: secretion of dopamine.

    PubMed

    Ugrumov, Michael V; Saifetyarova, Julia Y; Lavrentieva, Antonina V; Sapronova, Anna Y

    2012-01-01

    This study was aimed to test our hypothesis that the developing brain operates as an endocrine organ before the establishment of the blood-brain barrier (BBB), in rats up to the first postnatal week. Dopamine (DA) was selected as a marker of the brain endocrine activity. The hypothesis was supported by the observations in rats of: (i) the physiological concentration of DA in peripheral blood of fetuses and neonates, before the BBB establishment, and its drop by prepubertal period, after the BBB development; (ii) a drop of the DA concentration in the brain for 54% and in blood for 74% on the 3rd postnatal day after the intraventricular administration of 50 μg of α-methyl-p-tyrosine, an inhibitor of DA synthesis, with no changes in the DA metabolism in peripheral DA-producing organs. Thus, the developing brain is a principal source of circulating DA which is capable of providing an endocrine regulation of peripheral organs and the brain.

  16. EADB: An Estrogenic Activity Database for Assessing Potential Endocrine Activity

    EPA Science Inventory

    Endocrine-active chemicals can potentially have adverse effects on both humans and wildlife. They can interfere with the body’s endocrine system through direct or indirect interactions with many protein targets. Estrogen receptors (ERs) are one of the major targets, and many ...

  17. Adipose tissue as an endocrine organ.

    PubMed

    Galic, Sandra; Oakhill, Jon S; Steinberg, Gregory R

    2010-03-25

    Obesity is characterized by increased storage of fatty acids in an expanded adipose tissue mass and is closely associated with the development of insulin resistance in peripheral tissues such as skeletal muscle and the liver. In addition to being the largest source of fuel in the body, adipose tissue and resident macrophages are also the source of a number of secreted proteins. Cloning of the obese gene and the identification of its product, leptin, was one of the first discoveries of an adipocyte-derived signaling molecule and established an important role for adipose tissue as an endocrine organ. Since then, leptin has been found to have a profound role in the regulation of whole-body metabolism by stimulating energy expenditure, inhibiting food intake and restoring euglycemia, however, in most cases of obesity leptin resistance limits its biological efficacy. In contrast to leptin, adiponectin secretion is often diminished in obesity. Adiponectin acts to increase insulin sensitivity, fatty acid oxidation, as well as energy expenditure and reduces the production of glucose by the liver. Resistin and retinol binding protein-4 are less well described. Their expression levels are positively correlated with adiposity and they are both implicated in the development of insulin resistance. More recently it has been acknowledged that macrophages are an important part of the secretory function of adipose tissue and the main source of inflammatory cyokines, such as TNFalpha and IL-6. An increase in circulating levels of these macrophage-derived factors in obesity leads to a chronic low-grade inflammatory state that has been linked to the development of insulin resistance and diabetes. These proteins commonly known as adipokines are central to the dynamic control of energy metabolism, communicating the nutrient status of the organism with the tissues responsible for controlling both energy intake and expenditure as well as insulin sensitivity. PMID:19723556

  18. Endocrine active chemicals and endocrine disruption in Minnesota streams and lakes: implications for aquatic resources, 1994-2008

    USGS Publications Warehouse

    Lee, Kathy E.; Schoenfuss, Heiko L.; Barber, Larry B.; Writer, Jeff H.; Blazer, Vicki; Keisling, Richard L.; Ferrey, Mark L.

    2010-01-01

    Although these studies indicate that wastewater-treatment plant effluent is a conduit for endocrine active chemicals to surface waters, endocrine active chemicals also were present in surface waters with no obvious wastewater-treatment plant effluent sources. Endocrine active chemicals were detected and indicators of endocrine disruption in fish were measured at numerous sites upstream from discharge of wastewater-treatment plant effluent. These observations indicate that other unidentified sources of endocrine active chemicals exist, such as runoff from land surfaces, atmospheric deposition, inputs from onsite septic systems, or other groundwater sources. Alternatively, some endocrine active chemicals may not yet have been identified or measured. The presence of biological indicators of endocrine disruption in male fish indicates that the fish are exposed to endocrine active chemicals. However indicators of endocrine disruption in male fish does not indicate an effect on fish reproduction or changes in fish populations.

  19. Developing brain as an endocrine organ: a paradoxical reality.

    PubMed

    Ugrumov, M V

    2010-06-01

    The maintaining of homeostasis in the organism in response to a variable environment is provided by the highly hierarchic neuroendocrine-immune system. The crucial component of this system is the hypothalamus providing the endocrine regulation of key peripheral organs, and the adenohypophysis. In this case, neuron-derived signaling molecules (SM) are delivered to the blood vessels in hypothalamic "neurohaemal organs" lacking the blood-brain barrier (BBB), the posterior lobe of the pituitary and the median eminence. The release of SM to the blood vessels in most other brain regions is prohibited by BBB. According to the conventional concept, the development of the neuroendocrine system in ontogenesis begins with the "maturation" of peripheral endocrine glands which first are self-governed and then operate under the adenohypophysial control. Meantime, the brain maturation is under the control of SM secreted by endocrine glands of the developing organism and coming from the placenta and maternal organism. The hypothalamus is involved in the neuroendocrine regulation only after its full maturation that is followed by the conversion of the opened-looped neuroendocrine system to the closed-looped system as in adulthood. Neurons of the developing brain begin to secrete SM shortly after their origin and long before the establishment of specific interneuronal relations providing initially autocrine and paracrine morphogenetic influence on differentiating target neurons. Taking into account that the brain lacks BBB over this ontogenetic period, we hypothesized that it operates as the multipotent endocrine gland secreting SM to the general circulation and thereby providing the endocrine regulation of peripheral organs and the brain. The term "multipotent" means that the spectrum of the brain-derived circulating SM and their occupancy at the periphery in the developing organism should greatly exceed those in adulthood. In order to test this hypothesis, gonadotropin

  20. [The heart as an endocrine organ].

    PubMed

    Mezősi, Emese; Bajnok, László; Tóth, Kálmán

    2012-12-23

    The discovery of cardiac hormone production significantly changed the evaluation of the function of the heart, which is rather regarded as a determining factor of the electrolyte and hemodynamic homeostasis cooperating with other organ systems instead of a mechanical pump. The most important hormones produced by the heart are the natriuretic peptides that have the primary role of protection against volume overload through natriuretic, diuretic, vasodilator and antiproliferative effects. They are integrative markers of the cardiac, vascular and renal functions and marking cardiorenal distress. Brain natriuretic peptide and the N-terminal pro-hormone (NT-proBNP) became generally accepted markers of heart failure exceeding traditional pathophysiological significance of those. They are useful in the diagnosis, estimation of prognosis and therapy guidance and their therapeutic administration is also available. Although the detection of extraadrenal aldosterone production is an exciting new discovery, intracardial aldosterone production is not significant in human beings. The intracardial thyroid hormone production is regulated by deiodinase activity. The role of elevated T3 concentration was suggested in the development of cardiac hypertrophy, while low T3 is assumed to be important in adaptation to hypoxia. An unexpected, complex relation can be determined between epicardial adipose tissue and coronary artery diseases, cytokine and adipokine production of adipocytes might be a part of the self-enhancing process of atherosclerosis.

  1. Carcinoma of endocrine organs: results of the RARECARE project.

    PubMed

    van der Zwan, Jan Maarten; Mallone, Sandra; van Dijk, Boukje; Bielska-Lasota, Magdalena; Otter, Renée; Foschi, Roberto; Baudin, Eric; Links, Thera P

    2012-09-01

    The rarity or the asymptomatic character of endocrine tumours results in a lack of epidemiological studies on their incidence and survival patterns. The aim of this study was to describe the incidence, prevalence and survival of endocrine tumours using a large database, which includes cancer patients diagnosed from 1978 to 2002, registered in 89 population-based cancer registries (CRs) with follow-up until 31st December 2003. These data give an unique overview of the burden of endocrine carcinomas in Europe. A list of tumour entities based on the third International Classification of Diseases for Oncology was provided by the project Surveillance of rare cancer in Europe (RARECARE) project. Over 33,594 cases of endocrine carcinomas were analysed in this study. Incidence rates increased with age and were highest in patients 65 years of age or older. In 2003, more than 315,000 persons in the EU (27 countries) were alive with a past diagnosis of a carcinoma of endocrine organs. The incidence of pituitary carcinoma equalled four per 1,000,000 person years and showed the strongest decline in survival with increasing age. Thyroid cancer showed the highest crude incidence rates (four per 100,000 person years) and was the only entity with a gender difference: (female-to-male ratio: 2:9). Parathyroid carcinoma was the rarest endocrine entity with two new cases per 10,000,000 person years. For adrenal carcinoma, the most remarkable observations were a higher survival for women compared to men (40% compared to 32%, respectively) and a particularly low relative survival of 24% in patients 65 years of age or older. More high quality studies on rare cancers, with additional information, e.g. on stage and therapeutic approach, are needed and may be of help in partly explaining the observed variation in survival.

  2. Adipose tissues as endocrine target organs.

    PubMed

    Lanthier, Nicolas; Leclercq, Isabelle A

    2014-08-01

    In the context of obesity, white adipocyte hypertrophy and adipose tissue macrophage infiltration result in the production of pro-inflammatory adipocytokines inducing insulin resistance locally but also in distant organs and contributing to low grade inflammatory status associated with the metabolic syndrome. Visceral adipose tissue is believed to play a prominent role. Brown and beige adipose tissues are capable of energy dissipation, but also of cytokine production and their role in dysmetabolic syndrome is emerging. This review focuses on metabolic and inflammatory changes in these adipose depots and contribution to metabolic syndrome. Also we will review surgical and pharmacological procedures to target adiposity as therapeutic interventions to treat obesity-associated disorders.

  3. Endocrine activity of mycotoxins and mycotoxin mixtures.

    PubMed

    Demaegdt, Heidi; Daminet, Britt; Evrard, Annick; Scippo, Marie-Louise; Muller, Marc; Pussemier, Luc; Callebaut, Alfons; Vandermeiren, Karine

    2016-10-01

    Reporter gene assays incorporating nuclear receptors (estrogen, androgen, thyroid β and PPARγ2) have been implemented to assess the endocrine activity of 13 mycotoxins and their mixtures. As expected, zearalenone and its metabolites α-zearalenol and β- zearalenol turned out to have the strongest estrogenic potency (EC50 8,7 10-10 ± 0,8; 3,1 10-11 ± 0,5 and 1,3 10-8 ± 0,3 M respectively). The metabolite of deoxynivalenol, 3-acetyl-deoxynivalenol also had estrogenic activity (EC50 3,8 10-7 ± 1,1 M). Furthermore, most of the mycotoxins (and their mixtures) showed anti-androgenic effects (15-acetyldeoxynivalenol, 3-acetyl-deoxynivalenol and α-zearalenol with potencies within one order of magnitude of that of the reference compound flutamide). In particular, deoxynivalenol and 15-acetyl-deoxynivalenol acted as antagonists for the PPARy2 receptor. When testing mixtures of mycotoxins on the same cell systems, we showed that most of the mixtures reacted as predicted by the concentration addition (CA) theory. Generally, the CA was within the 95% confidence interval of the observed ones, only minor deviations were detected. Although these reporter gene tests cannot be directly extrapolated in vivo, they can be the basis for further research. Especially the additive effects of ZEN and its metabolites are of importance and could have repercussions in vivo. PMID:27481073

  4. Endocrine activity of mycotoxins and mycotoxin mixtures.

    PubMed

    Demaegdt, Heidi; Daminet, Britt; Evrard, Annick; Scippo, Marie-Louise; Muller, Marc; Pussemier, Luc; Callebaut, Alfons; Vandermeiren, Karine

    2016-10-01

    Reporter gene assays incorporating nuclear receptors (estrogen, androgen, thyroid β and PPARγ2) have been implemented to assess the endocrine activity of 13 mycotoxins and their mixtures. As expected, zearalenone and its metabolites α-zearalenol and β- zearalenol turned out to have the strongest estrogenic potency (EC50 8,7 10-10 ± 0,8; 3,1 10-11 ± 0,5 and 1,3 10-8 ± 0,3 M respectively). The metabolite of deoxynivalenol, 3-acetyl-deoxynivalenol also had estrogenic activity (EC50 3,8 10-7 ± 1,1 M). Furthermore, most of the mycotoxins (and their mixtures) showed anti-androgenic effects (15-acetyldeoxynivalenol, 3-acetyl-deoxynivalenol and α-zearalenol with potencies within one order of magnitude of that of the reference compound flutamide). In particular, deoxynivalenol and 15-acetyl-deoxynivalenol acted as antagonists for the PPARy2 receptor. When testing mixtures of mycotoxins on the same cell systems, we showed that most of the mixtures reacted as predicted by the concentration addition (CA) theory. Generally, the CA was within the 95% confidence interval of the observed ones, only minor deviations were detected. Although these reporter gene tests cannot be directly extrapolated in vivo, they can be the basis for further research. Especially the additive effects of ZEN and its metabolites are of importance and could have repercussions in vivo.

  5. The past 10 years-new hormones, new functions, new endocrine organs.

    PubMed

    Bouillon, Roger; Drucker, Daniel J; Ferrannini, Ele; Grinspoon, Steven; Rosen, Clifford J; Zimmet, Paul

    2015-11-01

    Since the publication of the first issue of this journal in November 2005, our understanding of the endocrine system has evolved, with the identification of novel hormones and novel endocrine roles for previously identified molecules. Here, we have asked six of our Advisory Board Members to comment on how these insights have led to the recognition that many organs and tissues that were not widely considered part of the classic endocrine system in the past have important endocrine functions.

  6. Effects of Two Endocrine-active Pharmaceuticals, Tamoxifen and Anastrozole, on Reproduction in a Marine Fish, Tautogolabrus adspersus

    EPA Science Inventory

    Endocrine-active pharmaceuticals entering the aquatic environment through sewage effluent may have unintended, adverse impacts on the reproduction of aquatic organisms, which in turn may affect the sustainability of exposed populations. Laboratory experiments were conducted with ...

  7. Fate of steroid hormones and endocrine activities in swine manure disposal and treatment facilities.

    PubMed

    Combalbert, Sarah; Bellet, Virginie; Dabert, Patrick; Bernet, Nicolas; Balaguer, Patrick; Hernandez-Raquet, Guillermina

    2012-03-01

    Manure may contain high concern endocrine-disrupting compounds (EDCs) such as steroid hormones, naturally produced by pigs, which are present at μgL(-1) levels. Manure may also contain other EDCs such as nonylphenols (NP), polycyclic aromatic hydrocarbons (PAHs) and dioxins. Thus, once manure is applied to the land as soil fertilizer these compounds may reach aquifers and consequently living organisms, inducing abnormal endocrine responses. In France, manure is generally stored in anaerobic tanks prior spreading on land; when nitrogen removal is requested, manure is treated by aerobic processes before spreading. However, little is known about the fate of hormones and multiple endocrine-disrupting activities in such manure disposal and treatment systems. Here, we determined the fate of hormones and diverse endocrine activities during manure storage and treatment by combining chemical analysis and in vitro quantification of estrogen (ER), aryl hydrocarbon (AhR), androgen (AR), pregnane-X (PXR) and peroxysome proliferator-activated γ (PPARγ) receptor-mediated activities. Our results show that manure contains large quantities of hormones and activates ER and AhR, two of the nuclear receptors studied. Most of these endocrine activities were found in the solid fraction of manure and appeared to be induced mainly by hormones and other unidentified pollutants. Hormones, ER and AhR activities found in manure were poorly removed during manure storage but were efficiently removed by aerobic treatment of manure.

  8. A critical review finds styrene lacks direct endocrine disruptor activity.

    PubMed

    Gelbke, Heinz-Peter; Banton, Marcy; Leibold, Edgar; Pemberton, Mark; Samson, Susan Leanne

    2015-01-01

    The European Commission lists styrene (S) as an endocrine disruptor based primarily on reports of increased prolactin (PRL) levels in S-exposed workers. The US Environmental Protection Agency included S in its list of chemicals to be tested for endocrine activity. Therefore, the database of S for potential endocrine activity is assessed. In vitro and in vivo screening studies, as well as non-guideline and guideline investigations in experimental animals indicate that S is not associated with (anti)estrogenic, (anti)androgenic, or thyroid-modulating activity or with an endocrine activity that may be relevant for the environment. Studies in exposed workers have suggested elevated PRL levels that have been further examined in a series of human and animal investigations. While there is only one definitively known physiological function of PRL, namely stimulation of milk production, many normal stress situations may lead to elevations without any chemical exposure. Animal studies on various aspects of dopamine (DA), the PRL-regulating neurotransmitter, in the central nervous system did not give mechanistic explanations on how S may affect PRL levels. Overall, a neuroendocrine disruption of PRL regulation cannot be deduced from a large experimental database. The effects in workers could not consistently be reproduced in experimental animals and the findings in humans represented acute reversible effects clearly below clinical and pathological levels. Therefore, unspecific acute workplace-related stress is proposed as an alternative mode of action for elevated PRL levels in workers. PMID:26406562

  9. Adipose tissue: from lipid storage compartment to endocrine organ.

    PubMed

    Scherer, Philipp E

    2006-06-01

    Adipose tissue, when carried around in excessive amounts, predisposes to a large number of diseases. Epidemiological data show that the prevalence of obesity has significantly increased over the past 20 years and continues to do so at an alarming rate. Here, some molecular aspects of the key constituent of adipose tissue, the adipocyte, are reviewed. While the adipocyte has been studied for many years and remarkable insights have been gained about some processes, many areas of the physiology of the fat cell remain unexplored. Our understanding of how cellular events in the adipocyte affect the local environment through paracrine interactions and how systemic effects are achieved through endocrine interactions is rudimentary. While storage and release of lipids are major functions of adipocytes, the adipocyte also uses specific lipid molecules for intracellular signaling and uses a host of protein factors to communicate with essentially every organ system in the body. The intensity and complexity of these signals are highly regulated, differ in each fat pad, and are dramatically affected by various disease states. PMID:16731815

  10. [Adipose tissue as an endocrine organ: role in pathogenesis of ischemic heart disease and insulin independent diabetes mellitus].

    PubMed

    Lapchyns'ka, I I; Stefaniuk, M F

    2002-01-01

    Obesity is a risk factor for cardiovascular morbidity and mortality. The present review of the modern literature is devoted to the problem of regarding the adipose tissue as not only a repository of energy supplies but an active endocrine organ as well whose activity exerts a definite effect on the function of many bodily systems. Specific emphasis is directed toward aspects of the function of certain secretory proteins involved in the process of the arterial pressure regulation and/or organs injuring.

  11. Endocrine disruptor activity of multiple environmental food chain contaminants.

    PubMed

    Wielogórska, E; Elliott, C T; Danaher, M; Connolly, L

    2015-02-01

    Industrial chemicals, antimicrobials, drugs and personal care products have been reported as global pollutants which enter the food chain. Some of them have also been classified as endocrine disruptors based on results of various studies employing a number of in vitro/vivo tests. The present study employed a mammalian reporter gene assay to assess the effects of known and emerging contaminants on estrogen nuclear receptor transactivation. Out of fifty-nine compounds assessed, estrogen receptor agonistic activity was observed for parabens( n = 3), UV filters (n = 6), phthalates (n = 4) and a metabolite, pyrethroids (n = 9) and their metabolites (n = 3). Two compounds were estrogen receptor antagonists while some of the agonists enhanced 17b-estradiol mediated response.This study reports five new compounds (pyrethroids and their metabolites) possessing estrogen agonist activity and highlights for the first time that pyrethroid metabolites are of particular concern showing much greater estrogenic activity than their parent compounds.

  12. Influence of metabolism on endocrine activities of bisphenol S.

    PubMed

    Skledar, Darja Gramec; Schmidt, Jan; Fic, Anja; Klopčič, Ivana; Trontelj, Jurij; Dolenc, Marija Sollner; Finel, Moshe; Mašič, Lucija Peterlin

    2016-08-01

    Bisphenol S (BPS; bis[4-hydroxyphenyl]sulfone) is commonly used as a replacement for bisphenol A in numerous consumer products. The main goal of this study was to examine the influence of different metabolic reactions that BPS undergoes on the endocrine activity. We demonstrate that hydroxylation of the aromatic ring of BPS, catalyzed mainly by the cytochrome P450 enzymes CYP3A4 and CYP2C9, is its major in-vitro phase I biotransformation. Nevertheless, coupled oxidative-conjugative reactions analyses revealed that glucuronidation and formation of BPS glucuronide is the predominant BPS metabolic pathway. BPS reactive metabolites that can be tracked as glutathione conjugates were not detected in the present study. Two in-vitro systems were used to evaluate the endocrine activity of BPS and its two main metabolites, BPS glucuronide and hydroxylated BPS 4-(4-hydroxy-benzenesulfonyl)-benzene-1,2-diol (BPSM1). In addition, we have tested two structural analogs of BPS, bis[4-(2-hydroxyetoxy)phenyl]sulfone (BHEPS) and 4,4-sulfonylbis(2-methylphenol) (dBPS). The test systems were yeast cells, for evaluating estrogenic and androgenic activities, and the GH3.TRE-Luc reporter cell line for measuring thyroid hormone activity. BPS and BPSM1 were weak agonists of the estrogen receptor, EC50 values of 8.4 × 10(-5) M and 6.7 × 10(-4) M, respectively. Additionally, BPSM1 exhibited weak antagonistic activity toward the thyroid hormone receptor, with an IC50 of 4.3 × 10(-5) M. In contrast to BPSM1, BPS glucuronide was inactive in these assays, inhibiting neither the estrogen nor the thyroid hormone receptors. Hence, glucuronidation appears to be the most important pathway for both BPS metabolism and detoxification.

  13. Prosobranch snails as test organisms for the assessment of endocrine active chemicals--an overview and a guideline proposal for a reproduction test with the freshwater mudsnail Potamopyrgus antipodarum.

    PubMed

    Duft, Martina; Schmitt, Claudia; Bachmann, Jean; Brandelik, Cornelius; Schulte-Oehlmann, Ulrike; Oehlmann, Jörg

    2007-02-01

    Recently, prosobranch snails have been recommended as promising candidates for test organisms for the assessment of endocrine active chemicals. Three prosobranch snail species, the freshwater mudsnail Potamopyrgus antipodarum, the freshwater ramshorn snail Marisa cornuarietis, and the marine netted whelk Nassarius reticulatus are portrayed and their respective biotests are presented together with results of laboratory experiments and biological effect monitoring surveys in the field. All characterized species are highly sensitive toward xeno-androgens [triphenyltin (TPT), tributyltin (TBT), methyltestosterone (MT) and fenarimol (FEN)], and xeno-estrogens [bisphenol A (BPA), octylphenol (OP), ethinylestradiol], and show effects at environmentally relevant, rather low concentrations in laboratory experiments. For exposure to the xeno-androgen TPT, EC(10) values range between 15.9 and 29.0 ng as Sn/L (sediment 0.03 mug as Sn/kg), for TBT, EC(10) values are found between 3.42 and 37.8 ng as Sn/L (sediment 2.98 microg as Sn/kg) and effect concentrations for FEN are calculated as 18.6 ng/L (EC(10)) and 0.19 microg/kg (EC(50) sediment; EC(10) not calculable). Exposure to xeno-estrogens yielded EC(10 )values of 13.9 ng/L (0.19 microg/kg) for BPA, a NOEC of <1 microg/L (EC(10) of 0.004 microg/kg) for OP and a NOEC of 1 ng/l (EC(10) sediment of 2.2 microg/kg) for ethinylestradiol. Responses to androgens comprised the development of imposex and the reduction of fertility or embryo production, effects of estrogens included the stimulation of egg production and embryo production, and the increased weight of glands. Also, biological effect monitoring studies with P. antipodarum and N. reticulatus in several rivers or estuarine areas revealed the capacity of the biotests to detect an androgenic or estrogenic potential of sediment samples. A comparison of the three test species with regard to sensitivity and practical aspects in routine application favors the freshwater mudsnail P

  14. Remote preconditioning-endocrine factors in organ protection against ischemic injury.

    PubMed

    Bolte, Craig S; Liao, Siyun; Gross, Garrett J; Schultz, Jo El J

    2007-09-01

    Cardiovascular disease is the leading cause of death in the United States and developing world. Experimental and clinical studies have demonstrated that a number of interventions including brief periods of ischemia or hypoxia and certain endogenous factors such as opioids, bradykinin, growth factors or pharmacological agents are capable of protecting the heart against post-ischemic contractile dysfunction, arrhythmias and myocardial infarction. This conventional cardioprotection occurs via an autocrine or paracrine action in which these protective factors are released from the heart to act upon itself. Over the last ten years, a growing body of evidence indicates that a brief ischemic insult on one organ releases endogenous factors that protect other organs against a prolonged ischemic insult. This phenomenon, termed remote preconditioning or preconditioning at a distance, implicates an endocrine action, and may involve humoral or neural-endocrine signaling. This review will summarize the endocrine factors identified and implicated in this inter-organ cytoprotection. PMID:17897043

  15. The Gut Microbial Endocrine Organ: Bacterially-Derived Signals Driving Cardiometabolic Diseases

    PubMed Central

    Brown, J. Mark; Hazen, Stanley L.

    2015-01-01

    The human gastrointestinal tract is home to trillions of bacteria, which vastly outnumber host cells in the body. Although generally overlooked in the field of endocrinology, gut microbial symbionts organize to form a key endocrine organ that convert nutritional cues from the environment into hormone-like signals that impact both normal physiology and chronic disease in the human host. Recent evidence suggests that several gut microbial-derived products are sensed by dedicated host receptor systems to alter cardiovascular disease (CVD) progression. In fact, gut microbial metabolism of dietary components results in the production of proatherogenic circulating factors that act through a meta-organismal endocrine axis to impact CVD risk. Whether pharmacological interventions at the level of the gut microbial endocrine organ will reduce CVD risk is a key new question in the field of cardiovascular medicine. Here we discuss the opportunities and challenges that lie ahead in targeting meta-organismal endocrinology for CVD prevention. PMID:25587655

  16. Skeletal muscle as an endocrine organ: PGC-1α, myokines and exercise

    PubMed Central

    Schnyder, Svenia; Handschin, Christoph

    2015-01-01

    An active lifestyle is crucial to maintain health into old age; inversely, sedentariness has been linked to an elevated risk for many chronic diseases. The discovery of myokines, hormones produced by skeletal muscle tissue, suggests the possibility that these might be molecular mediators of the whole body effects of exercise originating from contracting muscle fibers. Even though less is known about the sedentary state, the lack of contraction-induced myokines or the production of a distinct set of hormones in the inactive muscle could likewise contribute to pathological consequences in this context. In this review, we try to summarize the most recent developments in the study of muscle as an endocrine organ and speculate about the potential impact on our understanding of exercise and sedentary physiology, respectively. PMID:26453501

  17. Early outgrowth cells release soluble endocrine antifibrotic factors that reduce progressive organ fibrosis.

    PubMed

    Yuen, Darren A; Connelly, Kim A; Zhang, Yanling; Advani, Suzanne L; Thai, Kerri; Kabir, Golam; Kepecs, David; Spring, Christopher; Smith, Christopher; Batruch, Ihor; Kosanam, Hari; Advani, Andrew; Diamandis, Eleftherios; Marsden, Philip A; Gilbert, Richard E

    2013-11-01

    Adult bone marrow-derived cells can improve organ function in chronic disease models, ostensibly by the release of paracrine factors. It has, however, been difficult to reconcile this prevailing paradigm with the lack of cell retention within injured organs and their rapid migration to the reticuloendothelial system. Here, we provide evidence that the salutary antifibrotic effects of bone marrow-derived early outgrowth cells (EOCs) are more consistent with an endocrine mode of action, demonstrating not only the presence of antifibrotic factors in the plasma of EOC-treated rats but also that EOC conditioned medium (EOC-CM) potently attenuates both TGF-β- and angiotensin II-induced fibroblast collagen production in vitro. To examine the therapeutic relevance of these findings in vivo, 5/6 subtotally nephrectomized rats, a model of chronic kidney and heart failure characterized by progressive fibrosis of both organs, were randomized to receive i.v. injections of EOC-CM, unconditioned medium, or 10(6) EOCs. Rats that received unconditioned medium developed severe kidney injury with cardiac diastolic dysfunction. In comparison, EOC-CM-treated rats demonstrated substantially improved renal and cardiac function and structure, mimicking the changes found in EOC-treated animals. Mass spectrometric analysis of EOC-CM identified proteins that regulate cellular functions implicated in fibrosis. These results indicate that EOCs secrete soluble factor(s) with highly potent antifibrotic activity, that when injected intravenously replicate the salutary effects of the cells themselves. Together, these findings suggest that an endocrine mode of action may underlie the effectiveness of cell therapy in certain settings and portend the possibility for systemic delivery of cell-free therapy.

  18. MYSID CRUSTACEANS AS POTENTIAL TEST ORGANISMS FOR THE EVALUATION OF ENVIRONMENTAL ENDOCRINE DISRUPTORS: A REVIEW

    EPA Science Inventory

    Verslycke, Tim A., Nancy Fockedey, Charles L. McKenney, Jr., Stephen D. Roast, Malcolm B. Jones, Jan Mees and Colin R. Janssen. 2004. Mysid Crustaceans as Potential Test Organisms for the Evaluation of Environmental Endocrine Disruption: A Review. Environ. Toxicol. Chem. 23(5):12...

  19. ENDOCRINE ACTIVE SUBSTANCES AND DOSE-RESPONSE FOR INDIVIDUALS AND POPULATIONS

    EPA Science Inventory

    Endocrine Active Substances and Dose-Response for Individuals and Populations
    Hugh A. Barton

    Abstract for IUPAC-SCOPE article

    Dose-response characteristics for endocrine disruption have been major focuses in efforts to understand potential impacts on human and ec...

  20. Toxicity and Estrogenic Endocrine Disrupting Activity of Phthalates and Their Mixtures

    PubMed Central

    Chen, Xueping; Xu, Shisan; Tan, Tianfeng; Lee, Sin Ting; Cheng, Shuk Han; Lee, Fred Wang Fat; Xu, Steven Jing Liang; Ho, Kin Chung

    2014-01-01

    Phthalates, widely used in flexible plastics and consumer products, have become ubiquitous contaminants worldwide. This study evaluated the acute toxicity and estrogenic endocrine disrupting activity of butyl benzyl phthalate (BBP), di(n-butyl) phthalate (DBP), bis(2-ethylhexyl) phthalate (DEHP), diisodecyl phthalate (DIDP), diisononyl phthalate (DINP), di-n-octyl phthalate (DNOP) and their mixtures. Using a 72 h zebrafish embryo toxicity test, the LC50 values of BBP, DBP and a mixture of the six phthalates were found to be 0.72, 0.63 and 0.50 ppm, respectively. The other four phthalates did not cause more than 50% exposed embryo mortality even at their highest soluble concentrations. The typical toxicity symptoms caused by phthalates were death, tail curvature, necrosis, cardio edema and no touch response. Using an estrogen-responsive ChgH-EGFP transgenic medaka (Oryzias melastigma) eleutheroembryos based 24 h test, BBP demonstrated estrogenic activity, DBP, DEHP, DINP and the mixture of the six phthalates exhibited enhanced-estrogenic activity and DIDP and DNOP showed no enhanced- or anti-estrogenic activity. These findings highlighted the developmental toxicity of BBP and DBP, and the estrogenic endocrine disrupting activity of BBP, DBP, DEHP and DINP on intact organisms, indicating that the widespread use of these phthalates may cause potential health risks to human beings. PMID:24637910

  1. Toxicity and estrogenic endocrine disrupting activity of phthalates and their mixtures.

    PubMed

    Chen, Xueping; Xu, Shisan; Tan, Tianfeng; Lee, Sin Ting; Cheng, Shuk Han; Lee, Fred Wang Fat; Xu, Steven Jing Liang; Ho, Kin Chung

    2014-03-14

    Phthalates, widely used in flexible plastics and consumer products, have become ubiquitous contaminants worldwide. This study evaluated the acute toxicity and estrogenic endocrine disrupting activity of butyl benzyl phthalate (BBP), di(n-butyl) phthalate (DBP), bis(2-ethylhexyl) phthalate (DEHP), diisodecyl phthalate (DIDP), diisononyl phthalate (DINP), di-n-octyl phthalate (DNOP) and their mixtures. Using a 72 h zebrafish embryo toxicity test, the LC50 values of BBP, DBP and a mixture of the six phthalates were found to be 0.72, 0.63 and 0.50 ppm, respectively. The other four phthalates did not cause more than 50% exposed embryo mortality even at their highest soluble concentrations. The typical toxicity symptoms caused by phthalates were death, tail curvature, necrosis, cardio edema and no touch response. Using an estrogen-responsive ChgH-EGFP transgenic medaka (Oryzias melastigma) eleutheroembryos based 24 h test, BBP demonstrated estrogenic activity, DBP, DEHP, DINP and the mixture of the six phthalates exhibited enhanced-estrogenic activity and DIDP and DNOP showed no enhanced- or anti-estrogenic activity. These findings highlighted the developmental toxicity of BBP and DBP, and the estrogenic endocrine disrupting activity of BBP, DBP, DEHP and DINP on intact organisms, indicating that the widespread use of these phthalates may cause potential health risks to human beings.

  2. Removal of endocrine-disrupting chemicals in activated sludge treatment works.

    PubMed

    Johnson, A C; Sumpter, J P

    2001-12-15

    The release of endocrine-disrupting chemicals into the aquatic environment has raised the awareness of the central role played by sewage treatment in lowland water quality. This review focuses on the activated sludge process, which is commonly used to treat sewage in large towns and cities and which successfully removes the bulk of the organic compounds that enter the works. However, not all compounds are completely broken down or converted to biomass. For example, the estrogenic alkylphenols and steroid estrogens found in effluent are the breakdown products of incomplete breakdown of their respective parent compounds. Batch microcosm studies have indicated that estrone, ethinylestradiol, and alkylphenols will not be completely eliminated in activated sludge over typical treatment times. Field data suggest that the activated sludge treatment process can consistently remove over 85% of estradiol, estriol, and ethinylestradiol. The removal performance for estrone appears to be less and is more variable. Because of its relatively high hydrophobicity, the accumulation of alkylphenol in sludge has been observed. Although it has not been examined, accumulation of ethinylestradiol in sludge is a possibility due to its recalcitrance and hydrophobicity. A comparison between the concentrations of some of the major endocrine-active chemicals in effluents and their biological potencies has been made, to direct attention to the chemicals of most concern. While water purification techniques such as UV or activated charcoal could significantly remove these microorganic contaminants, the high costs involved suggest that research into the potential for treatment optimization should receive more attention. PMID:11775141

  3. Influence of endocrine active compounds on the developing rodent brain.

    PubMed

    Patisaul, Heather B; Polston, Eva K

    2008-03-01

    Changes in the volumes of sexually dimorphic brain nuclei are often used as a biomarker for developmental disruption by endocrine-active compounds (EACs). However, these gross, morphological analyses do not reliably predict disruption of cell phenotype or neuronal function. Therefore, an experimental approach that simultaneously assesses anatomical, physiological and behavioral endpoints is required when developing risk assessment models for EAC exposure. Using this more comprehensive approach we have demonstrated that the disruption of nuclear volume does not necessarily coincide with disruption of cellular phenotype or neuroendocrine function in two sexually dimorphic brain nuclei: the anteroventral periventricular nucleus of the hypothalamus (AVPV) and the sexually dimorphic nucleus of the preoptic area (SDN). These results demonstrate that nuclear volume is likely not an appropriate biomarker for EAC exposure. We further demonstrated that neonatal exposure to the EACs genistein (GEN) and Bisphenol-A (BPA) can affect sexually dimorphic brain morphology and neuronal phenotypes in adulthood with regional and cellular specificity suggesting that effects observed in one brain region may not be predictive of effects within neighboring regions. Finally, developmental EAC exposure has been shown to affect a variety of sexually dimorphic behaviors including reproductive behavior. These effects are likely to have a broad impact as maladaptive behavior could translate to decreased fitness of entire populations. Collectively, these findings emphasize the need to employ a comprehensive approach that addresses anatomical, functional and behavioral endpoints when evaluating the potential effects of EAC exposure.

  4. VEGF-targeted cancer therapeutics-paradoxical effects in endocrine organs.

    PubMed

    Cao, Yihai

    2014-09-01

    Systemic administration of antiangiogenic drugs that target components of the vascular endothelial growth factor A (VEGF-A; VEGF) signal transduction pathway has become a viable therapeutic option for patients with various types of cancer. Nevertheless, these drugs can drive alterations in healthy vasculatures, which in turn are associated with adverse effects in healthy tissues. VEGF is crucial for vascular homeostasis and the maintenance of vascular integrity and architecture in endocrine organs. Given these critical physiological functions, systemic delivery of drugs that target VEGF signalling can block VEGF-mediated vascular functions in endocrine organs, such as the thyroid gland, and lead to endocrine dysfunction, including hypothyroidism, adrenal insufficiency and altered insulin sensitivity. This Review discusses emerging evidence from preclinical and clinical studies that contributes to understanding the mechanisms that underlie the vascular changes and subsequent modulations of endocrine function that are induced by targeted inhibition of VEGF signalling. Understanding these mechanisms is crucial for the design of antiangiogenic drugs with minimal associated adverse effects that will enable effective treatment of patients with cancer.

  5. In vivo endocrine disruption assessment of wastewater treatment plant effluents with small organisms.

    PubMed

    Castillo, Luis; Seriki, Kemi; Mateos, Stéphanie; Loire, Nicolas; Guédon, Nathalie; Lemkine, Gregory F; Demeneix, Barbara A; Tindall, Andrew J

    2013-01-01

    Surface water receives a variety of micro-pollutants that could alter aquatic organisms' reproduction and development. It is known that a few nanograms per litre of these compounds can induce endocrine-disrupting effects in aquatic species. Many compounds are released daily in wastewater, and identifying the compounds responsible for inducing such disruption is difficult. Methods using biological analysis are therefore an alternative to chemical analysis, as the endocrine disruption potential of the stream as a whole is considered. To detect hormonal disruption of thyroid and oestrogenic functions, fluorescent Xenopus laevis tadpoles and medaka (Oryzias latipes) fish larvae bearing genetic constructs integrating hormonal responsive elements were used for physiological screens for potential endocrine disruption in streams from an urban wastewater treatment plant. The Xenopus model was used to assess thyroid disruption and the medaka model oestrogenic disruption in wastewater samples. Assays using the genetically modified organisms were conducted on 9 influent and 32 effluent samples. The thyroidal effect of wastewater was either reduced or removed by the treatment plant; no oestrogenic effect was detected in any of the wastewater samples. PMID:23823564

  6. Exposures, Mechanisms, and Impacts of Endocrine-Active Flame Retardants

    PubMed Central

    Dishaw, Laura; Macaulay, Laura; Roberts, Simon C.; Stapleton, Heather M.

    2014-01-01

    This review summarizes the endocrine and neurodevelopmental effects of two current-use additive flame retardants (FRs), tris (1,3-dichloro-isopropyl) phosphate (TDCPP) and Firemaster® 550 (FM 550), and the recently phased-out polybrominated diphenyl ethers (PBDEs), all of which were historically or are currently used in polyurethane foam applications. Use of these chemicals in consumer products has led to widespread exposure in indoor environments. PBDEs and their hydroxylated metabolites appear to primarily target the thyroid system, likely due to their structural similarity to endogenous thyroid hormones. In contrast, much less is known about the toxicity of TDCPP and FM550. However, recent in vitro and in vivo studies suggest that both should be considered endocrine disruptors as studies have linked TDCPP exposure with changes in circulating hormone levels, and FM 550 exposure with changes in adipogenic and osteogenic pathways. PMID:25306433

  7. The biological properties of aspartame. III. Examination for endocrine-like activities.

    PubMed

    Saunders, F J; Pautsch, W F; Nutting, E F

    1980-01-01

    A series of studies with aspartame were run in mice, rats and rabbits using standard procedures to characterize possible estrogenic, androgenic, progestational and glucocorticoid activities. Aspartame was administered orally at levels (ca 300 mg/kg/day) substantially in excess of expected maximal human intake when used as a sweetening agent. No significant hormone-mimetic response was observed in the endocrine target organs evaluated. In similar studies, when administered simultaneously with the steroid hormones, it did not reduce the response expected with the steroid. Thus, it was concluded that ingestion of aspartame should not produce any estrogenic, androgenic, progestational or glucocorticoid-like effects. Further, it should not alter the actions of the endogeneous steroid hormones.

  8. Hypothesis-driven weight of evidence analysis to determine potential endocrine activity of MTBE.

    PubMed

    de Peyster, Ann; Mihaich, Ellen

    2014-08-01

    Endocrine-related endpoints in animals have been reported to respond to high doses of methyl tertiary-butyl ether (MTBE), however, a systematic and transparent evaluation of endocrine potential has not been published. Resolving whether MTBE exhibits endocrine activity is important given regulatory and public interest in endocrine disrupting substances and their potential for causing adverse effects in humans or wildlife. A weight-of-evidence (WoE) analysis was conducted, focusing on hypotheses related to the potential for MTBE to interact with estrogen, androgen, and thyroid pathways, and steroidogenesis. To reach scientifically justified conclusions based on the totality of evidence, this WoE procedure involved a semi-quantitative relevance weighting of each endpoint for each hypothesis and systematic consideration of each endpoint in various study designs. This procedure maximized use of an extensive body of relevant and reliable literature on MTBE with evidence supporting or opposing a given mode of action hypothesis. Evaluating the strength and consistency of observations from many MTBE studies also provided a way to assess whether high doses used in experiments with MTBE confound identification of direct endocrine system responses. Based on results of studies using mammalian and fish models and in vitro screening assays, this WoE assessment reveals that MTBE lacks direct endocrine activity. PMID:24813373

  9. A consolidated method for screening the endocrine activity of drinking water.

    PubMed

    Chevolleau, Sylvie; Debrauwer, Laurent; Stroheker, Thomas; Viglino, Liza; Mourahib, Issam; Meireles, Maria-Helena; Grimaldi, Marina; Balaguer, Patrick; di Gioia, Lodovico

    2016-12-15

    Endocrine activity of drinking water is a matter of growing interest for scientists as well as health authorities. A concentration technique for endocrine activity screening was developed, optimized, and transposed from 200mL to 10L water samples. To avoid any contamination during concentration, the method was developed using exclusively glass, Teflon and stainless steel materials. Any potential losses were tracked using three model radiolabeled molecules, namely BPA, DEHP and 4n-NP. The final method allowed 10L water samples to be concentrated 5000-fold, with good recovery and repeatability. After validation, by concentrating spiked and non-spiked 10L samples of EVIAN natural mineral water, 14 different drinking water samples were concentrated and screened for endocrine disrupting activity using bioluminescent assays. Samples consisting of bottled water, conditioned in various materials (glass, PET) and subjected to different storage conditions, had no hormone-like activities whereas estrogenic activity was found in the filtered tap water.

  10. A consolidated method for screening the endocrine activity of drinking water.

    PubMed

    Chevolleau, Sylvie; Debrauwer, Laurent; Stroheker, Thomas; Viglino, Liza; Mourahib, Issam; Meireles, Maria-Helena; Grimaldi, Marina; Balaguer, Patrick; di Gioia, Lodovico

    2016-12-15

    Endocrine activity of drinking water is a matter of growing interest for scientists as well as health authorities. A concentration technique for endocrine activity screening was developed, optimized, and transposed from 200mL to 10L water samples. To avoid any contamination during concentration, the method was developed using exclusively glass, Teflon and stainless steel materials. Any potential losses were tracked using three model radiolabeled molecules, namely BPA, DEHP and 4n-NP. The final method allowed 10L water samples to be concentrated 5000-fold, with good recovery and repeatability. After validation, by concentrating spiked and non-spiked 10L samples of EVIAN natural mineral water, 14 different drinking water samples were concentrated and screened for endocrine disrupting activity using bioluminescent assays. Samples consisting of bottled water, conditioned in various materials (glass, PET) and subjected to different storage conditions, had no hormone-like activities whereas estrogenic activity was found in the filtered tap water. PMID:27451182

  11. COUP-TFII inhibits NFkappaB activation in endocrine-resistant breast cancer cells

    PubMed Central

    Litchfield, Lacey M.; Appana, Savitri N.; Datta, Susmita; Klinge, Carolyn M.

    2016-01-01

    Reduced COUP-TFII expression contributes to endocrine resistance in breast cancer cells. Endocrine-resistant breast cancer cells have higher NFkappa B (NFκB) activity and target gene expression. The goal of this study was to determine if COUP-TFII modulates NFκB activity. Endocrine-resistant LCC9 cells with low endogenous COUP-TFII displayed ~5-fold higher basal NFκB activity than parental endocrine-sensitive MCF-7 breast cancer cells. Transient transfection of LCC9 cells with COUP-TFII inhibited NFκB activation and reduced NFκB target gene expression. COUP-TFII and NFκB were inversely correlated in breast cancer patient samples. Endogenous COUP-TFII coimmunoprecipitated with NFκB subunits RelB and NFκB1 in MCF-7 cells. COUP-TFII inhibited NFκB-DNA binding in vitro and impaired coactivator induced NFκB transactivation. LCC9 cells were growth-inhibited by an NFκB inhibitor and 4-hydroxytamoxifen compared to MCF-7 cells. Together these data indicate a novel role for COUP-TFII in suppression of NFκB activity and explain, in part, why decreased COUP-TFII expression results in an endocrine-resistant phenotype. PMID:24141032

  12. Steroidogenic factor-1: its role in endocrine organ development and differentiation.

    PubMed

    Hammer, G D; Ingraham, H A

    1999-07-01

    The cloning of the first steroid hormone receptor over a decade ago provided vital insight into the mechanisms by which steroid hormones activate gene transcription. When bound by hormone, these receptors function as ligand-dependent transcription factors by binding to unique response elements in the promoter of specific target genes. Over 60 receptors have now been characterized in this superfamily of steroid receptors. Many receptors known as orphan receptors have been cloned by homology and have no known ligands but appear to be mediators of endocrine function in the adult and in many cases are essential developmental regulators in endocrine organogenesis. One such receptor is steroidogenic factor-1 (SF-1). While initially cloned as a transcriptional regulator of the various steroidogenic enzyme genes in the adrenal and gonad, it has become clear through genetic ablation experiments in mice that SF-1 is an essential factor in adrenal and gonadal development and for the proper functioning of the hypothalamic-pituitary-gonadal axis. In addition, these studies have revealed that SF-1 is necessary for the formation of the ventromedial nucleus of the hypothalamus. While we have learned much since the initial cloning of SF-1, the mechanisms by which SF-1 regulates these various developmental programs remain elusive. This article focuses on the characterization of SF-1 and its emerging role in endocrine homeostasis. Specific attention is placed on the mechanisms of action of this unique member of the nuclear receptor superfamily.

  13. Computational Steroidogenesis Model To Predict Biochemical Responses to Endocrine Active Chemicals: Model Development and Cross Validation

    EPA Science Inventory

    Steroids, which have an important role in a wide range of physiological processes, are synthesized primarily in the gonads and adrenal glands through a series of enzyme-mediated reactions. The activity of steroidogenic enzymes can be altered by a variety of endocrine active chem...

  14. Integrative rodent models for assessing male reproductive toxicity of environmental endocrine active substances

    PubMed Central

    Auger, Jacques; Eustache, Florence; Rouiller-Fabre, Virginie; Canivenc-Lavier, Marie Chantal; Livera, Gabriel

    2014-01-01

    In the present review, we first summarize the main benefits, limitations and pitfalls of conventional in vivo approaches to assessing male reproductive structures and functions in rodents in cases of endocrine active substance (EAS) exposure from the postulate that they may provide data that can be extrapolated to humans. Then, we briefly present some integrated approaches in rodents we have recently developed at the organism level. We particularly focus on the possible effects and modes of action (MOA) of these substances at low doses and in mixtures, real-life conditions and at the organ level, deciphering the precise effects and MOA on the fetal testis. It can be considered that the in vivo experimental EAS exposure of rodents remains the first choice for studies and is a necessary tool (together with the epidemiological approach) for understanding the reproductive effects and MOA of EASs, provided the pitfalls and limitations of the rodent models are known and considered. We also provide some evidence that classical rodent models may be refined for studying the multiple consequences of EAS exposure, not only on the reproductive axis but also on various hormonally regulated organs and tissues, among which several are implicated in the complex process of mammalian reproduction. Such models constitute an interesting way of approaching human exposure conditions. Finally, we show that organotypic culture models are powerful complementary tools, especially when focusing on the MOA. All these approaches have contributed in a combinatorial manner to a better understanding of the impact of EAS exposure on human reproduction. PMID:24369134

  15. A Rat α-Fetoprotein Binding Activity Prediction Model to Facilitate Assessment of the Endocrine Disruption Potential of Environmental Chemicals.

    PubMed

    Hong, Huixiao; Shen, Jie; Ng, Hui Wen; Sakkiah, Sugunadevi; Ye, Hao; Ge, Weigong; Gong, Ping; Xiao, Wenming; Tong, Weida

    2016-04-01

    Endocrine disruptors such as polychlorinated biphenyls (PCBs), diethylstilbestrol (DES) and dichlorodiphenyltrichloroethane (DDT) are agents that interfere with the endocrine system and cause adverse health effects. Huge public health concern about endocrine disruptors has arisen. One of the mechanisms of endocrine disruption is through binding of endocrine disruptors with the hormone receptors in the target cells. Entrance of endocrine disruptors into target cells is the precondition of endocrine disruption. The binding capability of a chemical with proteins in the blood affects its entrance into the target cells and, thus, is very informative for the assessment of potential endocrine disruption of chemicals. α-fetoprotein is one of the major serum proteins that binds to a variety of chemicals such as estrogens. To better facilitate assessment of endocrine disruption of environmental chemicals, we developed a model for α-fetoprotein binding activity prediction using the novel pattern recognition method (Decision Forest) and the molecular descriptors calculated from two-dimensional structures by Mold² software. The predictive capability of the model has been evaluated through internal validation using 125 training chemicals (average balanced accuracy of 69%) and external validations using 22 chemicals (balanced accuracy of 71%). Prediction confidence analysis revealed the model performed much better at high prediction confidence. Our results indicate that the model is useful (when predictions are in high confidence) in endocrine disruption risk assessment of environmental chemicals though improvement by increasing number of training chemicals is needed. PMID:27023588

  16. A Rat α-Fetoprotein Binding Activity Prediction Model to Facilitate Assessment of the Endocrine Disruption Potential of Environmental Chemicals

    PubMed Central

    Hong, Huixiao; Shen, Jie; Ng, Hui Wen; Sakkiah, Sugunadevi; Ye, Hao; Ge, Weigong; Gong, Ping; Xiao, Wenming; Tong, Weida

    2016-01-01

    Endocrine disruptors such as polychlorinated biphenyls (PCBs), diethylstilbestrol (DES) and dichlorodiphenyltrichloroethane (DDT) are agents that interfere with the endocrine system and cause adverse health effects. Huge public health concern about endocrine disruptors has arisen. One of the mechanisms of endocrine disruption is through binding of endocrine disruptors with the hormone receptors in the target cells. Entrance of endocrine disruptors into target cells is the precondition of endocrine disruption. The binding capability of a chemical with proteins in the blood affects its entrance into the target cells and, thus, is very informative for the assessment of potential endocrine disruption of chemicals. α-fetoprotein is one of the major serum proteins that binds to a variety of chemicals such as estrogens. To better facilitate assessment of endocrine disruption of environmental chemicals, we developed a model for α-fetoprotein binding activity prediction using the novel pattern recognition method (Decision Forest) and the molecular descriptors calculated from two-dimensional structures by Mold2 software. The predictive capability of the model has been evaluated through internal validation using 125 training chemicals (average balanced accuracy of 69%) and external validations using 22 chemicals (balanced accuracy of 71%). Prediction confidence analysis revealed the model performed much better at high prediction confidence. Our results indicate that the model is useful (when predictions are in high confidence) in endocrine disruption risk assessment of environmental chemicals though improvement by increasing number of training chemicals is needed. PMID:27023588

  17. Exploring the Relationship of Autonomic and Endocrine Activity with Social Functioning in Adults with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Smeekens, I.; Didden, R.; Verhoeven, E. W. M.

    2015-01-01

    Several studies indicate that autonomic and endocrine activity may be related to social functioning in individuals with autism spectrum disorder (ASD), although the number of studies in adults is limited. The present study explored the relationship of autonomic and endocrine activity with social functioning in young adult males with ASD compared…

  18. Microsituations as an Active-Learning Tool To Teach Endocrine Pharmacology and Problem-Solving Skills.

    ERIC Educational Resources Information Center

    Brandt, Barbara F.; Lubawy, William C.

    1998-01-01

    Microsituations teaching is a case-based, active learning tool developed from cognitive learning theory to teach problem-solving skills to large classes while conserving faculty and other resources. Since implementing this method in an endocrine pharmacology course at the University of Kentucky, student performance on problem-solving examinations…

  19. In vitro metabolism and bioavailability tests for the predictive toxicology of endocrine active substances

    EPA Science Inventory

    Legislation and prospective legislative proposals internationally (may) require that chemicals are tested for their ability to disrupt the hormonal systems of animals. Chemicals found to test positive in vitro are considered to be endocrine active substances (EAS) and may be puta...

  20. Developing analytical approaches to explore the connectionbetween endocrine-active pharmaceuticals in waterto effects in fish

    EPA Science Inventory

    The emphasis of this research project was to develop, and optimize, a solid-phase extraction (SPE) method and high performance liquid chromatography-electrospray ionization- mass spectrometry (LC-MS/MS) method, such that a linkage between the detection of endocrine active pharma...

  1. The gut microbiome as a virtual endocrine organ with implications for farm and domestic animal endocrinology.

    PubMed

    O'Callaghan, T F; Ross, R P; Stanton, C; Clarke, G

    2016-07-01

    The gut microbiome exerts a marked influence on host physiology, and manipulation of its composition has repeatedly been shown to influence host metabolism and body composition. This virtual endocrine organ also has a role in the regulation of the plasma concentrations of tryptophan, an essential amino acid and precursor to serotonin, a key neurotransmitter within both the enteric and central nervous systems. Control over the hypothalamic-pituitary-adrenal axis also appears to be under the influence of the gut microbiota. This is clear from studies in microbiota-deficient germ-free animals with exaggerated responses to psychological stress that can be normalized by monocolonization with certain bacterial species including Bifidobacterium infantis. Therapeutic targeting of the gut microbiota may thus be useful in treating or preventing stress-related microbiome-gut-brain axis disorders and metabolic diseases, much the same way as redirections of metabolopathies can be achieved through more traditional endocrine hormone-based interventions. Moreover, the implications of these findings need to be considered in the context of farm and domestic animal physiology, behavior, and food safety. PMID:27345323

  2. Validation of noninvasive monitoring of adrenocortical endocrine activity in ground-feeding aardwolves (Proteles cristata): exemplifying the influence of consumption of inorganic material for fecal steroid analysis.

    PubMed

    Ganswindt, André; Muilwijk, Charlotte; Engelkes, Monique; Muenscher, Stefanie; Bertschinger, Henk; Paris, Monique; Palme, Rupert; Cameron, Elissa Z; Bennett, Nigel C; Dalerum, Fredrik

    2012-01-01

    Biologically inert material in feces may confound interpretations of noninvasive fecal endocrine data, because it may induce variance related to differences in foraging behavior rather than to differences in endocrine activity. We evaluated two different enzyme immunoassays (EIAs) for the noninvasive evaluation of adrenocortical activity in ground-feeding aardwolves (Proteles cristata) and tested the influence of soil content in aardwolf feces on the interpretation of fecal glucocorticoid metabolite data. Using adrenocorticotropic hormone (ACTH) challenges for validation, we successfully identified a cortisol EIA suitable for assessing adrenocortical activity in aardwolves. An alternatively tested 11-oxoetiocholanolone EIA failed to detect a biologically relevant signal after ACTH administration. Although the proportion of inorganic content in aardwolf feces did not alter qualitative conclusions from the endocrine data, the data related to mass of organic content had a larger amount of variance attributed to relevant biological contrasts and a lower amount of variance attributed to individual variation, compared with data related to total dry mass of extracted material. Compared with data expressed as dry mass of extracted material, data expressed as mass of organic content may provide a more refined and statistically powerful measure of endocrine activity in species that ingest large amounts of indigestible material. PMID:22418711

  3. Validation of noninvasive monitoring of adrenocortical endocrine activity in ground-feeding aardwolves (Proteles cristata): exemplifying the influence of consumption of inorganic material for fecal steroid analysis.

    PubMed

    Ganswindt, André; Muilwijk, Charlotte; Engelkes, Monique; Muenscher, Stefanie; Bertschinger, Henk; Paris, Monique; Palme, Rupert; Cameron, Elissa Z; Bennett, Nigel C; Dalerum, Fredrik

    2012-01-01

    Biologically inert material in feces may confound interpretations of noninvasive fecal endocrine data, because it may induce variance related to differences in foraging behavior rather than to differences in endocrine activity. We evaluated two different enzyme immunoassays (EIAs) for the noninvasive evaluation of adrenocortical activity in ground-feeding aardwolves (Proteles cristata) and tested the influence of soil content in aardwolf feces on the interpretation of fecal glucocorticoid metabolite data. Using adrenocorticotropic hormone (ACTH) challenges for validation, we successfully identified a cortisol EIA suitable for assessing adrenocortical activity in aardwolves. An alternatively tested 11-oxoetiocholanolone EIA failed to detect a biologically relevant signal after ACTH administration. Although the proportion of inorganic content in aardwolf feces did not alter qualitative conclusions from the endocrine data, the data related to mass of organic content had a larger amount of variance attributed to relevant biological contrasts and a lower amount of variance attributed to individual variation, compared with data related to total dry mass of extracted material. Compared with data expressed as dry mass of extracted material, data expressed as mass of organic content may provide a more refined and statistically powerful measure of endocrine activity in species that ingest large amounts of indigestible material.

  4. Current limitations and a path forward to improve testing for the environmental assessment of endocrine active substances

    EPA Science Inventory

    To assess the hazards and risks of possible endocrine active chemicals (EACs) there is a need for robust, validated test methods that detect perturbation of endocrine pathways of concern and provide insights reliable information as to assess to potential adverse effects on apical...

  5. Evaluation of potential endocrine activity of 2,4-dichlorophenoxyacetic acid using in vitro assays.

    PubMed

    Coady, Katherine K; Kan, H Lynn; Schisler, Melissa R; Gollapudi, B Bhaskar; Neal, Barbara; Williams, Amy; LeBaron, Matthew J

    2014-08-01

    The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) was evaluated in five in vitro screening assays to assess the potential for interaction with the androgen, estrogen and steroidogenesis pathways in the endocrine system. The assays were conducted to meet the requirements of the in vitro component of Tier 1 of the United States Environmental Protection Agency's Endocrine Disruptor Screening Program (EDSP), and included assays for estrogen receptor (ER) binding (rat uterine cytosol ER binding assay), ER-mediated transcriptional activation (HeLa-9903-ERα transactivation assay), androgen receptor (AR) binding (rat prostate cytosol AR binding assay), aromatase enzymatic activity inhibition (recombinant human CYP19 aromatase inhibition assay), and interference with steroidogenesis (H295R steroidogenesis assay). Results from these five assays demonstrated that 2,4-D does not have the potential to interact in vitro with the estrogen, androgen, or steroidogenesis pathways. These in vitro data are consistent with a corresponding lack of endocrine effects observed in apical in vivo animal studies, and thus provide important supporting data valuable in a comprehensive weight of evidence evaluation indicating a low potential of 2,4-D to interact with the endocrine system.

  6. Characterizing field sediments from three European river basins with special emphasis on endocrine effects - A recommendation for Potamopyrgus antipodarum as test organism.

    PubMed

    Schmitt, Claudia; Balaam, Jan; Leonards, Pim; Brix, Rikke; Streck, Georg; Tuikka, Anita; Bervoets, Lieven; Brack, Werner; van Hattum, Bert; Meire, Patrick; de Deckere, Eric

    2010-06-01

    The assessment of endocrine disrupting potentials of field sediments has until now been mostly limited to classical chemical analysis, in vitro assays and in vivo bioassays performed with vertebrates. There is an urgent need for easy, cheap and reproducible invertebrate tests which may be applied in certain monitoring activities. Since the mudsnail Potamopyrgus antipodarum is known to be tolerant to natural stressors, but also sensitive to endocrine disrupting chemicals, it is very likely that this organism could be suitable for the assessment of endocrine effects of e.g. field sediments. Within this study the endocrine potential of sediments in three European river basins was assessed. The yeast estrogen screen (YES) and a sediment contact test with P. antipodarum were performed. Furthermore, analyses of physico-chemical properties and concentrations of heavy metals, PAHs, organotins, natural steroids and alkylphenols were done. In the sediment contact test, the reproduction of the snail was promoted by a part of the sediments. This phenomenon could not be explained by their physico-chemical properties. However, at some of those sites a high estrogenic activity was detected in the YES, leading to the assumption that endocrine disrupting compounds could be responsible for those effects. This assumption could be confirmed to some extent with partially high concentrations of xeno-estrogens (e.g. nonylphenol) at the certain sites. Our study demonstrates the applicability of the test with P. antipodarum for a variety of sediments and once again points out the need of suitable in vivo biotests for the risk assessment of field sediments.

  7. The adipocyte as an endocrine organ in the regulation of metabolic homeostasis.

    PubMed

    Harwood, H James

    2012-07-01

    Over the past decade and a half it has become increasingly clear that adipose tissue is a much more complex organ than was initially considered and that its metabolic functions extend well beyond the classical actions of thermoregulation and of storage and release of fatty acids. In fact, it is now well established that adipose tissue plays a critical role in maintenance of energy homeostasis through secretion of a large number of adipokines that interact with central as well as peripheral organs such as the brain, liver, pancreas, and skeletal muscle to control diverse processes, such as food intake, energy expenditure, carbohydrate and lipid metabolism, blood pressure, blood coagulation, and inflammation. While many of these adipokines are adipocyte-derived and have a variety of endocrine functions, others are produced by resident macrophages and interact in a paracrine fashion to control adipocyte metabolism. It is also abundantly clear that the dysregulation of adipokine secretion and action that occurs in obesity plays a fundamental role in the development of a variety of cardiometabolic disorders, including the metabolic syndrome, type 2 diabetes, inflammatory disorders, and vascular disorders, that ultimately lead to coronary heart disease. Described herein are the traditional as well as endocrine roles of adipose tissue in controlling energy metabolism and their dysregulation in obesity that leads to development of cardiometabolic disorders, with a focus on what is currently known regarding the characteristics and roles in both health and disease of the adipocyte-derived adipokines, adiponectin, leptin, resistin, and retinol binding protein 4, and the resident macrophage-derived adipokines, tumor necrosis factor-α and interleukin-6. This article is part of a Special Issue entitled 'Central Control of Food Intake'.

  8. Endocrine-disrupting activity of chemicals in diesel exhaust and diesel exhaust particles.

    PubMed

    Takeda, Ken; Tsukue, Naomi; Yoshida, Seiichi

    2004-01-01

    Diesel exhaust (DE) is known as the main cause of air pollution. DE is a complex mixture of particulate and vapor-phase compounds. The soluble organic fraction of the particulate materials in DE contains thousands of compounds including a variety of polycyclic aromatic hydrocarbons and heavy metals. To clarify the endocrine-disrupting activities of DE, we have reviewed the reports about the effects of DE on the reproductive and brain-nervous systems, and the endocrine-disrupting action of diesel exhaust particles (DEP). In utero exposure to low levels (0.1 mg DEP/m3) of DE from day 2 postcoitum (p.c.) until day 13 p.c. reduced the expression level of Ad4BP/SF-1 mRNA and thereby might affect the development of gonads. Low levels of DE also reduced the expression of several genes known to play key roles in gonadal development, including an enzyme necessary for testosterone synthesis. Mature male rats exposed to DE during the fetal period showed an irreversible decrease in daily sperm production due to an insufficient number of Sertoli cells. DE exposure during the fetal period influenced the brain tissue in newborn mice. In the 3 mg DEP/m3 exposure group at 10 weeks of age, a significant reduction in performance was observed in the passive avoidance learning test in both male and female mice. In addition, the fetal exposure of mice to DE affected the emotional behaviors associated with the serotonergic and dopaminergic systems in the mouse brain. In toluidine blue-stained specimens from the DE-exposed group, edema around the vessels where fluorescent granular perithelial (FGP) cells exist and degenerated granules within the FGP cytoplasm were observed; similar findings were obtained by electron microscopic examination. DEP contain many substances that stimulate Ah receptors, such as the polycyclic aromatic hydrocarbon containing benzo[a]pyrene. DEP also contain substances with estrogenic, antiestrogenic and antiandrogenic activities. The neutral substance fraction of

  9. Monitoring endocrine disrupting compounds and estrogenic activity in tap water from Central Spain.

    PubMed

    Esteban, S; Gorga, M; González-Alonso, S; Petrovic, M; Barceló, D; Valcárcel, Y

    2014-01-01

    The aims of this study are to investigate the presence of 30 substances known or thought to act as endocrine disrupting compounds in tap water from the main water supply areas for region of Madrid, to determine the total estrogenic activity of the samples analysed and to estimate the health risk for the population resulting from those compounds found at detectable concentrations. To this end, a one-off composite sampling was performed in August 2012 in which six tap water samples were collected from private residences in the drinking water supply network of the region of Madrid. A total of 14 of the 30 endocrine disruptors analysed were found at concentrations ranging from 0.3 to 165 ng/L. The organophosphorus flame retardants were detected at the highest concentrations followed by the plasticizer bisphenol A, alkylphenols, anticorrosion agents and preservatives. Tap water in the region of Madrid is contaminated with traces (ng/L) of compounds with endocrine disrupting properties. Although the concentrations of endocrine disrupting compounds obtained are too low to be able to confirm a public health risk, and no risk has been detected upon evaluation, it should be remembered that these compounds act at very low doses and that their effects may only appear in the long term. PMID:24728544

  10. An assessment of endocrine activity in Australian rivers using chemical and in vitro analyses.

    PubMed

    Scott, Philip D; Bartkow, Michael; Blockwell, Stephen J; Coleman, Heather M; Khan, Stuart J; Lim, Richard; McDonald, James A; Nice, Helen; Nugegoda, Dayanthi; Pettigrove, Vincent; Tremblay, Louis A; Warne, Michael St J; Leusch, Frederic D L

    2014-11-01

    Studies on endocrine disruption in Australia have mainly focused on wastewater effluents. Limited knowledge exists regarding the relative contribution of different potential sources of endocrine active compounds (EACs) to the aquatic environment (e.g., pesticide run-off, animal farming operations, urban stormwater, industrial inputs). In this study, 73 river sites across mainland Australia were sampled quarterly for 1 year. Concentrations of 14 known EACs including natural and synthetic hormones and industrial compounds were quantified by chemical analysis. EACs were detected in 88 % of samples (250 of 285) with limits of quantification (LOQ) ranging from 0.05 to 20 ng/l. Bisphenol A (BPA; LOQ = 20 ng/l) was the most frequently detected EAC (66 %) and its predicted no-effect concentration (PNEC) was exceeded 24 times. The most common hormone was estrone, detected in 28 % of samples (LOQ = 1 ng/l), and the PNEC was also exceeded 24 times. 17α-Ethinylestradiol (LOQ = 0.05 ng/l) was detected in 10 % of samples at concentrations ranging from 0.05 to 0.17 ng/l. It was detected in many samples with no wastewater influence, and the PNEC was exceeded 13 times. In parallel to the chemical analysis, endocrine activity was assessed using a battery of CALUX bioassays. Estrogenic activity was detected in 19 % (53 of 285) of samples (LOQ = 0.1 ng/l 17β-estradiol equivalent; EEQ). Seven samples exhibited estrogenic activity (1-6.5 ng/l EEQ) greater than the PNEC for 17β-estradiol. Anti-progestagenic activity was detected in 16 % of samples (LOQ = 8 ng/l mifepristone equivalents; MifEQ), but the causative compounds are unknown. With several compounds and endocrine activity exceeding PNEC values, there is potential risk to the Australian freshwater ecosystems.

  11. Multi-tiered Approach to Development of Increased Throughput Assay Models to Assess Endocrine-Disrupting Activity of Chemicals

    EPA Science Inventory

    Screening for endocrine-disrupting chemicals (EDCs) requires sensitive, scalable assays. Current high-throughput screening (HTPS) approaches for estrogenic and androgenic activity yield rapid results, but many are not sensitive to physiological hormone concentrations, suggesting ...

  12. Proinflammatory Cytokines Induce Endocrine Differentiation in Pancreatic Ductal Cells via STAT3-Dependent NGN3 Activation.

    PubMed

    Valdez, Ivan Achel; Dirice, Ercument; Gupta, Manoj K; Shirakawa, Jun; Teo, Adrian Kee Keong; Kulkarni, Rohit N

    2016-04-19

    A major goal of diabetes research is to develop strategies that replenish pancreatic insulin-producing beta cells. One emerging strategy is to harness pancreatic plasticity-the ability of pancreatic cells to undergo cellular interconversions-a phenomenon implicated in physiological stress and pancreatic injury. Here, we investigate the effects of inflammatory cytokine stress on the differentiation potential of ductal cells in a human cell line, in mouse ductal cells by pancreatic intraductal injection, and during the progression of autoimmune diabetes in the non-obese diabetic (NOD) mouse model. We find that inflammatory cytokine insults stimulate epithelial-to-mesenchymal transition (EMT) as well as the endocrine program in human pancreatic ductal cells via STAT3-dependent NGN3 activation. Furthermore, we show that inflammatory cytokines activate ductal-to-endocrine cell reprogramming in vivo independent of hyperglycemic stress. Together, our findings provide evidence that inflammatory cytokines direct ductal-to-endocrine cell differentiation, with implications for beta cell regeneration. PMID:27068459

  13. Endocrine-Disrupting Activity of Hydraulic Fracturing Chemicals and Adverse Health Outcomes After Prenatal Exposure in Male Mice.

    PubMed

    Kassotis, Christopher D; Klemp, Kara C; Vu, Danh C; Lin, Chung-Ho; Meng, Chun-Xia; Besch-Williford, Cynthia L; Pinatti, Lisa; Zoeller, R Thomas; Drobnis, Erma Z; Balise, Victoria D; Isiguzo, Chiamaka J; Williams, Michelle A; Tillitt, Donald E; Nagel, Susan C

    2015-12-01

    Oil and natural gas operations have been shown to contaminate surface and ground water with endocrine-disrupting chemicals. In the current study, we fill several gaps in our understanding of the potential environmental impacts related to this process. We measured the endocrine-disrupting activities of 24 chemicals used and/or produced by oil and gas operations for five nuclear receptors using a reporter gene assay in human endometrial cancer cells. We also quantified the concentration of 16 of these chemicals in oil and gas wastewater samples. Finally, we assessed reproductive and developmental outcomes in male C57BL/6J mice after the prenatal exposure to a mixture of these chemicals. We found that 23 commonly used oil and natural gas operation chemicals can activate or inhibit the estrogen, androgen, glucocorticoid, progesterone, and/or thyroid receptors, and mixtures of these chemicals can behave synergistically, additively, or antagonistically in vitro. Prenatal exposure to a mixture of 23 oil and gas operation chemicals at 3, 30, and 300 μg/kg · d caused decreased sperm counts and increased testes, body, heart, and thymus weights and increased serum testosterone in male mice, suggesting multiple organ system impacts. Our results suggest possible adverse developmental and reproductive health outcomes in humans and animals exposed to potential environmentally relevant levels of oil and gas operation chemicals.

  14. Endocrine-Disrupting Activity of Hydraulic Fracturing Chemicals and Adverse Health Outcomes After Prenatal Exposure in Male Mice.

    PubMed

    Kassotis, Christopher D; Klemp, Kara C; Vu, Danh C; Lin, Chung-Ho; Meng, Chun-Xia; Besch-Williford, Cynthia L; Pinatti, Lisa; Zoeller, R Thomas; Drobnis, Erma Z; Balise, Victoria D; Isiguzo, Chiamaka J; Williams, Michelle A; Tillitt, Donald E; Nagel, Susan C

    2015-12-01

    Oil and natural gas operations have been shown to contaminate surface and ground water with endocrine-disrupting chemicals. In the current study, we fill several gaps in our understanding of the potential environmental impacts related to this process. We measured the endocrine-disrupting activities of 24 chemicals used and/or produced by oil and gas operations for five nuclear receptors using a reporter gene assay in human endometrial cancer cells. We also quantified the concentration of 16 of these chemicals in oil and gas wastewater samples. Finally, we assessed reproductive and developmental outcomes in male C57BL/6J mice after the prenatal exposure to a mixture of these chemicals. We found that 23 commonly used oil and natural gas operation chemicals can activate or inhibit the estrogen, androgen, glucocorticoid, progesterone, and/or thyroid receptors, and mixtures of these chemicals can behave synergistically, additively, or antagonistically in vitro. Prenatal exposure to a mixture of 23 oil and gas operation chemicals at 3, 30, and 300 μg/kg · d caused decreased sperm counts and increased testes, body, heart, and thymus weights and increased serum testosterone in male mice, suggesting multiple organ system impacts. Our results suggest possible adverse developmental and reproductive health outcomes in humans and animals exposed to potential environmentally relevant levels of oil and gas operation chemicals. PMID:26465197

  15. Endocrine-disrupting activity of hydraulic fracturing chemicals and adverse health outcomes after prenatal exposure in male mice

    USGS Publications Warehouse

    Kassotis, Christopher D.; Klemp, Kara C.; Vu, Danh C.; Lin, Chung-Ho; Meng, Chun-Xia; Besch-Williford, Cynthia L.; Pinatti, Lisa; Zoeller, R. Thomas; Drobnis, Erma Z.; Balise, Victoria D.; Isiguzo, Chiamaka J.; Williams, Michelle A.; Tillitt, Donald E.; Nagel, Susan C.

    2015-01-01

    Oil and natural gas operations have been shown to contaminate surface and ground water with endocrine-disrupting chemicals. In the current study, we fill several gaps in our understanding of the potential environmental impacts related to this process. We measured the endocrine-disrupting activities of 24 chemicals used and/or produced by oil and gas operations for five nuclear receptors using a reporter gene assay in human endometrial cancer cells. We also quantified the concentration of 16 of these chemicals in oil and gas wastewater samples. Finally, we assessed reproductive and developmental outcomes in male C57BL/6J mice after the prenatal exposure to a mixture of these chemicals. We found that 23 commonly used oil and natural gas operation chemicals can activate or inhibit the estrogen, androgen, glucocorticoid, progesterone, and/or thyroid receptors, and mixtures of these chemicals can behave synergistically, additively, or antagonistically in vitro. Prenatal exposure to a mixture of 23 oil and gas operation chemicals at 3, 30, and 300 μg/kg · d caused decreased sperm counts and increased testes, body, heart, and thymus weights and increased serum testosterone in male mice, suggesting multiple organ system impacts. Our results suggest possible adverse developmental and reproductive health outcomes in humans and animals exposed to potential environmentally relevant levels of oil and gas operation chemicals.

  16. Analysis and occurrence of endocrine-disrupting compounds and estrogenic activity in the surface waters of Central Spain.

    PubMed

    Esteban, S; Gorga, M; Petrovic, M; González-Alonso, S; Barceló, D; Valcárcel, Y

    2014-01-01

    Endocrine-disrupting compounds (EDCs) are chemical compounds with the ability to alter the hormonal systems of organisms. Such compounds are used in several industrial and domestic activities and reach the aquatic environment via wastewater discharge. The aim of this study is to assess the occurrence of 30 EDCs and related compounds in the surface waters of central Spain and to determine the overall estrogenic activity of environmental samples. This study analyzed a large number of EDCs and other emergent or suspected compounds with endocrine-disrupting activity. The results have shown the presence of 19 EDCs at concentrations ranging from 2 to 5928 ng L(-1). Organophosphorus-based flame retardants, alkylphenolic compounds and anticorrosives were found at the highest concentrations. Furthermore, although insufficient data are available to calculate an average over time, these preliminary results show the need to monitor the waters in both rivers studied. Alkylphenolic compounds, particularly nonylphenol, were the main contributors to overall estrogenicity. A higher concentration of the compounds studied was detected in the river Jarama, although the estrogenicity expressed as estradiol equivalents (EEQs) was higher in the river Manzanares due to a higher concentration of nonylphenol. However, the total estrogenicity did not exceed 1 ng L(-1) (EEQ), which is the level that may cause estrogenic effects in aquatic organisms, in any of the samples. In conclusion, the potential estrogenic risk in both rivers is low, although organophosphorus-based flame retardants may increase this risk as they were found at high levels in all samples. Unfortunately, these compounds could not be taken into account when calculating the estrogenic activity due to the lack of activity data for them. For future investigations, it will be important to assess the estrogenicity provided by these flame retardants. Due to the significant concentrations of EDCs detected in both rivers, further

  17. Skeletal muscle as an endocrine organ: Role of [Na+]i/[K+]i-mediated excitation-transcription coupling

    PubMed Central

    Kapilevich, Leonid V.; Kironenko, Tatyana A.; Zaharova, Anna N.; Kotelevtsev, Yuri V.; Dulin, Nickolai O.; Orlov, Sergei N.

    2016-01-01

    Summary During the last two decades numerous research teams demonstrated that skeletal muscles function as an exercise-dependent endocrine organ secreting dozens of myokines. Variety of physiological and pathophysiological implications of skeletal muscle myokines secretion has been described; however, upstream signals and sensing mechanisms underlying this phenomenon remain poorly understood. It is well documented that in skeletal muscles intensive exercise triggers dissipation of transmembrane gradient of monovalent cations caused by permanent activation of voltage-gated Na+ and K+ channels. Recently, we demonstrated that sustained elevation of the [Na+]i/[K+]i ratio triggers expression of dozens ubiquitous genes including several canonical myokines, such as interleukin 6 and cyclooxygenase 2, in the presence of intra- and extracellular Ca2+ chelators. These data allowed us to suggest a novel [Na+]i/[K+]i-sensitive, Ca2+i-independent mechanism of excitation-transcription coupling which triggers myokine production. This pathway exists in parallel with canonical signaling mediated by Ca2+i, AMP-activated protein kinase and hypoxia-inducible factor 1α (HIF-1α). In our mini-review we briefly summarize data supporting this hypothesis as well as unresolved issues aiming to forthcoming studies. PMID:27610402

  18. Sorption and toxicity reduction of pharmaceutically active compounds and endocrine disrupting chemicals in the presence of colloidal humic acid.

    PubMed

    Kim, Injeong; Kim, Hyo-Dong; Jeong, Tae-Yong; Kim, Sang Don

    2016-01-01

    This study investigated the toxicity changes and sorption of pharmaceuticals and endocrine disrupters in the presence of humic acid (HA). For the sorption experiment, a dead end filtration (DEF) system was used to separate bound and free-form target compounds. An algae growth inhibition test and E-screen assay were conducted to estimate the toxic effect of pharmaceutically active compounds (PhACs) and endocrine disrupting chemicals (EDCs), respectively. The permeate concentration was confirmed using liquid chromatography-mass spectrometry. In the sorption test, we observed significant sorption of PhACs and EDCs on colloidal HA, except for sulfamethoxazole (SMX). The values of log KCOC derived from DEF determinations ranged from 4.40 to 5.03. The removal efficiency varied with the HA concentration and the target chemical properties. Tetracycline and 4-octylphenol showed the highest sorption or removal efficiency (≈50%), even at 5 mg C/L HA. The algal growth inhibition of PhACs and the estrogenic effects of EDCs were significantly decreased in proportion to HA concentrations, except for SMX. In addition, the chemical analysis results showed a positive relationship with the bioassay results. Consequently, the sorption of PhACs and EDCs onto colloidal HA should be emphasized in natural environments because it significantly reduces bioavailable concentrations and toxicity to aquatic organisms. PMID:27533865

  19. Potential endocrine disrupting organic chemicals in treated municipal wastewater and river water

    USGS Publications Warehouse

    Barber, L.B.; Brown, G.K.; Zaugg, S.D.

    2000-01-01

    Select endocrine disrupting organic chemicals were measured in treated wastewater from Chicago, IL, Minneapolis/St. Paul, MN, Detroit, MI, and Milwaukee, WI, and in the Des Plaines, Illinois, and Minnesota Rivers during the fall of 1997 and the spring of 1998. Emphasis was given to alkylphenolpolyethoxylate (APEO) derived compounds, although 17-??-estradiol, bisphenol A, caffeine, total organic carbon, ethylenediaminetetraacetic acid (EDTA), and other compounds also were measured. Contaminants were isolated by continuous liquid-liquid extraction (CLLE) with methylene chloride and analyzed by gas chromatography/mass spectrometry in full scan and selected ion monitoring modes. The extracts were derivatized to form the methyl esters of alkylphenolethoxycarboxylates (APEC), and EDTA was isolated by evaporation and derivatized to form the tetrapropyl ester. The mass spectra of nonylphenol (NP) and octylphenol (OP) compounds are complex and show variations among the different ethoxylate and carboxylate homologs, reflecting variations in the ethylene oxide chain length. Recoveries for target compounds and surrogate standards ranged from 20-130%, with relative standard deviations of 9.9-53%. Detection limits for the various compounds ranged from 0.06-0.35 ??g/L. Analysis of the wastewater effluents detected a number of compounds including NP, NPEO, OP, OPEO, NPEC, caffeine, and EDTA at concentrations ranging from <1-439 ??g/L, with EDTA and NPEC being most abundant. There was variability in compound distributions and concentrations between the various sewage treatment plants, indicating differences in treatment type and influent composition. Several wastewater-derived compounds were detected in the river samples, with EDTA and NPEC persisting for considerable distance downstream from wastewater discharges, and NP and NPEO being attenuated more rapidly.

  20. Classical Nuclear Hormone Receptor Activity as a Mediator of Complex Concentration Response Relationships for Endocrine Active Compounds

    PubMed Central

    Cookman, Clifford J.; Belcher, Scott M.

    2014-01-01

    Nonmonotonic concentration response relationships are frequently observed for endocrine active ligands that act via nuclear receptors. The curve of best fit for nonmonotonic concentration response relationships are often inverted U-shaped with effects at intermediate concentrations that are different from effects at higher or lower concentrations. Cytotoxicity is a major mode of action responsible for inverted U-shaped concentration response relationships. However, evidence suggests that ligand selectivity, activation of multiple molecular targets, concerted regulation of multiple opposing endpoints, and multiple ligand binding sites within nuclear receptors also contribute to nonmonotonic concentration response relationships of endocrine active ligands. This review reports the current understanding of mechanisms involved in classical nuclear receptor mediated nonmonotonic concentration response relationships with a focus on studies published between 2012 and 2014. PMID:25299165

  1. Endocrine glands

    MedlinePlus

    Endocrine glands release (secrete) hormones into the bloodstream. The endocrine glands include: Adrenal Hypothalamus Islets of Langerhans in the pancreas Ovaries Parathyroid Pineal Pituitary Testes Thyroid

  2. QSAR classification models for the screening of the endocrine-disrupting activity of perfluorinated compounds.

    PubMed

    Kovarich, S; Papa, E; Li, J; Gramatica, P

    2012-01-01

    Perfluorinated compounds (PFCs) are a class of emerging pollutants still widely used in different materials as non-adhesives, waterproof fabrics, fire-fighting foams, etc. Their toxic effects include potential for endocrine-disrupting activity, but the amount of experimental data available for these pollutants is limited. The use of predictive strategies such as quantitative structure-activity relationships (QSARs) is recommended under the REACH regulation, to fill data gaps and to screen and prioritize chemicals for further experimentation, with a consequent reduction of costs and number of tested animals. In this study, local classification models for PFCs were developed to predict their T4-TTR (thyroxin-transthyretin) competing potency. The best models were selected by maximizing the sensitivity and external predictive ability. These models, characterized by robustness, good predictive power and a defined applicability domain, were applied to predict the activity of 33 other PFCs of environmental concern. Finally, classification models recently published by our research group for T4-TTR binding of brominated flame retardants and for estrogenic and anti-androgenic activity were applied to the studied perfluorinated chemicals to compare results and to further evaluate the potential for these PFCs to cause endocrine disruption.

  3. The effects of nanomaterials as endocrine disruptors.

    PubMed

    Iavicoli, Ivo; Fontana, Luca; Leso, Veruscka; Bergamaschi, Antonio

    2013-08-14

    In recent years, nanoparticles have been increasingly used in several industrial, consumer and medical applications because of their unique physico-chemical properties. However, in vitro and in vivo studies have demonstrated that these properties are also closely associated with detrimental health effects. There is a serious lack of information on the potential nanoparticle hazard to human health, particularly on their possible toxic effects on the endocrine system. This topic is of primary importance since the disruption of endocrine functions is associated with severe adverse effects on human health. Consequently, in order to gather information on the hazardous effects of nanoparticles on endocrine organs, we reviewed the data available in the literature regarding the endocrine effects of in vitro and in vivo exposure to different types of nanoparticles. Our aim was to understand the potential endocrine disrupting risks posed by nanoparticles, to assess their underlying mechanisms of action and identify areas in which further investigation is needed in order to obtain a deeper understanding of the role of nanoparticles as endocrine disruptors. Current data support the notion that different types of nanoparticles are capable of altering the normal and physiological activity of the endocrine system. However, a critical evaluation of these findings suggests the need to interpret these results with caution since information on potential endocrine interactions and the toxicity of nanoparticles is quite limited.

  4. The Effects of Nanomaterials as Endocrine Disruptors

    PubMed Central

    Iavicoli, Ivo; Fontana, Luca; Leso, Veruscka; Bergamaschi, Antonio

    2013-01-01

    In recent years, nanoparticles have been increasingly used in several industrial, consumer and medical applications because of their unique physico-chemical properties. However, in vitro and in vivo studies have demonstrated that these properties are also closely associated with detrimental health effects. There is a serious lack of information on the potential nanoparticle hazard to human health, particularly on their possible toxic effects on the endocrine system. This topic is of primary importance since the disruption of endocrine functions is associated with severe adverse effects on human health. Consequently, in order to gather information on the hazardous effects of nanoparticles on endocrine organs, we reviewed the data available in the literature regarding the endocrine effects of in vitro and in vivo exposure to different types of nanoparticles. Our aim was to understand the potential endocrine disrupting risks posed by nanoparticles, to assess their underlying mechanisms of action and identify areas in which further investigation is needed in order to obtain a deeper understanding of the role of nanoparticles as endocrine disruptors. Current data support the notion that different types of nanoparticles are capable of altering the normal and physiological activity of the endocrine system. However, a critical evaluation of these findings suggests the need to interpret these results with caution since information on potential endocrine interactions and the toxicity of nanoparticles is quite limited. PMID:23949635

  5. The effects of nanomaterials as endocrine disruptors.

    PubMed

    Iavicoli, Ivo; Fontana, Luca; Leso, Veruscka; Bergamaschi, Antonio

    2013-01-01

    In recent years, nanoparticles have been increasingly used in several industrial, consumer and medical applications because of their unique physico-chemical properties. However, in vitro and in vivo studies have demonstrated that these properties are also closely associated with detrimental health effects. There is a serious lack of information on the potential nanoparticle hazard to human health, particularly on their possible toxic effects on the endocrine system. This topic is of primary importance since the disruption of endocrine functions is associated with severe adverse effects on human health. Consequently, in order to gather information on the hazardous effects of nanoparticles on endocrine organs, we reviewed the data available in the literature regarding the endocrine effects of in vitro and in vivo exposure to different types of nanoparticles. Our aim was to understand the potential endocrine disrupting risks posed by nanoparticles, to assess their underlying mechanisms of action and identify areas in which further investigation is needed in order to obtain a deeper understanding of the role of nanoparticles as endocrine disruptors. Current data support the notion that different types of nanoparticles are capable of altering the normal and physiological activity of the endocrine system. However, a critical evaluation of these findings suggests the need to interpret these results with caution since information on potential endocrine interactions and the toxicity of nanoparticles is quite limited. PMID:23949635

  6. Endocrine activity of alternatives to BPA found in thermal paper in Switzerland.

    PubMed

    Goldinger, Daniela M; Demierre, Anne-Laure; Zoller, Otmar; Rupp, Heinz; Reinhard, Hans; Magnin, Roxane; Becker, Thomas W; Bourqui-Pittet, Martine

    2015-04-01

    Alternatives to bisphenol A (BPA) are more and more used in thermal paper receipts. To get an overview of the situation in Switzerland, 124 thermal paper receipts were collected and analyzed. Whereas BPA was detected in most samples (n=100), some alternatives, namely bisphenol S (BPS), Pergafast® 201 and D-8 have been found in 4, 11 and 9 samples respectively. As no or few data on their endocrine activity are available, these chemicals and bisphenol F (BPF) were tested in vitro using the H295R steroidogenesis assay. 17β-Estradiol production was induced by BPA and BPF, whereas free testosterone production was inhibited by BPA and BPS. Both non-bisphenol substances did not show significant effects. The binding affinity to 16 proteins and the toxicological potential (TP) were further calculated in silico using VirtualToxLab™. TP values lay between 0.269 and 0.476 and the main target was the estrogen receptor β (84.4 nM to 1.33 μM). A substitution of BPA by BPF and BPS should be thus considered with caution, since they exhibit almost a similar endocrine activity as BPA. D-8 and Pergafast® 201 could be alternatives to replace BPA, however further analyses are needed to better characterize their effects on the hormonal system.

  7. Endocrine system: part 1.

    PubMed

    Johnstone, Carolyn; Hendry, Charles; Farley, Alistair; McLafferty, Ella

    2014-05-27

    This article, which forms part of the life sciences series and is the first of two articles on the endocrine system, examines the structure and function of the organs of the endocrine system. It is important that nurses understand how the endocrine system works and its role in maintaining health. The role of the endocrine system and the types, actions and control of hormones are explored. The gross structure of the pituitary and thyroid glands are described along with relevant physiology. Several disorders of the thyroid gland are outlined. The second article examines growth hormone, the pancreas and adrenal glands.

  8. Ex situ bioengineering of bioartificial endocrine glands: a new frontier in regenerative medicine of soft tissue organs.

    PubMed

    Toni, Roberto; Tampieri, Anna; Zini, Nicoletta; Strusi, Valentina; Sandri, Monica; Dallatana, Davide; Spaletta, Giulia; Bassoli, Elena; Gatto, Andrea; Ferrari, Andrea; Martin, Ivan

    2011-10-20

    Ex situ bioengineering is one of the most promising perspectives in the field of regenerative medicine allowing for organ reconstruction outside the living body; i.e. on the laboratory bench. A number of hollow viscera of the cardiovascular, respiratory, genitourinary, and digestive systems have been successfully bioengineered ex situ, exploiting biocompatible scaffolds with a 3D morphology that recapitulates that of the native organ (organomorphic scaffold). In contrast, bioengineering of entire soft tissue organs and, in particular endocrine glands still remains a substantial challenge. Primary reasons are that no organomorphic scaffolding for endocrine viscera have as yet been entirely assembled using biocompatible materials, nor is there a bioreactor performance capable of supporting growth within the thickness range of the regenerating cell mass which has proven to be reliable enough to ensure formation of a complete macroscopic gland ex situ. Current technical options for reconstruction of endocrine viscera include either biocompatible 3D reticular scaffolds lacking any organomorphic geometry, or allogenic/xenogenic acellular 3D matrices derived from a gland similar to that to be bioengineered, eventually recellularized by autologous/heterologous cells. In 2007, our group designed, using biocompatible material, an organomorphic scaffold-bioreactor unit for bioengineering ex situ the human thyroid gland, chosen as a model for its simple anatomical organization (repetitive follicular cavities). This unit reproduces both the 3D native geometry of the human thyroid stromal/vascular scaffold, and the natural thyrocyte/vascular interface. It is now under intense investigation as an experimental tool to test cellular 3D auto-assembly of thyroid tissue and its related vascular system up to the ex situ generation of a 3D macroscopic thyroid gland. We believe that these studies will lay the groundwork for a new concept in regenerative medicine of soft tissue and

  9. Proteomic Analysis of the Reproductive Organs of the Hermaphroditic Gastropod Lymnaea stagnalis Exposed to Different Endocrine Disrupting Chemicals

    PubMed Central

    Giusti, Arnaud; Leprince, Pierre; Mazzucchelli, Gabriel; Thomé, Jean-Pierre; Lagadic, Laurent; Ducrot, Virginie; Joaquim-Justo, Célia

    2013-01-01

    Many studies have reported perturbations of mollusc reproduction following exposure to low concentrations (ng/L range) of endocrine disrupting chemicals (EDCs). However, the mechanisms of action of these molecules on molluscs are still poorly understood. Investigation of the modifications of protein expression in organisms exposed to chemicals using proteomic methods can provide a broader and more comprehensive understanding of adverse impacts of pollution on organisms than conventional biochemical biomarkers (e.g., heat-shock proteins, metallothioneins, GST, EROD). In this study we have investigated the impacts of four chemicals, which exhibit different endocrine disrupting properties in vertebrates, on the proteome of the hermaphroditic freshwater pulmonate gastropod Lymnaea stagnalis after 21 days of exposure. Testosterone, tributyltin, chlordecone and cyproterone acetate were chosen as tested compounds as they can induce adverse effects on the reproduction of this snail. The 2D-DIGE method was used to identify proteins whose expression was affected by these compounds. In addition to modifying the expression of proteins involved in the structure and function of the cytoskeleton, chemicals had impacts on the expression of proteins involved in the reproduction of L. stagnalis. Exposure to 19.2 µg/L of chlordecone increased the abundance of ovipostatin, a peptide transmitted during mating through seminal fluid, which reduces oviposition in this species. The expression of yolk ferritin, the vitellogenin equivalent in L. stagnalis, was reduced after exposure to 94.2 ng Sn/L of tributyltin. The identification of yolk ferritin and the modification of its expression in snails exposed to chemicals were refined using western blot analysis. Our results showed that the tested compounds influenced the abundance of yolk ferritin in the reproductive organs. Alteration in proteins involved in reproductive pathways (e.g., ovipostatin and yolk ferritin) could constitute relevant

  10. Before the curtain falls: endocrine-active pesticides--a German contamination legacy.

    PubMed

    Schulte-Oehlmann, Ulrike; Oehlmann, Jörg; Keil, Florian

    2011-01-01

    The European Parliament recently approved a new EU regulation aimed at eliminating the use of pesticides that have unwanted endocrine-disrupting properties. The test criteria for these chemicals are slated to be finalized by 2013. For this reason, in this review, we have evaluated the meta data of lists and databanks that address pesticides with potentially endocrine-disrupting properties, and have checked which of the 250 active ingredients currently in use in Germany are affected. Azoles, dithio-carbamates/carbamates, and pyrethroids were most frequently rated as endocrine-active ingredients. In Germany, assessments have shown that total environmental pesticide emission is equivalent to approximately 0.1% of total pesticide use.Courtyard drainage and field runoff are regarded to constitute the most important sources of pesticide emission into the aquatic environment. In addition, in several investigations of drinking- and groundwater contamination, various pesticide-active ingredients and their metabolites were confirmed to be contaminants. Water suppliers recorded the following pesticides or their metabolites as being most frequently detected in drinking water: atrazine, desethylatrazine, diuron, simazine, isoproturon,and its dichlobenil metabolite 2,6-dichlorobenzamide. Surface water contamination results mainly from substances that are no longer approved by EU pesticide regulation. The most frequently detected pesticides in streaming waters that are still authorized were bentazone, diuron, glyphosate, isoproturon, MCPA, mecoprop,metamitron, pendimethalin, and tebuconazole. Pesticide residues in comestible goods of herbal origin are periodically detected in all EU member countries. The European Commission recently published results showing that 54% of all monitoring samples were devoid of positive findings. Of samples showing detectable residues, 42% were below, and 4.4% exceeded the EUMRLs. Monitoring data over a 10-year period revealed that the percentage of

  11. Mammalian development in a changing environment: exposure to endocrine disruptors reveals the developmental plasticity of steroid-hormone target organs.

    PubMed

    Markey, Caroline M; Coombs, Macall A; Sonnenschein, Carlos; Soto, Ana M

    2003-01-01

    Recent findings in the field of environmental endocrine disruption have revealed that developmental exposure to estrogenic chemicals induces morphological, functional, and behavioral anomalies associated with reproduction. The aim of the present study was to determine the effects of in utero exposure to low doses of the estrogenic chemical bisphenol A (BPA) on the development of the female reproductive tissues and mammary glands in CD-1 mice. Humans are exposed to BPA, which leaches from dental materials and plastic food and beverage containers. Here we report that prenatal exposure to BPA induces alterations in tissue organization within the ovaries and mammary glands and disrupts estrous cyclicity in adulthood. Because estrogen receptors are expressed developmentally in these estrogen-target organs, we propose that BPA may directly affect the expression of genes involved in their morphogenesis. In addition, alterations in the sexual differentiation of the brain, and thus the hypothalamic-pituitary-gonadal axis, may further contribute to the observed phenotype. The emerging field of endocrine disruptors promises to provide new insights into the mechanisms underlying the development of hormone-target organs and demonstrates that the environment plays important roles in the making of phenotypes.

  12. [Environmental contaminants and endocrine disruptors].

    PubMed

    Fontenele, Eveline Gadelha Pereira; Martins, Manoel Ricardo Alves; Quidute, Ana Rosa Pinto; Montenegro, Renan Magalhães

    2010-02-01

    The toxicity of various pollutants has been routinely investigated according to their teratogenic and carcinogenic effects. In the last few decades, however, many of such pollutants have been shown to adversely affect the endocrine system of human beings and other species. Currently, more than eleven million chemical substances are known in the world, and approximately 3,000 are produced on a large scale. Numerous chemical composites of domestic, industrial and agricultural use have been shown to influence hormonal activity. Examples of such chemical products with estrogenic activity are substances used in cosmetics, anabolizing substances for animal feeding, phytoestrogens and persistent organic pollutants (POPs). These agents are seen in residential, industrial and urban sewerage system effluents and represent an important source of environmental contamination. The International Programme on Chemical Safety (IPCS) defines as endocrine disruptors substances or mixtures seen in the environment capable of interfering with endocrine system functions resulting in adverse effects in an intact organism or its offspring. In this article the authors present a current literature review about the role of these pollutants in endocrine and metabolic diseases, probable mechanisms of action, and suggest paths of investigation and possible strategies for prevention and reduction of its possible damages. PMID:20414542

  13. Ecological risk assessment of endocrine disruptors.

    PubMed Central

    Hutchinson, T H; Brown, R; Brugger, K E; Campbell, P M; Holt, M; Länge, R; McCahon, P; Tattersfield, L J; van Egmond, R

    2000-01-01

    The European Centre for Ecotoxicology and Toxicology of Chemicals proposes a tiered approach for the ecological risk assessment of endocrine disruptors, integrating exposure and hazard (effects) characterization. Exposure assessment for endocrine disruptors should direct specific tests for wildlife species, placing hazard data into a risk assessment context. Supplementing the suite of mammalian screens now under Organization for Economic Cooperation and Development (OECD) validation, high priority should be given to developing a fish screening assay for detecting endocrine activity in oviparous species. Taking into account both exposure characterization and alerts from endocrine screening, higher tier tests are also a priority for defining adverse effects. We propose that in vivo mammalian and fish assays provide a comprehensive screening battery for diverse hormonal functions (including androgen, estrogen, and thyroid hormone), whereas Amphibia should be considered at higher tiers if there are exposure concerns. Higher tier endocrine-disruptor testing should include fish development and fish reproduction tests, whereas a full life-cycle test could be subsequently used to refine aquatic risk assessments when necessary. For avian risk assessment, the new OECD Japanese quail reproduction test guideline provides a valuable basis for developing a test to detecting endocrine-mediated reproductive effects; this species could be used, where necessary, for an avian life-cycle test. For aquatic and terrestrial invertebrates, data from existing developmental and reproductive tests remain of high value for ecological risk assessment. High priority should be given to research into comparative endocrine physiology of invertebrates to support data extrapolation to this diverse fauna. PMID:11102288

  14. Screening breeding sites of the common toad (Bufo bufo) in England and Wales for evidence of endocrine disrupting activity.

    PubMed

    Pickford, Daniel B; Jones, Alexandra; Velez-Pelez, Alejandra; Orton, Frances; Iguchi, Taisen; Mitsui, Naoko; Tooi, Osamu

    2015-07-01

    Anuran amphibians are often present in agricultural landscapes and may therefore be exposed to chemicals in surface waters used for breeding. We used passive accumulation devices (SPMD and POCIS) to sample contaminants from nine breeding sites of the Common toad (Bufo bufo) across England and Wales, measuring endocrine activity of the extracts in a recombinant yeast androgen screen (YAS) and yeast estrogen screen (YES) and an in vitro vitellogenin induction screen in primary culture of Xenopus laevis hepatocytes. We also assessed hatching, growth, survival, and development in caged larvae in situ, and sampled metamorphs for gonadal histopathology. None of the SPMD extracts exhibited estrogen receptor or androgen receptor agonist activity, while POCIS extracts from two sites in west-central England exhibited concentration-dependent androgenic activity in the YAS. Three sites exhibited significant estrogenic activity in both the YES and the Xenopus hepatocyte. Hatching rates varied widely among sites, but there was no consistent correlation between hatching rate and intensity of agricultural activity, predicted concentrations of agrochemicals, or endocrine activity measured in YES/YAS assays. While a small number of intersex individuals were observed, their incidence could not be associated with predicted pesticide exposure or endocrine activitity measured in the in vitro screens. There were no significant differences in sex ratio, as determined by gonadal histomorphology among the study sites, and no significant correlation was observed between proportion of males and predicted exposure to agrochemicals. However, a negative correlation did become apparent in later sampling periods between proportion of males and estrogenic activity of the POCIS sample, as measured in the YES. Our results suggest that larval and adult amphibians may be exposed to endocrine disrupting chemicals in breeding ponds, albeit at low concentrations, and that chemical contaminants other than

  15. Detection of endocrine active substances in the aquatic environment in southern Taiwan using bioassays and LC-MS/MS.

    PubMed

    Chen, Kuang-Yu; Chou, Pei-Hsin

    2016-06-01

    Endocrine active substances, including naturally occurring hormones and various synthetic chemicals have received much concern owing to their endocrine disrupting potencies. It is essential to monitor their environmental occurrence since these compounds may pose potential threats to biota and human health. In this study, yeast-based reporter assays were carried out to investigate the presence of (anti-)androgenic, (anti-)estrogenic, and (anti-)thyroid compounds in the aquatic environment in southern Taiwan. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was also used to measure the environmental concentrations of selected endocrine active substances for assessing potential ecological risks and characterizing contributions to the endocrine disrupting activities. Bioassay results showed that anti-androgenic (ND-7489 μg L(-1) flutamide equivalent), estrogenic (ND-347 ng L(-1) 17β-estradiol equivalent), and anti-thyroid activities were detected in the dissolved and particulate phases of river water samples, while anti-estrogenic activities (ND-10 μg L(-1) 4-hydroxytamoxifen equivalent) were less often found. LC-MS/MS analysis revealed that anti-androgenic and estrogenic contaminants, such as bisphenol A, triclosan, and estrone were frequently detected in Taiwanese rivers. In addition, their risk quotient values were often higher than 1, suggesting that they may pose an ecological risk to the aquatic biota. Further identification of unknown anti-androgenic and estrogenic contaminants in Taiwanese rivers may be necessary to protect Taiwan's aquatic environment. PMID:26971174

  16. In vitro - in vivo correlations for endocrine activity of a mixture of currently used pesticides

    SciTech Connect

    Taxvig, Camilla; Hadrup, Niels; Boberg, Julie; Axelstad, Marta; Bossi, Rossana; Bonefeld-Jørgensen, Eva Cecilie; Vinggaard, Anne Marie

    2013-11-01

    Two pesticide mixtures were investigated for potential endocrine activity. Mix 3 consisted of bitertanol, propiconazole, and cypermethrin, and Mix 5 included malathion and terbuthylazine in addition to the three pesticides in Mix 3. All five single pesticides and the two mixtures were investigated for their ability to affect steroidogenesis in vitro in H295R cells. The pesticides alone and both mixtures affected steroidogenesis with both mixtures causing increase in progesterone and decrease in testosterone. For Mix 5 an increase in estradiol was seen as well, indicating increased aromatase activity. The two mixtures were also investigated in pregnant rats dosed from gestational day 7 to 21, followed by examination of dams and fetuses. Decreased estradiol and reduced placental testosterone were seen in dams exposed to Mix 5. Also a significant increase in aromatase mRNA-levels in female adrenal glands was found for Mix5. However, either of the two mixtures showed any effects on fetal hormone levels in plasma or testis, or on anogenital distance. Overall, potential aromatase induction was found for Mix 5 both in vitro and in vivo, but not for Mix 3, an effect likely owed to terbuthylazine in Mix 5. However, the hormonal responses in vitro were only partly reflected in vivo, probably due to some toxicokinetic issues, as the pesticide levels in the amniotic fluid also were found to be negatively affected by the number of compounds present in the mixtures. Nonetheless, the H295R assay gives hints on conceivable interference with steroidogenesis, thus generating hypotheses on in vivo effects. - Highlights: • The study examines the endocrine disrupting potential of mixtures of pesticides. • All single pesticides and both mixtures affected steroidogenesis in vitro. • Potential aromatase induction was found for Mix 5 both in vitro and in vivo. • The hormonal responses in vitro were only partly reflected in vivo.

  17. Endocrine glands

    MedlinePlus

    The endocrine system is primarily composed of glands that produce chemical messengers called hormones. Glands of the endocrine system include the pituitary gland, the thyroid gland, the parathyroid glands, the thymus, ...

  18. In vitro metabolism and bioavailability tests for endocrine active substances: What is needed next for regulatory purposes?

    EPA Science Inventory

    Legistation and prospective legislative proposals internationally (may) require that chemicals be tested for their ability to disrupt the hormonal systems of mammals. Chemicals found to test positive in vitro are considered to be endocrine active substances (EAS) and may be puta...

  19. THE INFLUENCE OF SERUM BINDING PROTEINS AND CLEARANCE ON THE COMPARATIVE RECEPTOR BINDING POTENCY OF ENDOCRINE ACTIVE COMPOUNDS

    EPA Science Inventory

    THE INFLUENCE OF SERUM BINDING PROTEINS AND CLEARANCE ON THE COMPARATIVE RECEPTOR BINDING POTENCY OF ENDOCRINE ACTIVE COMPOUNDS. JG Teeguarden1 and HA Barton2. 1ENVIRON International, Ruston LA; 2US EPA, ORD, NHEERL, ETD, Pharmacokinetics Branch, RTP, NC.

    One measure of th...

  20. A review of the endocrine activity of parabens and implications for potential risks to human health.

    PubMed

    Golden, Robert; Gandy, Jay; Vollmer, Guenter

    2005-06-01

    Parabens are a group of the alkyl esters of p-hydroxybenzoic acid and typically include methylparaben, ethylparaben, propylparaben, butylparaben, isobutylparaben, isopropylparaben, and benzylparaben. Parabens (or their salts) are widely used as preservatives in cosmetics, toiletries, and pharmaceuticals due to their relatively low toxicity profile and a long history of safe use. Testing of parabens has revealed to varying degrees that individual paraben compounds have weakly estrogenic activity in some in vitro screening tests, such as ligand binding to the estrogen receptor, regulation of CAT gene expression, and proliferation of MCF-7 cells. Reported in vivo effects include increased uterine weight (i.e., butyl-, isobutyl-, and benzylparaben) and male reproductive-tract effects (i.e., butyl- and propylparaben). However, in relation to estrogen as a control during in vivo studies, the parabens with activity are many orders of magnitude less active than estrogen. While exposure to sufficient doses of exogenous estrogen can increase the risk of certain adverse effects, the presumption that similar risks might also result from exposure to endocrine-active chemicals (EACs) with far weaker activity is still speculative. In assessing the likelihood that exposure to weakly active EACs might be etiologically associated with adverse effects due to an endocrine-mediated mode of action, it is paramount to consider both the doses and the potency of such compounds in comparison with estrogen. In this review, a comparative approach involving both dose and potency is used to assess whether in utero or adult exposure to parabens might be associated with adverse effects mediated via an estrogen-modulating mode of action. In utilizing this approach, the paraben doses required to produce estrogenic effects in vivo are compared with the doses of either 17beta-estradiol or diethylstilbestrol (DES) that are well established in their ability to affect endocrine activity. Where possible

  1. Biological regulation of receptor-hormone complex concentrations in relation to dose-response assessments for endocrine-active compounds.

    PubMed

    Andersen, M E; Barton, H A

    1999-03-01

    Some endocrine-active compounds (EACs) act as agonists or antagonists of specific hormones and may interfere with cellular control processes that regulate gene transcription. Many mechanisms controlling gene expression are universal to organisms ranging from unicellular bacteria to more complex plants and animals. One mechanism, coordinated control of batteries of gene products, is critical in adaptation of bacteria to new environments and for development and tissue differentiation in multi-cellular organisms. To coordinately activate sets of genes, all living organisms have devised molecular modules to permit transitions, or switching, between different functional states over a small range of hormone concentration, and other modules to stabilize the new state through homeostatic interactions. Both switching and homeostasis are regulated by controlling concentrations of hormone-receptor complexes. Molecular control processes for switching and homeostasis are inherently nonlinear and often utilize autoregulatory feedback loops. Among the biological processes contributing to switching phenomena are receptor autoinduction, induction of enzymes for ligand synthesis, mRNA stabilization/activation, and receptor polymerization. This paper discusses a variety of molecular switches found in animal species, devises simple quantitative models illustrating roles of specific molecular interactions in creating switching modules, and outlines the impact of these switching processes and other feedback loops for risk assessments with EACs. Quantitative simulation modeling of these switching mechanisms made it apparent that highly nonlinear dose-response curves for hormones and EACs readily arise from interactions of several linear processes acting in concert on a common control point. These nonlinear mechanisms involve amplification of response, rather than multimeric molecular interactions as in conventional Hill relationships. PMID:10330682

  2. The enhancement of the subacute repeat dose toxicity test OECD TG 407 for the detection of endocrine active chemicals: comparison with toxicity tests of longer duration.

    PubMed

    Gelbke, Heinz-Peter; Hofmann, Andreas; Owens, J William; Freyberger, Alexius

    2007-04-01

    The OECD conventional 28-day repeat dose toxicity test (OECD TG 407) is widely employed in the initial hazard identification and characterization for commercial chemicals. The OECD has recently undertaken an international effort to "enhance" the conventional 28-day repeat dose toxicity test (OECD TG 407) in order to ensure that chemicals acting through (anti)estrogenic, (anti)androgenic, and (anti)thyroid mechanisms are identified. The enhancements include additional parameters based on the respective target organs from the male and female reproductive tracts, the thyroid, and circulating hormone levels. Ten chemicals with known endocrine modes of action and different potencies were administered using the "enhanced TG 407" test protocol to investigate the performance of this procedure. In the present evaluation, these "enhanced TG 407" protocol results, drawn from a report of the OECD validation studies, are compared to studies of the same or similar chemicals with longer and/or in utero exposures in order to evaluate the capability of the this "enhanced TG 407" in identifying the chemicals' mode of action. The major conclusions that can be drawn from these comparisons are: 1. The "enhanced TG 407" will reliably identify chemicals with a strong to moderate potential to act through endocrine modes of action on the gonads and the thyroid. In addition, this test method gives a first indication for the dose-related potency. 2. Substances with a low potency for an endocrine mode of action, i.e., having only marginal effects in the most comprehensive in vivo studies such as multi-generation studies, may not elicit clear endocrine-related effects in the "enhanced TG 407". In these cases, the primary or principal effects observed will be driven by other toxic actions of the test materials in the "enhanced TG 407". 3. It may be concluded from the present database that prolongation of exposure from 28 days up to 90 days is unlikely to improve the chance of detecting an

  3. Evaluation of a two-generation reproduction toxicity study adding endpoints to detect endocrine disrupting activity using lindane.

    PubMed

    Matsuura, Ikuo; Saitoh, Tetsuji; Tani, Einosuke; Wako, Yumi; Iwata, Hiroshi; Toyota, Naoto; Ishizuka, Yoshihito; Namiki, Masato; Hoshino, Nobuhito; Tsuchitani, Minoru; Ikeda, Yasuo

    2005-12-01

    A two-generation reproduction toxicity study in rats adding extra endpoints to detect endocrine disrupting activity was conducted using lindane by dietary administration at 0, 10, 60, and 300 ppm, for investigation of its utility. The extra endpoints included anogenital distance (AGD), nipple development, sexual maturation (vaginal opening and preputial separation), estrous cycle, spermatogenesis, sex organ weights, and blood hormone concentrations (thyroid and sex hormones). F1 offspring were examined for emotionality (open field test), motor coordination (rotarod test), as well as learning and memory (pole-climbing test). Hepatic drug-metabolizing enzyme activities were also measured. The results revealed general toxicological effects on parental animals, influence on reproductive function, and altered development of offspring; however, they did not demonstrate any distinct changes in the extra endpoints for detection of endocrine disrupting activity. Adult toxicity was observed in both F0 and F1 animals, including suppressed body weight gain and reduced food consumption in both sexes, and deaths of females at 300 ppm. Convulsions and irritability were observed during the perinatal period in pregnant F1 females given 300 ppm. Pathological examination revealed increased liver weights and centrilobular hepatocellular hypertrophy in both sexes and generations at 10 or 60 ppm and above; in addition, increased kidney weights and increased hyaline droplets in the proximal tubule epithelium, and basophilic renal tubules in males were noted at 10 ppm and above. Pituitary weights were decreased in F0 females and in F1 males and females and adrenal weights were increased in F1 males and females at 300 ppm; however, no histological changes were observed, and manifestations suggesting endocrine disrupting activity related to these changes were lacking. Hypertrophy of the thyroid follicular epithelium in F0 females at 300 ppm and in F1 males at 60 and 300 ppm, and decreases

  4. Detection and evaluation of endocrine-disruption activity in water samples from Portuguese rivers.

    PubMed

    Quirós, Laia; Céspedes, Raquel; Lacorte, Sílvia; Viana, Paula; Raldúa, Demetrio; Barceló, Damià; Piña, Benjamin

    2005-02-01

    Water samples (n = 183) from Portuguese rivers were tested for the presence of endocrine disruptors using the recombinant yeast assay (RYA) combined with chemical identification of compounds having endocrine-disruption properties by liquid chromatography coupled to mass spectrometry. Ten selected locations were sampled monthly for a period of 20 months, from April 2001 to December 2002. More than 90% of samples showed either no detectable or low levels of estrogenicity (<0.1 ng/L of estradiol equivalents). The remaining samples (17 in total, 9.3%) showed estrogenicity values ranging from 0.1 to 1.7 ng/L of estradiol equivalents; only two samples showed values greater than 1 ng/L of estradiol equivalents. Most highly estrogenic samples (13 of 17 samples) originated in five sampling sites clustered in two zones near Porto and Lisbon. Chemical analysis detected alkylphenolic compounds (octyl- and nonylphenol plus nonylphenol ethoxylates) in all samples, albeit at concentrations less than 1 microg/L for each compound in 80% of samples. Total analyte concentration exceeded 10 microg/L in only 10 samples, with all but one of those originating from only two sampling sites. In these two locations, a good correlation was observed between the concentrations of octylphenol, nonylphenol, and to a lesser extent, bisphenol A in the samples and their estrogenicity values as calculated by RYA. We conclude that estrogenic activity can be explained by alkylphenol contamination in only these sites; for the remainder, we propose that pesticides and urban waste may be the main factors responsible for estrogenic contamination. PMID:15719999

  5. Exploring potential contributors to endocrine disrupting activities in Taiwan's surface waters using yeast assays and chemical analysis.

    PubMed

    Chou, Pei-Hsin; Lin, Yi-Ling; Liu, Tong-Cun; Chen, Kuang-Yu

    2015-11-01

    Surface waters serve as sinks for anthropogenic contaminants, including naturally occurring hormones and a variety of synthetic endocrine active substances. To investigate the presence of endocrine active contaminants in the aquatic environment in Taiwan, river water and suspended solids were analyzed by yeast assays to examine the distribution of estrogenic, androgenic, and aryl hydrocarbon receptor agonist activities. The results showed that dry-season river samples exhibited strong estrogenic and aryl hydrocarbon receptor agonist activities, but no androgenic activity was detected. Owing to the ubiquitous detection of estrogenic activities in Taiwan's surface waters, samples were further subjected to liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis for quantification of selected estrogenic compounds. LC-MS/MS results indicated that natural estrogens, such as estrone and 17β-estradiol were often the most contributing compounds for the bioassay-derived estrogenic activities due to their strong estrogenic potencies and high detection frequencies, whereas high concentrations of bisphenol A and nonylphenol also posed a threat to the aquatic ecosystems in Taiwan. Water samples eliciting strong estrogenic activities were further fractionated using high performance liquid chromatography, and significant estrogenic activities were detected in fractions containing estrone, 17β-estradiol, 17α-ethynylestradiol, and bisphenol A. Also, the presence of unidentified estrogenic compounds was found in few river water samples. Further identification of unknown endocrine active substances is necessary to better protect the aquatic environment in Taiwan. PMID:26295540

  6. QSAR classification models for the prediction of endocrine disrupting activity of brominated flame retardants.

    PubMed

    Kovarich, Simona; Papa, Ester; Gramatica, Paola

    2011-06-15

    The identification of potential endocrine disrupting (ED) chemicals is an important task for the scientific community due to their diffusion in the environment; the production and use of such compounds will be strictly regulated through the authorization process of the REACH regulation. To overcome the problem of insufficient experimental data, the quantitative structure-activity relationship (QSAR) approach is applied to predict the ED activity of new chemicals. In the present study QSAR classification models are developed, according to the OECD principles, to predict the ED potency for a class of emerging ubiquitary pollutants, viz. brominated flame retardants (BFRs). Different endpoints related to ED activity (i.e. aryl hydrocarbon receptor agonism and antagonism, estrogen receptor agonism and antagonism, androgen and progesterone receptor antagonism, T4-TTR competition, E2SULT inhibition) are modeled using the k-NN classification method. The best models are selected by maximizing the sensitivity and external predictive ability. We propose simple QSARs (based on few descriptors) characterized by internal stability, good predictive power and with a verified applicability domain. These models are simple tools that are applicable to screen BFRs in relation to their ED activity, and also to design safer alternatives, in agreement with the requirements of REACH regulation at the authorization step.

  7. Adsorption of selected pharmaceuticals and an endocrine disrupting compound by granular activated carbon. 2. Model prediction

    SciTech Connect

    Yu, Z.; Peldszus, S.; Huck, P.M.

    2009-03-01

    The adsorption of two representative pharmaceutically active compounds (PhACs) naproxen and carbamazepine and one endocrine disrupting compound (EDC) nonylphenol was studied in pilot-scale granular activated carbon (GAC) adsorbers using post-sedimentation (PS) water from a full-scale drinking water treatment plant. The GAC adsorbents were coal-based Calgon Filtrasorb 400 and coconut shell-based PICA CTIF TE. Acidic naproxen broke through fastest while nonylphenol was removed best, which was consistent with the degree to which fouling affected compound removals. Model predictions and experimental data were generally in good agreement for all three compounds, which demonstrated the effectiveness and robustness of the pore and surface diffusion model (PSDM) used in combination with the time-variable parameter approach for predicting removals at environmentally relevant concentrations (i.e., ng/L range). Sensitivity analyses suggested that accurate determination of film diffusion coefficients was critical for predicting breakthrough for naproxen and carbamazepine, in particular when high removals are targeted. Model simulations demonstrated that GAC carbon usage rates (CURs) for naproxen were substantially influenced by the empty bed contact time (EBCT) at the investigated conditions. Model-based comparisons between GAC CURs and minimum CURs for powdered activated carbon (PAC) applications suggested that PAC would be most appropriate for achieving 90% removal of naproxen, whereas GAC would be more suitable for nonylphenol. 25 refs., 4 figs., 1 tab.

  8. Adsorption of selected pharmaceuticals and an endocrine disrupting compound by granular activated carbon. 2. Model prediction.

    PubMed

    Yu, Zirui; Peldszus, Sigrid; Huck, Peter M

    2009-03-01

    The adsorption of two representative pharmaceutically active compounds (PhACs)-naproxen and carbamazepine and one endocrine disrupting compound (EDC)-nonylphenol was studied in pilot-scale granular activated carbon (GAC) adsorbers using post-sedimentation (PS) water from a full-scale drinking water treatment plant. Acidic naproxen broke through fastest while nonylphenol was removed best, which was consistent with the degree to which fouling affected compound removals. Model predictions and experimental data were generally in good agreement for all three compounds, which demonstrated the effectiveness and robustness of the pore and surface diffusion model (PSDM) used in combination with the time-variable parameter approach for predicting removals at environmentally relevant concentrations (i.e., ng/L range). Sensitivity analyses suggested that accurate determination of film diffusion coefficients was critical for predicting breakthrough for naproxen and carbamazepine, in particular when high removals are targeted. Model simulations demonstrated that GAC carbon usage rates (CURs) for naproxen were substantially influenced by the empty bed contact time (EBCT) at the investigated conditions. Model-based comparisons between GAC CURs and minimum CURs for powdered activated carbon (PAC) applications suggested that PAC would be most appropriate for achieving 90% removal of naproxen, whereas GAC would be more suitable for nonylphenol. PMID:19350922

  9. Thirty years of the heart as an endocrine organ: physiological role and clinical utility of cardiac natriuretic hormones.

    PubMed

    Clerico, Aldo; Giannoni, Alberto; Vittorini, Simona; Passino, Claudio

    2011-07-01

    Thirty years ago, De Bold et al. (20) reported that atrial extracts contain some biologically active peptides, which promote a rapid and massive diuresis and natriuresis when injected in rats. It is now clear that the heart also exerts an endocrine function and in this way plays a key role in the regulation of cardiovascular and renal systems. The aim of this review is to discuss some recent insights and still-debated findings regarding the cardiac natriuretic hormones (CNHs) produced and secreted by cardiomyocytes (i.e., atrial natriuretic peptide and B-type natriuretic peptide). The functional status of the CNH system depends not only on the production/secretion of CNHs by cardiomyocytes but also on both the peripheral activation of circulating inactive precursor of natriuretic hormones and the transduction of the hormone signal by specific receptors. In this review, we will discuss the data supporting the hypothesis that the production and secretion of CNHs is the result of a complex integration among mechanical, chemical, hemodynamic, humoral, ischemic, and inflammatory inputs. The cross talk among endocrine function, adipose tissue, and sex steroid hormones will be discussed more in detail, considering the clinically relevant relationships linking together cardiovascular risk, sex, and body fat development and distribution. Finally, we will review the pathophysiological role and the clinical relevance of both peripheral maturation of the precursor of B-type natriuretic peptides and hormone signal transduction.

  10. Do laboratory species protect endangered species? Interspecies variation in responses to 17β-estradiol, a model endocrine active compound

    USGS Publications Warehouse

    Jorgenson, Zachary G.; Buhl, Kevin J.; Bartell, Stephen E.; Schoenfuss, Heiko L.

    2015-01-01

    Although the effects of estrogens on model laboratory species are well documented, their utility as surrogates for other species, including those listed as endangered, are less clear. Traditionally, conservation policies are evaluated based on model organism responses but are intended to protect all species in an environment. We tested the hypothesis that the endangered Rio Grande silvery minnow (Hybognathus amarus) is more vulnerable to endocrine disruption—as assessed through its larval predator-escape performance, survival, juvenile sex ratios, and whole-body vitellogenin concentration—than the commonly used toxicological model species fathead minnow (Pimephales promelas) and the bluegill sunfish (Lepomis macrochirus). Fish were exposed concurrently for 21 days to the model endocrine active compound (EAC) 17ß-estradiol (E2) at 10 ng E2/L and 30 ng E2/L in a flow-through system using reconstituted water that simulated the physicochemical conditions of the Middle Rio Grande in New Mexico, USA. No significant differences were observed between the fathead and silvery minnow in larval predator-escape response or juvenile sex ratio. Rio Grande silvery minnow survival decreased significantly at day 14 compared with the other two species; by day 21, both cyprinid species (silvery minnow and fathead minnow) exhibited a significant decrease in survival compared with bluegill sunfish, a member of the family Centrarchidae. Male Rio Grande silvery minnow showed a significant increase in whole-body vitellogenin concentration in the 10 ng/L treatment, whereas fathead minnow and bluegill sunfish showed no significant increases in vitellogenin concentrations across treatments. Our study showed response differences to estrogen exposures between the two cyprinid species and further divergence in responses between the families Cyprinidae and Centrarchidae. These results suggest that commonly used laboratory model organisms may be less sensitive to EACs than the endangered

  11. Do laboratory species protect endangered species? Interspecies variation in responses to 17β-estradiol, a model endocrine active compound.

    PubMed

    Jorgenson, Z G; Buhl, K; Bartell, S E; Schoenfuss, H L

    2015-01-01

    Although the effects of estrogens on model laboratory species are well documented, their utility as surrogates for other species, including those listed as endangered, are less clear. Traditionally, conservation policies are evaluated based on model organism responses but are intended to protect all species in an environment. We tested the hypothesis that the endangered Rio Grande silvery minnow (Hybognathus amarus) is more vulnerable to endocrine disruption-as assessed through its larval predator-escape performance, survival, juvenile sex ratios, and whole-body vitellogenin concentration-than the commonly used toxicological model species fathead minnow (Pimephales promelas) and the bluegill sunfish (Lepomis macrochirus). Fish were exposed concurrently for 21 days to the model endocrine active compound (EAC) 17ß-estradiol (E2) at 10 ng E2/L and 30 ng E2/L in a flow-through system using reconstituted water that simulated the physicochemical conditions of the Middle Rio Grande in New Mexico, USA. No significant differences were observed between the fathead and silvery minnow in larval predator-escape response or juvenile sex ratio. Rio Grande silvery minnow survival decreased significantly at day 14 compared with the other two species; by day 21, both cyprinid species (silvery minnow and fathead minnow) exhibited a significant decrease in survival compared with bluegill sunfish, a member of the family Centrarchidae. Male Rio Grande silvery minnow showed a significant increase in whole-body vitellogenin concentration in the 10 ng/L treatment, whereas fathead minnow and bluegill sunfish showed no significant increases in vitellogenin concentrations across treatments. Our study showed response differences to estrogen exposures between the two cyprinid species and further divergence in responses between the families Cyprinidae and Centrarchidae. These results suggest that commonly used laboratory model organisms may be less sensitive to EACs than the endangered Rio

  12. Identification of California Condor Estrogen Receptors 1 and 2 and Their Activation by Endocrine Disrupting Chemicals.

    PubMed

    Felton, Rachel G; Steiner, Cynthia C; Durrant, Barbara S; Keisler, Duane H; Milnes, Matthew R; Tubbs, Christopher W

    2015-12-01

    Recently, California condors (Gymnogyps californianus) have been reintroduced to coastal regions of California where they feed on marine mammal carcasses. There is evidence that coastal-dwelling condors experience reproductive issues, such as eggshell thinning, likely resulting from exposure to endocrine-disrupting chemicals (EDCs). To address this problem, we have identified and cloned condor estrogen receptors (ESRs) 1 and 2 and characterized their activation by EDCs present in the coastal habitats where condors reside. Dichlorodiphenyltrichloroethane (DDT) and its metabolites all activated ESR1 and ESR2, although their relative potency differed between the receptors. Bisphenol A, dieldrin, trans-nonachlor, and polychlorinated biphenyl 52 (PCB52) moderately activated both ESRs, whereas PCB138 and PCB153 stimulated little to no activation. Overall, EDC activation of condor ESR2, which is the first ESR2 cloned from a raptor species, was greater than that of ESR1. Significant activation of both condor ESRs by EDCs occurred at high concentrations (≥1μM), which are within the range of plasma levels of certain EDCs (eg, dichlorodiphenyldichloroethylene [p'p-DDE]) in coastal-dwelling condors. Finally, phylogenetic analyses of ESRs of 41 avian species identified a single amino acid position in ESR2 under positive selection. Mutation of this amino acid affected receptor activation by EDCs, suggesting the identity of this amino acid may influence EDC sensitivity of avian species. Together, these findings broaden our understanding of EDC interactions with ESRs in avian species. For condors specifically, these data could be used to evaluate EDC exposure risk at future release sites to identify those least likely to compromise the continued recovery of this species.

  13. Identification of California Condor Estrogen Receptors 1 and 2 and Their Activation by Endocrine Disrupting Chemicals.

    PubMed

    Felton, Rachel G; Steiner, Cynthia C; Durrant, Barbara S; Keisler, Duane H; Milnes, Matthew R; Tubbs, Christopher W

    2015-12-01

    Recently, California condors (Gymnogyps californianus) have been reintroduced to coastal regions of California where they feed on marine mammal carcasses. There is evidence that coastal-dwelling condors experience reproductive issues, such as eggshell thinning, likely resulting from exposure to endocrine-disrupting chemicals (EDCs). To address this problem, we have identified and cloned condor estrogen receptors (ESRs) 1 and 2 and characterized their activation by EDCs present in the coastal habitats where condors reside. Dichlorodiphenyltrichloroethane (DDT) and its metabolites all activated ESR1 and ESR2, although their relative potency differed between the receptors. Bisphenol A, dieldrin, trans-nonachlor, and polychlorinated biphenyl 52 (PCB52) moderately activated both ESRs, whereas PCB138 and PCB153 stimulated little to no activation. Overall, EDC activation of condor ESR2, which is the first ESR2 cloned from a raptor species, was greater than that of ESR1. Significant activation of both condor ESRs by EDCs occurred at high concentrations (≥1μM), which are within the range of plasma levels of certain EDCs (eg, dichlorodiphenyldichloroethylene [p'p-DDE]) in coastal-dwelling condors. Finally, phylogenetic analyses of ESRs of 41 avian species identified a single amino acid position in ESR2 under positive selection. Mutation of this amino acid affected receptor activation by EDCs, suggesting the identity of this amino acid may influence EDC sensitivity of avian species. Together, these findings broaden our understanding of EDC interactions with ESRs in avian species. For condors specifically, these data could be used to evaluate EDC exposure risk at future release sites to identify those least likely to compromise the continued recovery of this species. PMID:26372180

  14. The pleiotropic roles of transforming growth factor beta inhomeostasis and carcinogenesis of endocrine organs.

    SciTech Connect

    Fleisch, Markus C.; Maxwell, Christopher A.; Barcellos-Hoff,Mary-Helen

    2006-01-13

    Transforming growth factor beta (TGF-beta) is a ubiquitous cytokine that plays a critical role in numerous pathways regulating cellular and tissue homeostasis. TGF-beta is regulated by hormones and is a primary mediator of hormone response in uterus, prostate and mammary gland. This review will address the role of TGF-beta in regulating hormone dependent proliferation and morphogenesis. The subversion of TGF-beta regulation during the processes of carcinogenesis, with particular emphasis on its effects on genetic stability and epithelial to mesenchymal transition (EMT), will also be examined. An understanding of the multiple and complex mechanisms of TGF-beta regulation of epithelial function, and the ultimate loss of TGF-beta function during carcinogenesis, will be critical in the design of novel therapeutic interventions for endocrine-related cancers.

  15. Relationships of putative endocrine disruptors to human sexual maturation and thyroid activity in youth

    PubMed Central

    Schell, Lawrence M.; Gallo, Mia V.

    2009-01-01

    Endocrine disruption has become a significant human health concern, but is difficult to study outside of the laboratory for several reasons including the multiplicity of exposures, the difficulty in assessing each exposure, and the variety of possible outcomes among human populations. This review summarizes our studies of the relationships of measured persistent organic pollutants (PCBs, p,p′-DDE, HCB and mirex), and heavy metals (lead and mercury), to outcomes directly related to thyroid function and sexual maturation. These studies were conducted in a sample of Native American youth from the Akwesasne Mohawk community. The participants were first studied during puberty (10–16.9 years of age) and then at approximately 18 years of age. Results from these studies show that PCB levels are positively related to TSH and negatively to free T4. Further, these effects are conditioned by breastfeeding history. Anti-thyroid peroxidase antibody levels also are related to PCB levels suggesting elevated risk of autoimmune disease among the exposed. Earlier age at menarche is associated with higher PCB levels while risk of delay is associated with higher lead levels. Some evidence that the timing of exposure produces different effects is presented, and the level of exposure in the participants suggests that effects observed may be relevant to a considerable proportion of the US population. Further investigations are warranted to determine effect thresholds and mechanisms. PMID:19800354

  16. Structural features of endocrine active chemicals--A comparison of in vivo and in vitro data.

    PubMed

    Lewin, Geertje; Escher, Sylvia E; van der Burg, Bart; Simetska, Nelly; Mangelsdorf, Inge

    2015-08-01

    Studies on reproductive toxicity need high numbers of test animals. Therefore, we investigated whether chemical structural features (SF) in combination with in vitro data on specific adverse outcome pathways (AOPs) may be used for predicting reproductive toxicity of untested chemicals. Using the OECD Toolbox and expert judgment, we identified 89 structure groups for 275 chemicals for which the results of prenatal developmental toxicity or multigeneration studies were present in the Fraunhofer database on Fertility and Developmental Toxicity in experimental animals (FeDTex) database. Likewise, we evaluated 220 chemicals which had been tested in reporter gene assays on endocrine ((anti)estrogenic and (anti)androgenic) properties in the CALUX(®) test battery. There was a large spread of effect levels for substances within the chemical structure groups for both, in vivo and in vitro results. The groups of highest concern (diphenyl derivatives, planar conjugated systems with fused rings, phenols and organophosphates) correlated quite well, however, between the in vivo and in vitro data on estrogenic activity. For the 56 chemicals represented in both databases, lowest effect doses in vivo correlated well with the estrogenic activity in vitro. These results suggest that a panel of assays covering relevant AOPs and data on metabolism and toxicokinetics may allow prediction of relative reproductive or development toxicity potency within the identified chemical structure groups.

  17. Measuring Endocrine-active Chemicals at ng/L Concentrations in Water

    EPA Science Inventory

    Analytical chemistry challenges for supporting aquatic toxicity research and risk assessment are many: need for low detection limits, complex sample matrices, small sample size, and equipment limitations to name a few. Certain types of potent endocrine disrupting chemicals (EDCs)...

  18. Perfluorooctane sulfonate (PFOS) affects hormone receptor activity, steroidogenesis, and expression of endocrine-related genes in vitro and in vivo.

    PubMed

    Du, Guizhen; Hu, Jialei; Huang, Hongyu; Qin, Yufeng; Han, Xiumei; Wu, Di; Song, Ling; Xia, Yankai; Wang, Xinru

    2013-02-01

    Perfluorooctane sulfonate (PFOS) is a widespread and persistent chemical in the environment. We investigated the endocrine-disrupting effects of PFOS using a combination of in vitro and in vivo assays. Reporter gene assays were used to detect receptor-mediated (anti-)estrogenic, (anti-)androgenic, and (anti-)thyroid hormone activities. The effect of PFOS on steroidogenesis was assessed both at hormone levels in the supernatant and at expression levels of hormone-induced genes in the H295R cell. A zebrafish-based short-term screening method was developed to detect the effect of PFOS on endocrine function in vivo. The results indicate that PFOS can act as an estrogen receptor agonist and thyroid hormone receptor antagonist. Exposure to PFOS decreased supernatant testosterone (T), increased estradiol (E2) concentrations in H295R cell medium and altered the expression of several genes involved in steroidogenesis. In addition, PFOS increased early thyroid development gene (hhex and pax8) expression in a concentration-dependent manner, decreased steroidogenic enzyme gene (CYP17, CYP19a, CYP19b) expression, and changed the expression pattern of estrogen receptor production genes (esr1, esr2b) after 500 µg/L PFOS treatment in zebrafish embryos. These results indicate that PFOS has the ability to act as an endocrine disruptor both in vitro and in vivo by disrupting the function of nuclear hormone receptors, interfering with steroidogenesis, and altering the expression of endocrine-related genes in zebrafish embryo.

  19. Perfluorooctane sulfonate (PFOS) affects hormone receptor activity, steroidogenesis, and expression of endocrine-related genes in vitro and in vivo.

    PubMed

    Du, Guizhen; Hu, Jialei; Huang, Hongyu; Qin, Yufeng; Han, Xiumei; Wu, Di; Song, Ling; Xia, Yankai; Wang, Xinru

    2013-02-01

    Perfluorooctane sulfonate (PFOS) is a widespread and persistent chemical in the environment. We investigated the endocrine-disrupting effects of PFOS using a combination of in vitro and in vivo assays. Reporter gene assays were used to detect receptor-mediated (anti-)estrogenic, (anti-)androgenic, and (anti-)thyroid hormone activities. The effect of PFOS on steroidogenesis was assessed both at hormone levels in the supernatant and at expression levels of hormone-induced genes in the H295R cell. A zebrafish-based short-term screening method was developed to detect the effect of PFOS on endocrine function in vivo. The results indicate that PFOS can act as an estrogen receptor agonist and thyroid hormone receptor antagonist. Exposure to PFOS decreased supernatant testosterone (T), increased estradiol (E2) concentrations in H295R cell medium and altered the expression of several genes involved in steroidogenesis. In addition, PFOS increased early thyroid development gene (hhex and pax8) expression in a concentration-dependent manner, decreased steroidogenic enzyme gene (CYP17, CYP19a, CYP19b) expression, and changed the expression pattern of estrogen receptor production genes (esr1, esr2b) after 500 µg/L PFOS treatment in zebrafish embryos. These results indicate that PFOS has the ability to act as an endocrine disruptor both in vitro and in vivo by disrupting the function of nuclear hormone receptors, interfering with steroidogenesis, and altering the expression of endocrine-related genes in zebrafish embryo. PMID:23074026

  20. Plasticity of renal endocrine function.

    PubMed

    Kurt, Birgül; Kurtz, Armin

    2015-03-15

    The kidneys are important endocrine organs. They secrete humoral factors, such as calcitriol, erythropoietin, klotho, and renin into the circulation, and therefore, they are essentially involved in the regulation of a variety of processes ranging from bone formation to erythropoiesis. The endocrine functions are established by cells, such as proximal or distal tubular cells, renocortical interstitial cells, or mural cells of afferent arterioles. These endocrine cells are either fixed in number, such as tubular cells, which individually and gradually upregulate or downregulate hormone production, or they belong to a pool of cells, which display a recruitment behavior, such as erythropoietin- and renin-producing cells. In the latter case, regulation of humoral function occurs via (de)recruitment of active endocrine cells. As a consequence renin- and erythropoietin-producing cells in the kidney show a high degree of plasticity by reversibly switching between distinct cell states. In this review, we will focus on the characteristics of renin- and of erythropoietin-producing cells, especially on their origin and localization, their reversible transformations, and the mediators, which are responsible for transformation. Finally, we will discuss a possible interconversion of renin and erythropoietin expression. PMID:25608752

  1. Activation of the Maternal Immune System Induces Endocrine Changes in the Placenta via IL-6

    PubMed Central

    Hsiao, Elaine Y.; Patterson, Paul H.

    2011-01-01

    Activation of the maternal immune system in rodent models sets in motion a cascade of molecular pathways that ultimately result in autism- and schizophrenia-related behaviors in offspring. The finding that interleukin-6 (IL-6) is a crucial mediator of these effects led us to examine the mechanism by which this cytokine influences fetal development in vivo. Here we focus on the placenta as the site of direct interaction between mother and fetus and as a principal modulator of fetal development. We find that maternal immune activation (MIA) with a viral mimic, synthetic double-stranded RNA (poly(I:C)), increases IL-6 mRNA as well as maternally-derived IL-6 protein in the placenta. Placentas from MIA mothers exhibit increases in CD69+ decidual macrophages, granulocytes and uterine NK cells, indicating elevated early immune activation. Maternally-derived IL-6 mediates activation of the JAK/STAT3 pathway specifically in the spongiotrophoblast layer of the placenta, which results in expression of acute phase genes. Importantly, this parallels an IL-6-dependent disruption of the growth hormone-insulin-like growth factor (GH-IGF) axis that is characterized by decreased GH, IGFI and IGFBP3 levels. In addition, we observe an IL-6-dependent induction in pro-lactin-like protein-K (PLP-K) expression as well as MIA-related alterations in other placental endocrine factors. Together, these IL-6-mediated effects of MIA on the placenta represent an indirect mechanism by which MIA can alter fetal development. PMID:21195166

  2. Investigating apical adverse effects of four endocrine active substances in the freshwater gastropod Lymnaea stagnalis.

    PubMed

    Giusti, Arnaud; Lagadic, Laurent; Barsi, Alpar; Thomé, Jean-Pierre; Joaquim-Justo, Célia; Ducrot, Virginie

    2014-09-15

    The hermaphroditic gastropod Lymnaea stagnalis is proposed as a candidate species for the development of OECD guidelines for testing of the reprotoxicity of chemicals, including endocrine active substances (EASs). Up to now, only a few putative EASs have been tested for their reproductive toxicity in this species. In this study, we investigate the effects of four EASs with different affinities to the vertebrate estrogen and androgen receptors (chlordecone as an estrogen; cyproterone acetate, fenitrothion and vinclozolin as anti-androgens) on the reproduction of L. stagnalis in a 21-day semi-static test. Testosterone and 17α-ethinylestradiol (EE2) were used as the reference compounds. The tested EASs had no significant effect on growth and survival at the tested concentration ranges (ng to μg/L). Classical reproduction endpoints (i.e., oviposition and fecundity) were not responsive to the tested chemicals, except for chlordecone and 17α-ethinylestradiol, which hampered reproduction from 19.6 μg/L and 17.6 μg/L, respectively. The frequency of polyembryonic eggs, used as an additional endpoint, demonstrated the effects of all compounds except EE2. The molecular pathways, which are involved in such reproduction impairments, remain unknown. Our results suggest that egg quality is a more sensitive endpoint as compared to other reproductive endpoints commonly assessed in mollusk toxicity tests.

  3. Quantitative mechanistically based dose-response modeling with endocrine-active compounds.

    PubMed Central

    Andersen, M E; Conolly, R B; Faustman, E M; Kavlock, R J; Portier, C J; Sheehan, D M; Wier, P J; Ziese, L

    1999-01-01

    A wide range of toxicity test methods is used or is being developed for assessing the impact of endocrine-active compounds (EACs) on human health. Interpretation of these data and their quantitative use in human and ecologic risk assessment will be enhanced by the availability of mechanistically based dose-response (MBDR) models to assist low-dose, interspecies, and (italic)in vitro(/italic) to (italic)in vivo(/italic) extrapolations. A quantitative dose-response modeling work group examined the state of the art for developing MBDR models for EACs and the near-term needs to develop, validate, and apply these models for risk assessments. Major aspects of this report relate to current status of these models, the objectives/goals in MBDR model development for EACs, low-dose extrapolation issues, regulatory inertia impeding acceptance of these approaches, and resource/data needs to accelerate model development and model acceptance by the research and the regulatory community. PMID:10421774

  4. [Endocrine hypertension].

    PubMed

    Takeda, R

    1993-03-01

    Endocrine Hypertension, is, in a narrow sense, defined as adrenal hypertension, including mainly pheochromocytoma, Cushing's syndrome, a syndrome of primary aldosteronism and it's related mineralocorticoid excess disorders. In memory of a great contribution to hypertensiology by the late Prof. Murakami, who was the first author to write on pheochromocytoma in Japan, this paper is dedicated to reviewing the current status of adrenal hypertension in Japan from the epidemiological viewpoint, putting emphasis upon the clinical characteristics of aged patients with adrenal hypertension. Secondly, some topics in the research field of each adrenal hypertension are briefly introduced. Thirdly, our recent data are presented, showing 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) mRNA expression in resistance vessels and decreased 11 beta-HSD activities in vessels in SHR which supports the hypothesis that there might exist a subtype identified as partial impairment of 11 beta-HSD in patients with essential hypertension. PMID:8331819

  5. Widely Used Pesticides with Previously Unknown Endocrine Activity Revealed as in Vitro Antiandrogens

    PubMed Central

    Orton, Frances; Rosivatz, Erika; Scholze, Martin; Kortenkamp, Andreas

    2011-01-01

    Background Evidence suggests that there is widespread decline in male reproductive health and that antiandrogenic pollutants may play a significant role. There is also a clear disparity between pesticide exposure and data on endocrine disruption, with most of the published literature focused on pesticides that are no longer registered for use in developed countries. Objective We used estimated human exposure data to select pesticides to test for antiandrogenic activity, focusing on highest use pesticides. Methods We used European databases to select 134 candidate pesticides based on highest exposure, followed by a filtering step according to known or predicted receptor-mediated antiandrogenic potency, based on a previously published quantitative structure–activity relationship (QSAR) model. In total, 37 pesticides were tested for in vitro androgen receptor (AR) antagonism. Of these, 14 were previously reported to be AR antagonists (“active”), 4 were predicted AR antagonists using the QSAR, 6 were predicted to not be AR antagonists (“inactive”), and 13 had unknown activity, which were “out of domain” and therefore could not be classified with the QSAR (“unknown”). Results All 14 pesticides with previous evidence of AR antagonism were confirmed as antiandrogenic in our assay, and 9 previously untested pesticides were identified as antiandrogenic (dimethomorph, fenhexamid, quinoxyfen, cyprodinil, λ-cyhalothrin, pyrimethanil, fludioxonil, azinphos-methyl, pirimiphos-methyl). In addition, we classified 7 compounds as androgenic. Conclusions Due to estimated antiandrogenic potency, current use, estimated exposure, and lack of previous data, we strongly recommend that dimethomorph, fludioxonil, fenhexamid, imazalil, ortho-phenylphenol, and pirimiphos-methyl be tested for antiandrogenic effects in vivo. The lack of human biomonitoring data for environmentally relevant pesticides presents a barrier to current risk assessment of pesticides on humans. PMID

  6. Adsorption of selected endocrine disrupting compounds and pharmaceuticals on activated biochars.

    PubMed

    Jung, Chanil; Park, Junyeong; Lim, Kwang Hun; Park, Sunkyu; Heo, Jiyong; Her, Namguk; Oh, Jeill; Yun, Soyoung; Yoon, Yeomin

    2013-12-15

    Chemically activated biochar produced under oxygenated (O-biochar) and oxygen-free (N-biochar) conditions were characterized and the adsorption of endocrine disrupting compounds (EDCs): bisphenol A (BPA), atrazine (ATR), 17 α-ethinylestradiol (EE2), and pharmaceutical active compounds (PhACs); sulfamethoxazole (SMX), carbamazepine (CBM), diclofenac (DCF), ibuprofen (IBP) on both biochars and commercialized powdered activated carbon (PAC) were investigated. Characteristic analysis of adsorbents by solid-state nuclear magnetic resonance (NMR) was conducted to determine better understanding about the EDCs/PhACs adsorption. N-biochar consisted of higher polarity moieties with more alkyl (0-45 ppm), methoxyl (45-63 ppm), O-alkyl (63-108 ppm), and carboxyl carbon (165-187 ppm) content than other adsorbents, while aromaticity of O-biochar was higher than that of N-biochar. O-biochar was composed mostly of aromatic moieties, with low H/C and O/C ratios compared to the highly polarized N-biochar that contained diverse polar functional groups. The higher surface area and pore volume of N-biochar resulted in higher adsorption capacity toward EDCs/PhACs along with atomic-level molecular structural property than O-biochar and PAC. N-biochar had a highest adsorption capacity of all chemicals, suggesting that N-biochar derived from loblolly pine chip is a promising sorbent for agricultural and environmental applications. The adsorption of pH-sensitive dissociable SMX, DCF, IBP, and BPA varied and the order of adsorption capacity was correlated with the hydrophobicity (Kow) of adsorbates throughout the all adsorbents, whereas adsorption of non-ionizable CBM, ATR, and EE2 in varied pH allowed adsorbents to interact with hydrophobic property of adsorbates steadily throughout the study. PMID:24231319

  7. Endocrine Diseases

    MedlinePlus

    ... high or too low, you may have an endocrine disease or disorder. Endocrine diseases and disorders also occur if your body does not respond to hormones the way it is supposed to. Featured Topics Adrenal Insufficiency ... Topics Research Discoveries & News Children with Cushing ...

  8. Purinergic signaling pathways in endocrine system.

    PubMed

    Bjelobaba, Ivana; Janjic, Marija M; Stojilkovic, Stanko S

    2015-09-01

    Adenosine-5'-triphosphate is released by neuroendocrine, endocrine, and other cell types and acts as an extracellular agonist for ligand-gated P2X cationic channels and G protein-coupled P2Y receptors in numerous organs and tissues, including the endocrine system. The breakdown of ATP by ectonucleotidases not only terminates its extracellular messenger functions, but also provides a pathway for the generation of two additional agonists: adenosine 5'-diphosphate, acting via some P2Y receptors, and adenosine, a native agonist for G protein-coupled adenosine receptors, also expressed in the endocrine system. This article provides a review of purinergic signaling pathways in the hypothalamic magnocellular neurosecretory cells and neurohypophysis, hypothalamic parvocellular neuroendocrine system, adenohypophysis, and effector glands organized in five axes: hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid, hypothalamic-pituitary-adrenal, hypothalamic-pituitary-growth hormone, and hypothalamic-pituitary-prolactin. We attempted to summarize current knowledge of purinergic receptor subtypes expressed in the endocrine system, including their roles in intracellular signaling, hormone secretion, and other cell functions. We also briefly review the release mechanism for adenosine-5'-triphosphate by neuroendocrine, endocrine and surrounding cells, the enzymes involved in adenosine-5'-triphosphate hydrolysis to adenosine-5'-diphosphate and adenosine, and the relevance of this pathway for sequential activation of receptors and termination of signaling.

  9. Purinergic Signaling Pathways in Endocrine System

    PubMed Central

    Bjelobaba, Ivana; Janjic, Marija M.; Stojilkovic, Stanko S.

    2015-01-01

    Adenosine-5′-triphosphate is released by neuroendocrine, endocrine, and other cell types and acts as an extracellular agonist for ligand-gated P2X cationic channels and G protein-coupled P2Y receptors in numerous organs and tissues, including the endocrine system. The breakdown of ATP by ectonucleotidases not only terminates its extracellular messenger functions, but also provides a pathway for the generation of two additional agonists: adenosine 5′-diphosphate, acting via some P2Y receptors, and adenosine, a native agonist for G protein-coupled adenosine receptors, also expressed in the endocrine system. This article provides a review of purinergic signaling pathways in the hypothalamic magnocellular neurosecretory cells and neurohypophysis, hypothalamic parvocellular neuroendocrine system, adenohypophysis, and effector glands organized in five axes: hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid, hypothalamic-pituitary-adrenal, hypothalamic-pituitary-growth hormone, and hypothalamic-pituitary-prolactin. We attempted to summarize current knowledge of purinergic receptor subtypes expressed in the endocrine system, including their roles in intracellular signaling, hormone secretion, and other cell functions. We also briefly review the release mechanism for adenosine-5′-triphosphate by neuroendocrine, endocrine and surrounding cells, the enzymes involved in adenosine-5′-triphosphate hydrolysis to adenosine-5′-diphosphate and adenosine, and the relevance of this pathway for sequential activation of receptors and termination of signaling. PMID:25960051

  10. STATUS OF ENDOCRINE DISRUPTOR SCREENING AND TESTING ACTIVITIES IN THE US: IMPLEMENTATION OF THE EDSTAC RECOMMENDATIONS

    EPA Science Inventory

    The last two decades have witnessed a growing concern for chemicals that have the potential to adversely affect the normal functioning of the endocrine system. In 1996, the US Congress passed the Food Quality Protection Act (FQPA) that mandated the US Environmental Protection Ag...

  11. PROTEOMICS IN ECOTOXICOLOGY: PROTEIN EXPRESSION PROFILING TO SCREEN CHEMICALS FOR ENDOCRINE ACTIVITY

    EPA Science Inventory

    Abstract for poster.

    Current endocrine testing methods are animal intensive and lack the throughput necessary to screen large numbers of environmental chemicals for adverse effects. In this study, Matrix Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry...

  12. The removal of endocrine disrupting compounds, pharmaceutically activated compounds and cyanobacterial toxins during drinking water preparation using activated carbon--a review.

    PubMed

    Delgado, Luis F; Charles, Philippe; Glucina, Karl; Morlay, Catherine

    2012-10-01

    This paper provides a review of recent scientific research on the removal by activated carbon (AC) in drinking water (DW) treatment of 1) two classes of currently unregulated trace level contaminants with potential chronic toxicity-pharmaceutically activate compounds (PhACs) and endocrine disrupting compounds (EDCs); 2) cyanobacterial toxins (CyBTs), which are a group of highly toxic and regulated compounds (as microcystin-LR); and 3) the above mentioned compounds by the hybrid system powdered AC/membrane filtration. The influence of solute and AC properties, as well as the competitive effect from background natural organic matter on the adsorption of such trace contaminants, are also considered. In addition, a number of adsorption isotherm parameters reported for PhACs, EDCs and CyBTs are presented herein. AC adsorption has proven to be an effective removal process for such trace contaminants without generating transformation products. This process appears to be a crucial step in order to minimize PhACs, EDCs and CyBTs in finished DW, hence calling for further studies on AC adsorption removal of these compounds. Finally, a priority chart of PhACs and EDCs warranting further study for the removal by AC adsorption is proposed based on the compounds' structural characteristics and their low removal by AC compared to the other compounds.

  13. The removal of endocrine disrupting compounds, pharmaceutically activated compounds and cyanobacterial toxins during drinking water preparation using activated carbon--a review.

    PubMed

    Delgado, Luis F; Charles, Philippe; Glucina, Karl; Morlay, Catherine

    2012-10-01

    This paper provides a review of recent scientific research on the removal by activated carbon (AC) in drinking water (DW) treatment of 1) two classes of currently unregulated trace level contaminants with potential chronic toxicity-pharmaceutically activate compounds (PhACs) and endocrine disrupting compounds (EDCs); 2) cyanobacterial toxins (CyBTs), which are a group of highly toxic and regulated compounds (as microcystin-LR); and 3) the above mentioned compounds by the hybrid system powdered AC/membrane filtration. The influence of solute and AC properties, as well as the competitive effect from background natural organic matter on the adsorption of such trace contaminants, are also considered. In addition, a number of adsorption isotherm parameters reported for PhACs, EDCs and CyBTs are presented herein. AC adsorption has proven to be an effective removal process for such trace contaminants without generating transformation products. This process appears to be a crucial step in order to minimize PhACs, EDCs and CyBTs in finished DW, hence calling for further studies on AC adsorption removal of these compounds. Finally, a priority chart of PhACs and EDCs warranting further study for the removal by AC adsorption is proposed based on the compounds' structural characteristics and their low removal by AC compared to the other compounds. PMID:22885596

  14. Endocrine Diseases

    MedlinePlus

    ... low, you may have a hormone disorder. Hormone diseases also occur if your body does not respond ... In the United States, the most common endocrine disease is diabetes. There are many others. They are ...

  15. INCREASED ENDOCRINE ACTIVITY OF XENOBIOTIC CHEMICALS AS MEDIATED BY METABOLIC ACTIVATION

    EPA Science Inventory

    This research is part of an effort to develop in vitro assays and QSARs applicable to untested chemicals on EPA inventories through study of estrogen receptor (ER) binding and estrogen mediated gene expression in fish. The current effort investigates metabolic activation of chemi...

  16. Method of identification and isolation of organs of endocrine secretion in mice

    SciTech Connect

    Kashirina, N.K.

    1987-10-01

    The authors describe a procedure based on electron autoradiography for isolating and determining the morphology of the adrenal, pituitary, and thyroid glands in albino mice, and use the procedure to give a description, in this paper, of the configuration, location, and physiological interaction of these glands relative to the other organs in these laboratory animals. The procedure overcomes the difficulties encountered in such determinations owing to factors such as smallness.

  17. Circumventricular organs: definition and role in the regulation of endocrine and autonomic function.

    PubMed

    Ganong, W F

    2000-01-01

    1. The circumventricular organs (CVO) are structures that permit polypeptide hypothalamic hormones to leave the brain without disrupting the blood-brain barrier (BBB) and permit substances that do not cross the BBB to trigger changes in brain function. 2. In mammals, CVO include only the median eminence and adjacent neurohypophysis, organum vasculosum lamina terminalis, subfornical organ and the area postrema. 3. The CVO are characterized by their small size, high permeability and fenestrated capillaries. The subcommissural organ is not highly permeable and does not have fenestrated capillaries, but new evidence indicates that it may be involved in the hypertension produced by aldosterone acting on the brain. 4. Feedback control of corticotropin-releasing hormone (CRH) secretion is exerted by free steroids diffusing into the brain, but substances such as cytokines and angiotensin II act on CVO to produce increases in CRH secretion. Gonadal steroids also diffuse into the brain to regulate gonadotrophin-releasing hormone secretion. Thyrotropin-releasing hormone secretion is regulated by thyroid hormones transported across cerebral capillaries. However, CVO may be involved in the negative feedback control of growth hormone and prolactin secretion.

  18. Microchimerism in endocrine pathology.

    PubMed

    Rust, Daniel W; Bianchi, Diana W

    2009-01-01

    Chimerism in an individual refers to the coexistence of cells arising from two distinct organisms. It can arise iatrogenically via transplant or blood transfusion, and physiologically via twin to twin transfer, or from trafficking between mother and fetus during pregnancy. Many of the diseases associated with microchimerism affect the endocrine system (e.g., autoimmune thyroid disease and diabetes mellitus type 1). Microchimerism is relevant to endocrine pathology because (a) it is associated with pregnancy, a condition of complex endocrine physiology; (b) materno-fetal and feto-maternal cellular migration must involve the placenta, itself an endocrine organ; and (c) in some species, chimerism results in states of intersexuality, a condition intimately involved with endocrine physiology. Studies of feto-maternal microchimerism in the thyroid have documented the presence of fetal cells in association with Hashimoto thyroiditis, Graves' disease, thyroid adenoma, and papillary thyroid carcinoma. Studies of materno-fetal microchimerism have documented the presence of maternal cells in juvenile diabetes and other pediatric conditions. Microchimerism plays a potential role in the repair of diseased thyroid and pancreatic tissues.

  19. Screening of endocrine disruption activity in sediments from the Uruguay River.

    PubMed

    Rivas-Rivera, Noelia; Eguren, Gabriela; Carrasco-Letelier, Leonidas; Munkittrick, Kelly R

    2014-08-01

    Sediment constitutes an important sink of endocrine disruptor compounds; however, the potential of sediments to act as a source of endocrine disruptors should be more extensively investigated. The main objective of this study was to determine whether exposure of immature common carp to Uruguay River sediments undergo physiological and endocrine alterations. The lower Uruguay River watershed supports intensive agricultural and forest production, receives municipal sewage discharge and industrial effluent, and a new large pulp mill was constructed in 2006. A 30-day semi-static assay was performed using sediments from four sites along the Uruguay River and compared with an unexposed group in dechlorinated water as a negative control. We focused on two upstream and two downstream sites of a new elemental chlorine free pulp mill. The results showed that plasma vitellogenin levels increased in fish along the river and significant differences were found between the exposed and unexposed groups. Condition factor and gonadosomatic index were not different; however, a significant difference in hepatosomatic index was observed in fish exposed to sediment from an industrial site. A significant reduction in primary spermatocyte accumulation was observed in the exposed group compared with that in the control group, and some individuals exposed to sediments from industrial sites presented with testis-ova. Our results suggest that Uruguay River sediments act as an important source of estrogenic compounds that could be responsible for the alterations observed. Future studies are needed to identify the causal agents and determine exposure routes.

  20. Activation of PI3K/Akt/mTOR signaling in the tumor stroma drives endocrine therapy-dependent breast tumor regression

    PubMed Central

    Polo, María Laura; Riggio, Marina; May, María; Rodríguez, María Jimena; Perrone, María Cecilia; Stallings-Mann, Melody; Kaen, Diego; Frost, Marlene; Goetz, Matthew; Boughey, Judy; Lanari, Claudia; Radisky, Derek; Novaro, Virginia

    2015-01-01

    Improved efficacy of neoadjuvant endocrine-targeting therapies in luminal breast carcinomas could be achieved with optimal use of pathway targeting agents. In a mouse model of ductal breast carcinoma we identify a tumor regressive stromal reaction that is induced by neoadjuvant endocrine therapy. This reparative reaction is characterized by tumor neovascularization accompanied by infiltration of immune cells and carcinoma-associated fibroblasts that stain for phosphorylated ribosomal protein S6 (pS6), downstream the PI3K/Akt/mTOR pathway. While tumor variants with higher PI3K/Akt/mTOR activity respond well to a combination of endocrine and PI3K/Akt/mTOR inhibitors, tumor variants with lower PI3K/Akt/mTOR activity respond more poorly to the combination therapy than to the endocrine therapy alone, associated with inhibition of stromal pS6 and the reparative reaction. In human breast cancer xenografts we confirm that such differential sensitivity to therapy is primarily determined by the level of PI3K/Akt/mTOR in tumor cells. We further show that the clinical response of breast cancer patients undergoing neoadjuvant endocrine therapy is associated with the reparative stromal reaction. We conclude that tumor level and localization of pS6 are associated with therapeutic response in breast cancer and represent biomarkers to distinguish which tumors will benefit from the incorporation of PI3K/Akt/mTOR inhibitors with neoadjuvant endocrine therapy. PMID:26098779

  1. Performance of calcium peroxide for removal of endocrine-disrupting compounds in waste activated sludge and promotion of sludge solubilization.

    PubMed

    Zhang, Ai; Wang, Jie; Li, Yongmei

    2015-03-15

    Removal of six phenolic endocrine disrupting compounds (EDCs) (estrone, 17β-estradiol, 17α-ethinylestradiol, estriol, bisphenol A, and 4-nonylphenols) from waste activated sludge (WAS) was investigated using calcium peroxide (CaO2) oxidation. Effects of initial pH and CaO2 dosage were investigated. The impacts of CaO2 treatment on sludge solubilization and anaerobic digestion were also evaluated. Specifically, the role of reactive oxygen species (ROS) in EDC degradation during CaO2 oxidation was tested. Effects of 6 metal ions contained in the sludge matrix on EDC degradation were also evaluated. The results showed that CaO2 treatment can be a promising technology for EDC removal and facilitating sludge reuse. The EDC removal efficiencies increased with the increase in CaO2 dosage. At CaO2 doses of more than 0.34 g per gram of total solid (g g(-1) TS), more than 50% of EDCs were removed in a wide pH range of 2-12. Higher removal efficiencies were achieved at initial pH values of 12 and 2. The products of EDCs during CaO2 oxidation had less estrogenic activity than the originals. Under the conditions of neutral pH and CaO2 dosage = 0.34 g g(-1) TS, the sludge solubilization can be improved by increasing the soluble total organic carbon (STOC) and volatile suspended solids (VSS) reduction by 25% and 27% in 7 d, respectively; the volatile fatty acid (VFA) production was enhanced by 96% in the 15 d following anaerobic digestion. The ROS released by CaO2 are the main factors contributing to EDC removal, among which, hydroxyl radicals (OH) play the most important role. Metal ions contained in the sludge matrix also affected EDC removal. For most cases, Fe, Cu, and Zn had positive effects; Mn and Ag had negative effects; and Mg had an insignificant effect on EDC removal. PMID:25613412

  2. Notch signaling differentially regulates the cell fate of early endocrine precursor cells and their maturing descendants in the mouse pancreas and intestine.

    PubMed

    Li, Hui Joyce; Kapoor, Archana; Giel-Moloney, Maryann; Rindi, Guido; Leiter, Andrew B

    2012-11-15

    Notch signaling inhibits differentiation of endocrine cells in the pancreas and intestine. In a number of cases, the observed inhibition occurred with Notch activation in multipotential cells, prior to the initiation of endocrine differentiation. It has not been established how direct activation of Notch in endocrine precursor cells affects their subsequent cell fate. Using conditional activation of Notch in cells expressing Neurogenin3 or NeuroD1, we examined the effects of Notch in both organs, on cell fate of early endocrine precursors and maturing endocrine-restricted cells, respectively. Notch did not preclude the differentiation of a limited number of endocrine cells in either organ when activated in Ngn3(+) precursor cells. In addition, in the pancreas most Ngn3(+) cells adopted a duct but not acinar cell fate; whereas in intestinal Ngn3(+) cells, Notch favored enterocyte and goblet cell fates, while selecting against endocrine and Paneth cell differentiation. A small fraction of NeuroD1(+) cells in the pancreas retain plasticity to respond to Notch, giving rise to intraislet ductules as well as cells with no detectable pancreatic lineage markers that appear to have limited ultrastructural features of both endocrine and duct cells. These results suggest that Notch directly regulates cell fate decisions in multipotential early endocrine precursor cells. Some maturing endocrine-restricted NeuroD1(+) cells in the pancreas switch to the duct lineage in response to Notch, indicating previously unappreciated plasticity at such a late stage of endocrine differentiation.

  3. Occurrence of Endocrine Active Compounds and Biological Responses in the Mississippi River - Study Design and Data, June through August 2006

    USGS Publications Warehouse

    Lee, Kathy E.; Yaeger, Christine S.; Jahns, Nathan D.; Schoenfuss, Heiko L.

    2008-01-01

    Concern that selected chemicals in the environment may act as endocrine active compounds in aquatic ecosystems is widespread; however, few studies have examined the occurrence of endocrine active compounds and identified biological markers of endocrine disruption such as intersex occurrence in fish longitudinally in a river system. This report presents environmental data collected and analyzed by the U.S. Geological Survey, Minnesota Pollution Control Agency and St. Cloud State University as part of an integrated biological and chemical study of endocrine disruption in fish in the Mississippi River. Data were collected from water, bed sediment, and fish at 43 sites along the river from the headwaters at Lake Itasca to 14 miles downstream from Brownsville, Minnesota during June through August 2006. Twenty-four individual compounds were detected in water samples, with cholesterol, atrazine, N,N-diethyl-meta-toluamide, metolachlor, and hexahydrohexamethylcyclopentabenzopyran detected most frequently (in at least 10 percent of the samples). The number of compounds detected in water per site ranged from 0 to 8. Forty individual compounds were detected in bed-sediment samples. The most commonly detected compounds (in at least 50 percent of the samples) were indole, beta-sitosterol, cholesterol, beta-stigmastanol, 3-methyl-1H-indole, p-cresol, pyrene, phenol, fluoranthene, 3-beta coprostanol, benzo[a]pyrene, acetophenone, and 2,6-dimethylnaphthalene. The total number of detections in bed sediment (at a site) ranged from 3 to 31. The compounds NP1EO, NP2EO, and 4-nonylphenol were detected in greater than 10 percent of the samples. Most (80 percent) female fish collected had measurable concentrations of vitellogenin. Vitellogenin also was detected in 62, 63, and 33 percent of male carp, smallmouth bass, and redhorse, respectively. The one male walleye sample plasma sample analyzed had a vitellogenin detection. Vitellogenin concentrations were lower in male fish (not

  4. Thyroid endocrine status of wild European eels (Anguilla anguilla) in the Loire (France). Relationships with organic contaminant body burdens.

    PubMed

    Couderc, M; Marchand, J; Zalouk-Vergnoux, A; Kamari, A; Moreau, B; Blanchet-Letrouvé, I; Le Bizec, B; Mouneyrac, C; Poirier, L

    2016-04-15

    In teleost fish, thyroid function is involved in various critical physiological processes. Given the complexity of the hypothalamo-pituitary-thyroid (HPT) axis, a large number of genes and proteins can be the potential target of endocrine-disrupting compounds (EDCs). The aim of this study was to evaluate, in yellow and silver European eels (Anguilla anguilla), potential effects of EDCs on thyroid status by analyzing the associations between EDC body burdens and thyroid hormones (THs). In yellow individuals, greater free T3/T4 ratios (FT3/FT4) and lower plasma FT4 levels were associated with greater concentrations of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs), as highlighted by significant correlations with many congeners. Few positive relationships with alkylphenols were noticed. In contrast, silver eels usually exhibited less significant correlations between THs and contaminant loads. Expression of a series of genes involved in the HPT axis was also investigated in the silver individuals. Concerning mRNA expression in silver females, some main correlations were noticed: thyroid-stimulating hormone (TSHβ) gene expression was significantly correlated to numerous PCBs, and hepatic mRNA levels of deiodinase 2 (Deio 2) were negatively correlated to 2-hydroxyfluorene (2-OHF) and 2-naphtol (2-OHNa). Thyroid receptor (TRα and TRβ) mRNA levels exhibited weak negative correlations with some PBDEs in silver females and males. Hepatic vitellogenin (Vtg) mRNA levels were detected in all silver males but at lower levels than in silver females. In males, Vtg mRNA levels were positively associated to FT4/TT4. In silver females, strong positive correlations were found between congeners of PCBs, PBDEs and PFAS suggesting potential estrogenic effects. Overall, the observed results indicate that several organic contaminants, mainly dl-, ndl-PCBs and PBDEs, could be associated with changes in thyroid homeostasis in these fish, via direct or indirect

  5. Endocrine effects of real-life mixtures of persistent organic pollutants (POP) in experimental models and wild fish.

    PubMed

    Berg, Vidar; Kraugerud, Marianne; Nourizadeh-Lillabadi, Rasoul; Olsvik, Pål A; Skåre, Janneche U; Alestrøm, Peter; Ropstad, Erik; Zimmer, Karin Elisabeth; Lyche, Jan L

    2016-01-01

    A series of studies have assessed the occurrence, levels, and potential adverse effects of persistent organic pollutants (POP) in fish from Lake Mjøsa. In this lake, high levels of various POP were detected in biota. Fish from the nearby Lake Losna contain background levels of POP and served as reference (controls) in these studies. Significantly higher prevalence of mycobacteriosis and pathological changes were documented in burbot (Lota lota) from Mjøsa compared to burbot from Losna. Further, transcriptional profiling identified changes in gene expression in burbot from Mjøsa compared to burbot from Losna associated with drug metabolism enzymes and oxidative stress. POP extracted from burbot liver oil from the two lakes was used to expose zebrafish (Danio rerio) during two consecutive generations. During both generations, POP mixtures from both lakes increased the rate of mortality, induced earlier onset of puberty, and skewed sex ratio toward males. However, opposite effects on weight gain were found in exposure groups compared to controls during the two generations. Exposure to POP from both lakes was associated with suppression of ovarian follicle development. Analyses of genome-wide transcription profiling identified functional networks of genes associated with weight homeostasis, steroid hormone functions, and insulin signaling. In human cell studies using adrenocortical H295R and primary porcine theca and granulosa cells, exposure to lake extracts from both populations modulated steroid hormone production with significant difference from controls. The results suggest that POP from both lakes may possess the potential to induce endocrine disruption and may adversely affect health in wild fish. PMID:27484136

  6. Effects of Age, Sex and Multiple Endocrine Neoplasia Type-II on Silver Stained Nucleolar Organizer Regions

    PubMed Central

    Butler, Merlin G.; Lane, John R.

    2016-01-01

    Summary Silver stained nucleolar organizer regions (AgNORs) were studied in phytohemagglutinin (PHA)-stimulated lymphocytes from 55 Caucasian control individuals (34 females with average age of 24 years and age range 19 weeks gestation to 87 years; 21 males with average age of 31 years and age range 29 weeks gestation to 72 years) and 13 individuals (7 females, 6 males; average age 38.8 years with age range 25—58 years) with multiple endocrine neoplasia-type II (MEN-II), an autosomal dominant malignancy with increased chromosome breakage. For the first time, AgNORs were examined in lymphocytes from normal fetuses and patients with MEN-II in order to determine the effects of age, sex or malignancy on the number of AgNORs. No significant difference in the average number of AgNORs were found in fetal cells (8.2 ± S.D. 0.7/cell) when compared with cells from older individuals including those over 65 years of age (8.0 ± S.D. 0.8/cell). There was a statistically significant negative correlation (P< 0.05) between the modal number of AgNORs on G but not D chromosomes in both males and females. A negative correlation was also found between the mean number of AgNORs and age but was not statistically significant. The average number of AgNORs in the MEN-II individuals was 8.5 ± S.D. 0.7/cell, which was not significantly different than 8.2 ± S.D. 0.7/cell observed in age-matched control subjects. PMID:2471022

  7. Alkylphenols, Other Endocrine-Active Chemicals, and Fish Responses in Three Streams in Minnesota - Study Design and Data, February-September 2007

    USGS Publications Warehouse

    Lee, Kathy E.; Schoenfuss, Heiko L.; Jahns, Nathan D.; Brown, Greg K.; Barber, Larry B.

    2008-01-01

    This report presents the study design and environmental data for an integrated chemical and biological study of three streams (South Fork Crow River, Redwood River, and Grindstone River) that receive wastewater in Minnesota. The objective of the study was to identify distribution patterns of endocrine-active chemicals and other organic chemicals indicative of wastewater, and to identify fish responses in the same streams. Endocrine-active chemicals are a class of chemicals that interfere with the natural regulation of endocrine systems, and an understanding of their distribution in aquatic systems is important so that aquatic organism exposure can be evaluated. This study was a cooperative effort of the U.S. Geological Survey (USGS), the Minnesota Pollution Control Agency, and St. Cloud State University (St. Cloud, Minn.). The USGS collected and analyzed water and quality-assurance samples and measured streamflow during six sampling events in each of three streams. Water samples were collected upstream from and at two successive points downstream from wastewater-treatment plant (WWTP) effluent discharge and from treated effluent from February through September 2007. Bed-sediment samples were collected during one sampling period at each of the stream locations. Water and bed-sediment samples were analyzed for endocrine-active chemicals including alkylphenols, alkylphenol polyethoxylates, and nonylphenol ethoxycarboxlylates (NPECs). Water samples also were analyzed for major ions, nutrients, and organic carbon. In addition, as part of an intensive time-series investigation, the USGS staff collected daily water samples for 8 weeks from the Redwood River near Marshall, Minn., for analyses of total alkylphenols and atrazine. St. Cloud State University staff collected and analyzed fish to determine male fish responses at all water sampling sites and at an additional site near the discharge of wastewater-treatment plant effluent to these streams. Male fish responses

  8. Targeting chromatin binding regulation of constitutively active AR variants to overcome prostate cancer resistance to endocrine-based therapies

    PubMed Central

    Chan, Siu Chiu; Selth, Luke A.; Li, Yingming; Nyquist, Michael D.; Miao, Lu; Bradner, James E.; Raj, Ganesh V.; Tilley, Wayne D.; Dehm, Scott M.

    2015-01-01

    Androgen receptor (AR) variants (AR-Vs) expressed in prostate cancer (PCa) lack the AR ligand binding domain (LBD) and function as constitutively active transcription factors. AR-V expression in patient tissues or circulating tumor cells is associated with resistance to AR-targeting endocrine therapies and poor outcomes. Here, we investigated the mechanisms governing chromatin binding of AR-Vs with the goal of identifying therapeutic vulnerabilities. By chromatin immunoprecipitation and sequencing (ChIP-seq) and complementary biochemical experiments, we show that AR-Vs display a binding preference for the same canonical high-affinity androgen response elements (AREs) that are preferentially engaged by AR, albeit with lower affinity. Dimerization was an absolute requirement for constitutive AR-V DNA binding and transcriptional activation. Treatment with the bromodomain and extraterminal (BET) inhibitor JQ1 resulted in inhibition of AR-V chromatin binding and impaired AR-V driven PCa cell growth in vitro and in vivo. Importantly, this was associated with a novel JQ1 action of down-regulating AR-V transcript and protein expression. Overall, this study demonstrates that AR-Vs broadly restore AR chromatin binding events that are otherwise suppressed during endocrine therapy, and provides pre-clinical rationale for BET inhibition as a strategy for inhibiting expression and chromatin binding of AR-Vs in PCa. PMID:25908785

  9. Reprogramming metabolism by histone methyltransferase NSD2 drives endocrine resistance via coordinated activation of pentose phosphate pathway enzymes.

    PubMed

    Wang, Junjian; Duan, Zhijian; Nugent, Zoann; Zou, June X; Borowsky, Alexander D; Zhang, Yanhong; Tepper, Clifford G; Li, Jian Jian; Fiehn, Oliver; Xu, Jianzhen; Kung, Hsing-Jien; Murphy, Leigh C; Chen, Hong-Wu

    2016-08-10

    Metabolic reprogramming such as the aerobic glycolysis or Warburg effect is well recognized as a common feature of tumorigenesis. However, molecular mechanisms underlying metabolic alterations for tumor therapeutic resistance are poorly understood. Through gene expression profiling analysis we found that histone H3K36 methyltransferase NSD2/MMSET/WHSC1 expression was highly elevated in tamoxifen-resistant breast cancer cell lines and clinical tumors. IHC analysis indicated that NSD2 protein overexpression was associated with the disease recurrence and poor survival. Ectopic expression of NSD2 wild type, but not the methylase-defective mutant, drove endocrine resistance in multiple cell models and xenograft tumors. Mechanistically, NSD2 was recruited to and methylated H3K36me2 at the promoters of key glucose metabolic enzyme genes. Its overexpression coordinately up-regulated hexokinase 2 (HK2) and glucose-6-phosphate dehydrogenase (G6PD), two key enzymes of glycolysis and the pentose phosphate pathway (PPP), as well as TP53-induced glycolysis regulatory phosphatase TIGAR. Consequently, NSD2-driven tamoxifen-resistant cells and tumors displayed heightened PPP activity, elevated NADPH production, and reduced ROS level, without significantly altered glycolysis. These results illustrate a coordinated, epigenetic activation of key glucose metabolic enzymes in therapeutic resistance and nominate methyltransferase NSD2 as a potential therapeutic target for endocrine resistant breast cancer.

  10. Targeting chromatin binding regulation of constitutively active AR variants to overcome prostate cancer resistance to endocrine-based therapies.

    PubMed

    Chan, Siu Chiu; Selth, Luke A; Li, Yingming; Nyquist, Michael D; Miao, Lu; Bradner, James E; Raj, Ganesh V; Tilley, Wayne D; Dehm, Scott M

    2015-07-13

    Androgen receptor (AR) variants (AR-Vs) expressed in prostate cancer (PCa) lack the AR ligand binding domain (LBD) and function as constitutively active transcription factors. AR-V expression in patient tissues or circulating tumor cells is associated with resistance to AR-targeting endocrine therapies and poor outcomes. Here, we investigated the mechanisms governing chromatin binding of AR-Vs with the goal of identifying therapeutic vulnerabilities. By chromatin immunoprecipitation and sequencing (ChIP-seq) and complementary biochemical experiments, we show that AR-Vs display a binding preference for the same canonical high-affinity androgen response elements (AREs) that are preferentially engaged by AR, albeit with lower affinity. Dimerization was an absolute requirement for constitutive AR-V DNA binding and transcriptional activation. Treatment with the bromodomain and extraterminal (BET) inhibitor JQ1 resulted in inhibition of AR-V chromatin binding and impaired AR-V driven PCa cell growth in vitro and in vivo. Importantly, this was associated with a novel JQ1 action of down-regulating AR-V transcript and protein expression. Overall, this study demonstrates that AR-Vs broadly restore AR chromatin binding events that are otherwise suppressed during endocrine therapy, and provides pre-clinical rationale for BET inhibition as a strategy for inhibiting expression and chromatin binding of AR-Vs in PCa.

  11. Changes in endocrine profile and reproductive organs during puberty in the male marmoset monkey (Callithrix jacchus).

    PubMed

    Chandolia, Ramesh K; Luetjens, Craig Marc; Wistuba, Joachim; Yeung, Ching-Hei; Nieschlag, Eberhard; Simoni, Manuela

    2006-08-01

    Data on pubertal maturation in male marmoset, a model for human reproduction, are scant and conflicting. We collected data on novel parameters to characterize puberty. Twenty-five marmoset monkeys were assigned to five age groups by weeks (wk): 21 (pre-pubertal), 43 (onset of puberty), 52 (fully pubertal), 70 (mature), and 116 (fully adult). Serum and intratesticular testosterone and pituitary bioactive chorionic gonadotropin (bioCG) were measured. Testicular development was assessed by ultrasonography, histology, and flow cytometry. Three consecutive blood samples revealed extreme fluctuations in testosterone concentrations, suggesting an erratic secretion. Age-related changes in serum testosterone and pituitary bioCG concentrations were observed. Intratesticular androgens (ITAs) showed high fluctuations within groups at all ages and were high in some animals by 21 wk. Unexpectedly, no correlation between pituitary bioCG and serum testosterone or ITAs was found, but these parameters significantly correlated with testicular weight and volume. These observations were consistent a dependence on the testis growth on bioCG. Unfortunately, the low serum levels of bioCG were not measurable in this study. At 43 wk, the animals reached puberty. At 52 wk of age, animals attained maximum body and epididymal weights and qualitatively normal spermatogenesis, but testes continued growing, reaching a maximum of all parameters at 70 wk of age, without further major changes at the age of 116 wk. It is concluded that (1) gonadal activation is evident at wk 21, (2) the male marmoset reaches the pubertal threshold around 43 wk of age, attains qualitative parameters at 52 wk, matures further to sexual maturity at 70 wk, and (3) serum testosterone and ITAs are highly variable without any identifiable correlation with pituitary bioCG.

  12. Do endocrine disruptors cause hypospadias?

    PubMed Central

    Botta, Sisir; Cunha, Gerald R.

    2014-01-01

    Introduction Endocrine disruptors or environmental agents, disrupt the endocrine system, leading to various adverse effects in humans and animals. Although the phenomenon has been noted historically in the cases of diethylstilbestrol (DES) and dichlorodiphenyltrichloroethane (DDT), the term “endocrine disruptor” is relatively new. Endocrine disruptors can have a variety of hormonal activities such as estrogenicity or anti-androgenicity. The focus of this review concerns on the induction of hypospadias by exogenous estrogenic endocrine disruptors. This has been a particular clinical concern secondary to reported increased incidence of hypospadias. Herein, the recent literature is reviewed as to whether endocrine disruptors cause hypospadias. Methods A literature search was performed for studies involving both humans and animals. Studies within the past 5 years were reviewed and categorized into basic science, clinical science, epidemiologic, or review studies. Results Forty-three scientific articles were identified. Relevant sentinel articles were also reviewed. Additional pertinent studies were extracted from the reference of the articles that obtained from initial search results. Each article was reviewed and results presented. Overall, there were no studies which definitely stated that endocrine disruptors caused hypospadias. However, there were multiple studies which implicated endocrine disruptors as one component of a multifactorial model for hypospadias. Conclusions Endocrine disruption may be one of the many critical steps in aberrant development that manifests as hypospadias. PMID:26816789

  13. 28 CFR 551.34 - Organization activities.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Organization activities. 551.34 Section... MISCELLANEOUS Inmate Organizations § 551.34 Organization activities. (a) An officer of the inmate organization... organization; (2) Nature or purpose of the activity; (3) Date, time, and estimated duration of the activity;...

  14. 28 CFR 551.34 - Organization activities.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Organization activities. 551.34 Section... MISCELLANEOUS Inmate Organizations § 551.34 Organization activities. (a) An officer of the inmate organization... organization; (2) Nature or purpose of the activity; (3) Date, time, and estimated duration of the activity;...

  15. 28 CFR 551.34 - Organization activities.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Organization activities. 551.34 Section... MISCELLANEOUS Inmate Organizations § 551.34 Organization activities. (a) An officer of the inmate organization... organization; (2) Nature or purpose of the activity; (3) Date, time, and estimated duration of the activity;...

  16. 28 CFR 551.34 - Organization activities.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Organization activities. 551.34 Section... MISCELLANEOUS Inmate Organizations § 551.34 Organization activities. (a) An officer of the inmate organization... organization; (2) Nature or purpose of the activity; (3) Date, time, and estimated duration of the activity;...

  17. 28 CFR 551.34 - Organization activities.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Organization activities. 551.34 Section... MISCELLANEOUS Inmate Organizations § 551.34 Organization activities. (a) An officer of the inmate organization... organization; (2) Nature or purpose of the activity; (3) Date, time, and estimated duration of the activity;...

  18. [Dementia due to Endocrine Diseases].

    PubMed

    Matsunaga, Akiko; Yoneda, Makoto

    2016-04-01

    Endocrine diseases affecting various organs, such as the pituitary gland, the thyroid, the parathyroid, the adrenal glands and the pancreas, occasionally cause dementia. While Alzheimer's disease (AD) is the main cause of dementia in the elderly and is untreatable, dementia caused by endocrine diseases is treatable in most cases. However, patients with dementia associated with endocrine diseases show memory impairments similar to those found in AD, often leading to misdiagnoses. Patients with endocrine diseases often present with other characteristic systemic and neuropsychiatric symptoms caused by altered hormone levels. Such neuropsychiatric symptoms include involuntary movements, depression, seizures, and muscle weakness. In these cases, abnormalities in imaging and blood or urine tests are helpful in making a differential diagnosis. As delays in the diagnosis and treatment of these patients may cause irreversible brain damage, it is imperative for clinicians to carefully exclude the possibility of latent endocrine diseases when treating patients with dementia.

  19. The Role of Cholesterol Utilization in a Computational Adrenal Steroidogenesis Model to Improve Predictability of Biochemical Responses to Endocrine Active Chemicals

    EPA Science Inventory

    Steroids, which have an important role in a wide range of physiological processes, are synthesized primarily in the gonads and adrenal glands through a series of enzyme-mediated reactions. The activity of steroidogenic enzymes can be altered by a variety of endocrine active chem...

  20. In vitro characterization of the effectiveness of enhanced sewage treatment processes to eliminate endocrine activity of hospital effluents.

    PubMed

    Maletz, Sibylle; Floehr, Tilman; Beier, Silvio; Klümper, Claudia; Brouwer, Abraham; Behnisch, Peter; Higley, Eric; Giesy, John P; Hecker, Markus; Gebhardt, Wilhelm; Linnemann, Volker; Pinnekamp, Johannes; Hollert, Henner

    2013-03-15

    Occurrence of pharmaceuticals in aquatic ecosystems is related to sewage effluents. Due to the possible adverse effects on wildlife and humans, degradation and removal of pharmaceuticals and their metabolites during wastewater treatment is an increasingly important task. The present study was part of a proof of concept study at a medium sized country hospital in western Germany that investigated efficiency of advanced treatment processes to remove toxic potencies from sewage. Specifically, the efficiency of treatment processes such as a membrane bioreactor (MBR) and ozonation to remove endocrine disruptive potentials was assessed. Estrogenic effects were characterized by use of two receptor-mediated in vitro transactivation assays, the Lyticase Yeast Estrogen Screen (LYES) and the Estrogen Receptor mediated Chemical Activated LUciferase gene eXpression (ER CALUX(®)). In addition, the H295R Steroidogenesis Assay (H295R) was utilized to detect potential disruption of steroidogenesis. Raw sewage contained measurable estrogen receptor (ER)-mediated potency as determined by use of the LYES (28.9 ± 8.6 ng/L, 0.33× concentration), which was reduced after treatment by MBR (2.3 ± 0.3 ng/L) and ozone (1.2 ± 0.4 ng/L). Results were confirmed by use of ER CALUX(®) which measured concentrations of estrogen equivalents (EEQs) of 0.2 ± 0.11 ng/L (MBR) and 0.01 ± 0.02 ng/L (ozonation). In contrast, treatment with ozone resulted in greater production of estradiol and aromatase activity at 3× and greater concentrations in H295R cells. It is hypothesized that this is partly due to formation of active oxidized products during ozonation. Substance-specific analyses demonstrated efficient removal of most of the measured compounds by ozonation. A comparison of the ER-mediated responses measured by use of the LYES and ER CALUX(®) with those from the chemical analysis using a mass-balance approach revealed estrone (E1) to be the main compound that caused the estrogenic effects

  1. The Endocrine Machinery.

    ERIC Educational Resources Information Center

    Fillman, David

    1987-01-01

    Promotes a reductionist approach to teaching about the endocrine system in high school biology and anatomy courses. Encourages the study of how hormones travel to the cells and affect them. Provides suggestions for activities and discussion questions, along with sample diagrams and flow charts. (TW)

  2. Interlaboratory comparison of in vitro bioassays for screening of endocrine active chemicals in recycled water.

    PubMed

    Mehinto, Alvine C; Jia, Ai; Snyder, Shane A; Jayasinghe, B Sumith; Denslow, Nancy D; Crago, Jordan; Schlenk, Daniel; Menzie, Christopher; Westerheide, Sandy D; Leusch, Frederic D L; Maruya, Keith A

    2015-10-15

    In vitro bioassays have shown promise as water quality monitoring tools. In this study, four commercially available in vitro bioassays (GeneBLAzer(®) androgen receptor (AR), estrogen receptor-alpha (ER), glucocorticoid receptor (GR) and progesterone receptor (PR) assays) were adapted to screen for endocrine active chemicals in samples from two recycled water plants. The standardized protocols were used in an interlaboratory comparison exercise to evaluate the reproducibility of in vitro bioassay results. Key performance criteria were successfully achieved, including low background response, standardized calibration parameters and high intra-laboratory precision. Only two datasets were excluded due to poor calibration performance. Good interlaboratory reproducibility was observed for GR bioassay, with 16-26% variability among the laboratories. ER and PR bioactivity was measured near the bioassay limit of detection and showed more variability (21-54%), although interlaboratory agreement remained comparable to that of conventional analytical methods. AR bioassay showed no activity for any of the samples analyzed. Our results indicate that ER, GR and PR, were capable of screening for different water quality, i.e., the highest bioactivity was observed in the plant influent, which also contained the highest concentrations of endocrine active chemicals measured by LC-MS/MS. After advanced treatment (e.g., reverse osmosis), bioactivity and target chemical concentrations were both below limits of detection. Comparison of bioassay and chemical equivalent concentrations revealed that targeted chemicals accounted for ≤5% of bioassay activity, suggesting that detection limits by LC-MS/MS for some chemicals were insufficient and/or other bioactive compounds were present in these samples. Our study demonstrated that in vitro bioassays responses were reproducible, and can provide information to complement conventional analytical methods for a more comprehensive water quality

  3. Interlaboratory comparison of in vitro bioassays for screening of endocrine active chemicals in recycled water.

    PubMed

    Mehinto, Alvine C; Jia, Ai; Snyder, Shane A; Jayasinghe, B Sumith; Denslow, Nancy D; Crago, Jordan; Schlenk, Daniel; Menzie, Christopher; Westerheide, Sandy D; Leusch, Frederic D L; Maruya, Keith A

    2015-10-15

    In vitro bioassays have shown promise as water quality monitoring tools. In this study, four commercially available in vitro bioassays (GeneBLAzer(®) androgen receptor (AR), estrogen receptor-alpha (ER), glucocorticoid receptor (GR) and progesterone receptor (PR) assays) were adapted to screen for endocrine active chemicals in samples from two recycled water plants. The standardized protocols were used in an interlaboratory comparison exercise to evaluate the reproducibility of in vitro bioassay results. Key performance criteria were successfully achieved, including low background response, standardized calibration parameters and high intra-laboratory precision. Only two datasets were excluded due to poor calibration performance. Good interlaboratory reproducibility was observed for GR bioassay, with 16-26% variability among the laboratories. ER and PR bioactivity was measured near the bioassay limit of detection and showed more variability (21-54%), although interlaboratory agreement remained comparable to that of conventional analytical methods. AR bioassay showed no activity for any of the samples analyzed. Our results indicate that ER, GR and PR, were capable of screening for different water quality, i.e., the highest bioactivity was observed in the plant influent, which also contained the highest concentrations of endocrine active chemicals measured by LC-MS/MS. After advanced treatment (e.g., reverse osmosis), bioactivity and target chemical concentrations were both below limits of detection. Comparison of bioassay and chemical equivalent concentrations revealed that targeted chemicals accounted for ≤5% of bioassay activity, suggesting that detection limits by LC-MS/MS for some chemicals were insufficient and/or other bioactive compounds were present in these samples. Our study demonstrated that in vitro bioassays responses were reproducible, and can provide information to complement conventional analytical methods for a more comprehensive water quality

  4. Thyroid endocrine status of wild European eels (Anguilla anguilla) in the Loire (France). Relationships with organic contaminant body burdens.

    PubMed

    Couderc, M; Marchand, J; Zalouk-Vergnoux, A; Kamari, A; Moreau, B; Blanchet-Letrouvé, I; Le Bizec, B; Mouneyrac, C; Poirier, L

    2016-04-15

    In teleost fish, thyroid function is involved in various critical physiological processes. Given the complexity of the hypothalamo-pituitary-thyroid (HPT) axis, a large number of genes and proteins can be the potential target of endocrine-disrupting compounds (EDCs). The aim of this study was to evaluate, in yellow and silver European eels (Anguilla anguilla), potential effects of EDCs on thyroid status by analyzing the associations between EDC body burdens and thyroid hormones (THs). In yellow individuals, greater free T3/T4 ratios (FT3/FT4) and lower plasma FT4 levels were associated with greater concentrations of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs), as highlighted by significant correlations with many congeners. Few positive relationships with alkylphenols were noticed. In contrast, silver eels usually exhibited less significant correlations between THs and contaminant loads. Expression of a series of genes involved in the HPT axis was also investigated in the silver individuals. Concerning mRNA expression in silver females, some main correlations were noticed: thyroid-stimulating hormone (TSHβ) gene expression was significantly correlated to numerous PCBs, and hepatic mRNA levels of deiodinase 2 (Deio 2) were negatively correlated to 2-hydroxyfluorene (2-OHF) and 2-naphtol (2-OHNa). Thyroid receptor (TRα and TRβ) mRNA levels exhibited weak negative correlations with some PBDEs in silver females and males. Hepatic vitellogenin (Vtg) mRNA levels were detected in all silver males but at lower levels than in silver females. In males, Vtg mRNA levels were positively associated to FT4/TT4. In silver females, strong positive correlations were found between congeners of PCBs, PBDEs and PFAS suggesting potential estrogenic effects. Overall, the observed results indicate that several organic contaminants, mainly dl-, ndl-PCBs and PBDEs, could be associated with changes in thyroid homeostasis in these fish, via direct or indirect

  5. The Activation Mechanism of Glycoprotein Hormone Receptors with Implications in the Cause and Therapy of Endocrine Diseases.

    PubMed

    Brüser, Antje; Schulz, Angela; Rothemund, Sven; Ricken, Albert; Calebiro, Davide; Kleinau, Gunnar; Schöneberg, Torsten

    2016-01-01

    Glycoprotein hormones (GPHs) are the main regulators of the pituitary-thyroid and pituitary-gonadal axes. Selective interaction between GPHs and their cognate G protein-coupled receptors ensure specificity in GPH signaling. The mechanisms of how these hormones activate glycoprotein hormone receptors (GPHRs) or how mutations and autoantibodies can alter receptor function were unclear. Based on the hypothesis that GPHRs contain an internal agonist, we systematically screened peptide libraries derived from the ectodomain for agonistic activity on the receptors. We show that a peptide (p10) derived from a conserved sequence in the C-terminal part of the extracellular N terminus can activate all GPHRs in vitro and in GPHR-expressing tissues. Inactivating mutations in this conserved region or in p10 can inhibit activation of the thyroid-stimulating hormone receptor by autoantibodies. Our data suggest an activation mechanism where, upon extracellular ligand binding, this intramolecular agonist isomerizes and induces structural changes in the 7-transmembrane helix domain, triggering G protein activation. This mechanism can explain the pathophysiology of activating autoantibodies and several mutations causing endocrine dysfunctions such as Graves disease and hypo- and hyperthyroidism. Our findings highlight an evolutionarily conserved activation mechanism of GPHRs and will further promote the development of specific ligands useful to treat Graves disease and other dysfunctions of GPHRs.

  6. Mobilization of endocrine-disrupting chemicals and estrogenic activity in simulated rainfall runoff from land-applied biosolids.

    PubMed

    Giudice, Ben D; Young, Thomas M

    2011-10-01

    Municipal biosolids are commonly applied to land as soil amendment or fertilizer as a form of beneficial reuse of what could otherwise be viewed as waste. Balanced against this benefit are potential risks to groundwater and surface water quality from constituents that may be mobilized during storm events. The objective of the present study was to characterize the mobilization of selected endocrine-disrupting compounds, heavy metals, and total estrogenic activity in rainfall runoff from land-applied biosolids. Rainfall simulations were conducted on soil plots amended with biosolids. Surface runoff and leachate was collected and analyzed for the endocrine-disrupting compounds bisphenol A, 17α-ethynylestradiol, triclocarban, triclosan, octylphenol, and nonylphenol; a suite of 16 metals; and estrogenic activity via the estrogen receptor-mediated chemical activated luciferase gene expression (ER-CALUX) bioassay. Triclocarban (2.3-17.3 ng/L), triclosan (<51-309 ng/L), and octylphenol (<4.9-203 ng/L) were commonly detected. Chromium (2.0-22 µg/L), Co (2.5-10 µg/L), Ni (28-235 µg/L), Cu (14-110 µg/L), As (1.2-2.7 µg/L), and Se (0.29-12 µg/L) were quantifiable over background levels. Triclosan, Ni, and Cu were detected at levels that might pose some risk to aquatic life, though levels of metals in the biosolids were well below the maximum allowable regulatory limits. The ER-CALUX results were mostly explained by background bisphenol A contamination and octylphenol in runoff, although unknown contributors or matrix effects were also found. PMID:21786314

  7. Mobilization of endocrine-disrupting chemicals and estrogenic activity in simulated rainfall runoff from land-applied biosolids.

    PubMed

    Giudice, Ben D; Young, Thomas M

    2011-10-01

    Municipal biosolids are commonly applied to land as soil amendment or fertilizer as a form of beneficial reuse of what could otherwise be viewed as waste. Balanced against this benefit are potential risks to groundwater and surface water quality from constituents that may be mobilized during storm events. The objective of the present study was to characterize the mobilization of selected endocrine-disrupting compounds, heavy metals, and total estrogenic activity in rainfall runoff from land-applied biosolids. Rainfall simulations were conducted on soil plots amended with biosolids. Surface runoff and leachate was collected and analyzed for the endocrine-disrupting compounds bisphenol A, 17α-ethynylestradiol, triclocarban, triclosan, octylphenol, and nonylphenol; a suite of 16 metals; and estrogenic activity via the estrogen receptor-mediated chemical activated luciferase gene expression (ER-CALUX) bioassay. Triclocarban (2.3-17.3 ng/L), triclosan (<51-309 ng/L), and octylphenol (<4.9-203 ng/L) were commonly detected. Chromium (2.0-22 µg/L), Co (2.5-10 µg/L), Ni (28-235 µg/L), Cu (14-110 µg/L), As (1.2-2.7 µg/L), and Se (0.29-12 µg/L) were quantifiable over background levels. Triclosan, Ni, and Cu were detected at levels that might pose some risk to aquatic life, though levels of metals in the biosolids were well below the maximum allowable regulatory limits. The ER-CALUX results were mostly explained by background bisphenol A contamination and octylphenol in runoff, although unknown contributors or matrix effects were also found.

  8. Phylogenetic organization of bacterial activity.

    PubMed

    Morrissey, Ember M; Mau, Rebecca L; Schwartz, Egbert; Caporaso, J Gregory; Dijkstra, Paul; van Gestel, Natasja; Koch, Benjamin J; Liu, Cindy M; Hayer, Michaela; McHugh, Theresa A; Marks, Jane C; Price, Lance B; Hungate, Bruce A

    2016-09-01

    Phylogeny is an ecologically meaningful way to classify plants and animals, as closely related taxa frequently have similar ecological characteristics, functional traits and effects on ecosystem processes. For bacteria, however, phylogeny has been argued to be an unreliable indicator of an organism's ecology owing to evolutionary processes more common to microbes such as gene loss and lateral gene transfer, as well as convergent evolution. Here we use advanced stable isotope probing with (13)C and (18)O to show that evolutionary history has ecological significance for in situ bacterial activity. Phylogenetic organization in the activity of bacteria sets the stage for characterizing the functional attributes of bacterial taxonomic groups. Connecting identity with function in this way will allow scientists to begin building a mechanistic understanding of how bacterial community composition regulates critical ecosystem functions.

  9. Phylogenetic organization of bacterial activity

    PubMed Central

    Morrissey, Ember M; Mau, Rebecca L; Schwartz, Egbert; Caporaso, J Gregory; Dijkstra, Paul; van Gestel, Natasja; Koch, Benjamin J; Liu, Cindy M; Hayer, Michaela; McHugh, Theresa A; Marks, Jane C; Price, Lance B; Hungate, Bruce A

    2016-01-01

    Phylogeny is an ecologically meaningful way to classify plants and animals, as closely related taxa frequently have similar ecological characteristics, functional traits and effects on ecosystem processes. For bacteria, however, phylogeny has been argued to be an unreliable indicator of an organism's ecology owing to evolutionary processes more common to microbes such as gene loss and lateral gene transfer, as well as convergent evolution. Here we use advanced stable isotope probing with 13C and 18O to show that evolutionary history has ecological significance for in situ bacterial activity. Phylogenetic organization in the activity of bacteria sets the stage for characterizing the functional attributes of bacterial taxonomic groups. Connecting identity with function in this way will allow scientists to begin building a mechanistic understanding of how bacterial community composition regulates critical ecosystem functions. PMID:26943624

  10. [The vitamin D endocrine system].

    PubMed

    Castro, Luiz Claudio Gonçalves de

    2011-11-01

    The vitamin D endocrine system comprises a group of 7-dehydrocholesterol-derived secosteroid molecules, including its active metabolite 1,25-dihydroxy-vitamin D (1,25(OH)(2)D), its precursors and other metabolites, its binding protein (DBP) and nuclear receptor (VDR), as well as cytochrome P450 complex enzymes participating in activation and inactivation pathways of those molecules. The biologic effects of 1,25(OH)(2)D are mediated by VDR, a ligand-activated transcription factor which is a member of the nuclear receptors family, spread in almost all human cells. In addition to its classic role in the regulation of calcium metabolism and bone health, evidence suggests that 1,25(OH)(2)D directly or indirectly modulates about 3% of the human genome, participating in the regulation of chief functions of systemic homeostasis, such as cell growth, differentiation and apoptosis, regulation of immune, cardiovascular and musculoskeletal systems, and insulin metabolism. Given the critical influence of the vitamin D endocrine system in many processes of systemic metabolic equilibrium, the laboratory assays available for the evaluation of this system have to present high accuracy and reproducibility, enabling the establishment of cutoff points that, beyond being consensually accepted, reliably express the vitamin D status of the organism, and the respective clinical-metabolic impacts on the global health of the individual.

  11. [Disperse endocrine system and APUD concept].

    PubMed

    Mil'to, I V; Sukhodolo, I V; Gereng, E A; Shamardina, L A

    2011-01-01

    This review describes the problems of disperse endocrine system and APUD-system morphology, summarizes some debatable issues of single endocrine cell biology. The data presented refer to the history of both systems discovery, morphological methods of their study, developmental sources, their structural organization and physiological roles of their cells. The significance of single endocrine cells in the regulation of the organism functions is discussed.

  12. Endocrine expression of the active form of TGF-beta1 in the TGF-beta1 null mice fails to ameliorate lethal phenotype.

    PubMed

    Longenecker, Glenn; Thyagarajan, Tamizchelvi; Nagineni, Chandrasekharam N; Flanders, Kathleen C; Factor, Valentina; Miller, Georgina; Ward, Jerrold M; Nalca, Aysegul; Rangnekar, Vivek M; Thorgeirsson, Snorri; Kulkarni, Ashok B

    2002-04-01

    TGF-beta1 null mice die by 3 to 4 weeks of age due to a severe autoimmune-mediated multifocal inflammation resulting in multi-organ failure. To assess the therapeutic potential of circulating levels of active TGF-beta1, we generated mice with endocrine expression of active TGF-beta1 on a TGF-beta1 null background (TGF-beta1 (-/-/TG)) by crossing TGF-beta1(+/-) mice with transgenic mice (TG) that express recombinant TGF-beta1 specifically in the liver and secrete it in the blood. The TGF-beta1 (-/-/TG) mice exhibit a survival profile similar to the TGF-beta1 (-/-) mice indicating a failure to rescue the lethal phenotype. However, serum TGF-beta1 levels in the TGF-beta1 (-/-/TG) mice were restored to near normal levels with expression in all the tissues, notably in the kidney and spleen. Histopathology showed reduced inflammation in the target tissues, especially in the heart. Interestingly, unlike TGF-beta1 (-/-) mice, the TGF-beta1 (-/-/TG) mice have glomerulonephritis in their kidneys similar to the TG mice. Thus, the phenotype of TGF-beta1 (-/-/TG) animal model indicates the potential role of circulating active-TGF-beta1 in reducing inflammation, but its failure to rescue lethality in TGF-beta1 null mice indicates a critical autocrine role of TGF-beta1.

  13. Impact of ozonation on ecotoxicity and endocrine activity of tertiary treated wastewater effluent.

    PubMed

    Altmann, Dominik; Schaar, Heidemarie; Bartel, Cordula; Schorkopf, Dirk Louis P; Miller, Ingrid; Kreuzinger, Norbert; Möstl, Erich; Grillitsch, Britta

    2012-07-01

    Tertiary wastewater treatment plant effluent before and after ozonation (0.6-1.1g O₃/g DOC) was tested for aquatic ecotoxicity in a battery of standardised microbioassays with green algae, daphnids, and zebrafish eggs. In addition, unconjugated estrogen and 17β-hydroxyandrogen immunoreactive substances were quantified by means of enzyme immunoassays, and endocrine effects were analysed in a 21-day fish screening assay with adult male and female medaka (Oryzias latipes). Ozonation decreased estrogen-immunoreactivity by 97.7±1.2% and, to a lesser extent, androgen-immunoreactivity by 56.3±16.5%. None of the short-term exposure ecotoxicity tests revealed any adverse effects of the tertiary effluent, neither before nor after the ozonation step. Similarly in the fish screening assay, reproductive fitness parameters showed no effects attributed to micropollutants, and no detrimental effects of the effluents were observed. Based on the presented screening, ozonation effectively reduced steroid hormone levels in the wastewater treatment plant effluent without increasing the effluent's ecotoxicity. PMID:22551818

  14. Multi-Criteria Decision Analysis of Test Endpoints for Detecting the Effects of Endocrine Active Substances in Fish Full Life Cycle Tests

    EPA Science Inventory

    Fish full life cycle (FFLC) tests are increasingly required in the ecotoxicological assessment of endocrine active substances. However, FFLC tests have not been internationally standardized or validated, and it is currently unclear how such tests should best be designed to provid...

  15. Mechanistic Computational Model of Steroidgenesis in H295R Cells: Role of (Oxysterols and Cell Proliferation to Improve Predictability of Biochemical Response to Endocrine Active Chemical-Metyrapone

    EPA Science Inventory

    The human adrenocortical carcinoma cell line H295R is being used as an in vitro steroidogenesis screening assay to assess the impact of endocrine active chemicals (EACs) capable of altering steroid biosynthesis. To enhance the interpretation and quantitative application of measur...

  16. Use of an In Vitro, Nuclear Receptor Assay Panel to Characterize the Endocrine-Disrupting Activity Load of Wastewater Treatment Plant Effluent Extracts

    EPA Science Inventory

    Use of an In Vitro, Nuclear Receptor Assay Panel to Characterize the Endocrine-Disrupting Activity Load of Wastewater Treatment Plant Effluent Extracts Katie B. Paul 1.2, Ruth Marfil-Vega 1 Marc A. Mills3, Steve 0. Simmons2, Vickie S. Wilson4, Kevin M. Crofton2 10ak Rid...

  17. THE INFLUENCE OF SERUM BINDING PROTEINS AND FEEDBACK CONTROL OF SERUM ESTRADIOL LEVELS ON THE COMPARATIVE POTENCY OF ENDOCRINE ACTIVE COMPOUNDS

    EPA Science Inventory

    THE INFLUENCE OF SERUM BINDING PROTEINS ON THE COMPARATIVE RECEPTOR BINDING POTENCY OF ENDOCRINE ACTIVE COMPOUNDS. JG Teeguarden1 and HA Barton2. 1ICF Consulting, Research Triangle Park NC; 2US EPA, ORD, NHEERL, ETD, Pharmacokinetics Branch, RTP, NC.

    Accurate comparison of...

  18. Computational Model of Steroidogenesis in Human H295R Cells to Predict Biochemical Response to Endocrine Active Chemicals: Model Development for Metyrapone

    EPA Science Inventory

    BACKGROUND: An in vitro steroidogenesis assay using the human adrenocortical carcinoma cells H295R is being evaluated as a possible toxicity screening approach to detect and assess the impact of endocrine active chemicals (EAC) capable of altering steroid biosynthesis. Interpreta...

  19. Endocrine disrupting activities of surface water associated with a West Virginia oil and gas industry wastewater disposal site.

    PubMed

    Kassotis, Christopher D; Iwanowicz, Luke R; Akob, Denise M; Cozzarelli, Isabelle M; Mumford, Adam C; Orem, William H; Nagel, Susan C

    2016-07-01

    Currently, >95% of end disposal of hydraulic fracturing wastewater from unconventional oil and gas operations in the US occurs via injection wells. Key data gaps exist in understanding the potential impact of underground injection on surface water quality and environmental health. The goal of this study was to assess endocrine disrupting activity in surface water at a West Virginia injection well disposal site. Water samples were collected from a background site in the area and upstream, on, and downstream of the disposal facility. Samples were solid-phase extracted, and extracts assessed for agonist and antagonist hormonal activities for five hormone receptors in mammalian and yeast reporter gene assays. Compared to reference water extracts upstream and distal to the disposal well, samples collected adjacent and downstream exhibited considerably higher antagonist activity for the estrogen, androgen, progesterone, glucocorticoid and thyroid hormone receptors. In contrast, low levels of agonist activity were measured in upstream/distal sites, and were inhibited or absent at downstream sites with significant antagonism. Concurrent analyses by partner laboratories (published separately) describe the analytical and geochemical profiling of the water; elevated conductivity as well as high sodium, chloride, strontium, and barium concentrations indicate impacts due to handling of unconventional oil and gas wastewater. Notably, antagonist activities in downstream samples were at equivalent authentic standard concentrations known to disrupt reproduction and/or development in aquatic animals. Given the widespread use of injection wells for end-disposal of hydraulic fracturing wastewater, these data raise concerns for human and animal health nearby. PMID:27073166

  20. Endocrine disrupting activities of surface water associated with a West Virginia oil and gas industry wastewater disposal site

    USGS Publications Warehouse

    Kassotis, Christopher D.; Iwanowicz, Luke; Akob, Denise M.; Cozzarelli, Isabelle M.; Mumford, Adam; Orem, William H.; Nagel, Susan C.

    2016-01-01

    Currently, >95% of end disposal of hydraulic fracturing wastewater from unconventional oil and gas operations in the US occurs via injection wells. Key data gaps exist in understanding the potential impact of underground injection on surface water quality and environmental health. The goal of this study was to assess endocrine disrupting activity in surface water at a West Virginia injection well disposal site. Water samples were collected from a background site in the area and upstream, on, and downstream of the disposal facility. Samples were solid-phase extracted, and extracts assessed for agonist and antagonist hormonal activities for five hormone receptors in mammalian and yeast reporter gene assays. Compared to reference water extracts upstream and distal to the disposal well, samples collected adjacent and downstream exhibited considerably higher antagonist activity for the estrogen, androgen, progesterone, glucocorticoid and thyroid hormone receptors. In contrast, low levels of agonist activity were measured in upstream/distal sites, and were inhibited or absent at downstream sites with significant antagonism. Concurrent analyses by partner laboratories (published separately) describe the analytical and geochemical profiling of the water; elevated conductivity as well as high sodium, chloride, strontium, and barium concentrations indicate impacts due to handling of unconventional oil and gas wastewater. Notably, antagonist activities in downstream samples were at equivalent authentic standard concentrations known to disrupt reproduction and/or development in aquatic animals. Given the widespread use of injection wells for end-disposal of hydraulic fracturing wastewater, these data raise concerns for human and animal health nearby.

  1. Endocrine Tumor: Overview

    MedlinePlus

    ... a roadmap to this full guide. About the endocrine system The endocrine system is made up of cells that produce hormones. ... of sugar in the blood. Part of the endocrine system is the neuroendocrine system, which is made up ...

  2. When hospitals limit organizing activity.

    PubMed

    Gilmore, C B

    1988-01-01

    Since 1974, when the NLRA was extended to cover nonprofit medical institutions, hospitals have been faced with the challenge of accommodating their employees' right to engage in organizing and concerted activities while preventing such activities from disrupting patient care. Some hospitals have sought to protect the interests of patients by prohibiting solicitation and distribution in all areas to which patients and visitors have access. The Board and the courts have generally found such rules overly broad and violative of employee rights under the NLRA. In the following survey of cases involving solicitation/distribution rules, the author points out that the courts have consistently evaluated these rules on the basis of the special nature of the hospital setting. Accordingly, advises the author, hospital administrators who are promulgating distributions and solicitation rules covering a given location must consider the individual characteristics of that location, namely, its physical layout, the type of work performed there, and the availability of alternate space.

  3. Alterations in development of reproductive and endocrine systems of wildlife populations exposed to endocrine-disrupting contaminants.

    PubMed

    Guillette, L J; Gunderson, M P

    2001-12-01

    Wildlife and human populations are affected by contaminants in natural settings. This problem has been a growing concern over the last decade with the realization that various environmental chemicals can alter the development and functioning of endocrine organs, cells and target tissues. Documented disruptions or alterations in reproductive activity, morphology or physiology in wildlife populations have been correlated with contaminant-induced modifications in endocrine system functioning. Alterations of the endocrine system are complex, and not limited to a particular organ or molecular mechanism. For instance, contaminants have been shown to (1) act as hormone receptor agonists or antagonists, (2) alter hormone production at its endocrine source, (3) alter the release of stimulatory or inhibitory hormones from the pituitary or hypothalamus, (4) alter hepatic enzymatic biotransformation of hormones, and (5) alter the concentration or functioning of serum-binding proteins, altering free hormone concentrations in the serum. This review focuses on two of these alterations, altered hormone synthesis and hepatic biotransformation, as a number of recent studies indicate that these actions are important components of endocrine disruption in developing organisms. The possible role of contaminants in altering sex determination mechanisms is also examined.

  4. Psychological aspects of endocrine disease.

    PubMed

    Sonino, N; Guidi, J; Fava, G A

    2015-03-01

    This review illustrates how an innovative psychoneuroendocrine approach to endocrine patients may improve their management. Important psychological issues pertain to all the different phases of an endocrine disorder. Before disease onset, stressful life events may play a pathogenetic role and, together with chronic stress, may contribute to a cumulative burden also called allostatic load; psychological and psychiatric symptoms are common both in the prodromal and in the active phase of illness; after cure or remission, there could be residual symptoms and impaired quality of life that deserve attention. All these aspects should be taken into consideration and introduced in current endocrine care and practice.

  5. Endocrine assessment of ovarian cycle activity in wild female mountain gorillas (Gorilla beringei beringei).

    PubMed

    Habumuremyi, Sosthene; Stephens, Colleen; Fawcett, Katie A; Deschner, Tobias; Robbins, Martha M

    2016-04-01

    endocrine patterns of variation in fertility depending on parity, mating behavior, and pregnancy success in a critically endangered great ape.

  6. Endocrine assessment of ovarian cycle activity in wild female mountain gorillas (Gorilla beringei beringei).

    PubMed

    Habumuremyi, Sosthene; Stephens, Colleen; Fawcett, Katie A; Deschner, Tobias; Robbins, Martha M

    2016-04-01

    endocrine patterns of variation in fertility depending on parity, mating behavior, and pregnancy success in a critically endangered great ape. PMID:26875514

  7. Effect of endocrine disrupters on photosystem II energy fluxes of green algae and cyanobacteria.

    PubMed

    Perron, Marie-Claude; Juneau, Philippe

    2011-05-01

    Among the numerous toxics found in the aquatic environment, endocrine disrupters can interfere with the normal functioning of the endocrine system of several organisms, leading to important consequences. Even if algae and cyanobacteria are non-target organisms without endocrine system, our goals were to verify if endocrine disrupters can affect photosynthetic activity and how energy flows through photosystem II (PSII) were altered. To reach these objectives, we exposed, for 15 min, two green algae (Chlamydomonas reinhardtii strain CC125, Pseudokirchneriella subcapitata strain CPCC37) and a toxic and a non-toxic strain of Microcystis aeruginosa (CPCC299 and CPCC632 respectively) to 4-octylphenol, 4-nonylphenol and β-estradiol at concentrations ranging from 0.1 to 5 μg/mL. We have shown for the first time that endocrine disrupters may have drastic effects on PSII energy fluxes. Furthermore, we showed that various species have different sensitivity to endocrine disrupters. P. subcapitata was tolerant to each endocrine disrupter tested, while flows of energy through PSII were affected similarly, but at different extent, for the other species. Cyanobacterial PSII energy fluxes were more affected than green algae, suggesting that the prokaryotic characteristics of these organisms are responsible of their high sensitivity.

  8. Analysis of eight oil spill dispersants using rapid, in vitro tests for endocrine and other biological activity.

    PubMed

    Judson, Richard S; Martin, Matthew T; Reif, David M; Houck, Keith A; Knudsen, Thomas B; Rotroff, Daniel M; Xia, Menghang; Sakamuru, Srilatha; Huang, Ruili; Shinn, Paul; Austin, Christopher P; Kavlock, Robert J; Dix, David J

    2010-08-01

    The Deepwater Horizon oil spill has led to the use of >1 M gallons of oil spill dispersants, which are mixtures of surfactants and solvents. Because of this large scale use there is a critical need to understand the potential for toxicity of the currently used dispersant and potential alternatives, especially given the limited toxicity testing information that is available. In particular, some dispersants contain nonylphenol ethoxylates (NPEs), which can degrade to nonylphenol (NP), a known endocrine disruptor. Given the urgent need to generate toxicity data, we carried out a series of in vitro high-throughput assays on eight commercial dispersants. These assays focused on the estrogen and androgen receptors (ER and AR), but also included a larger battery of assays probing other biological pathways. Cytotoxicity in mammalian cells was also quantified. No activity was seen in any AR assay. Two dispersants showed a weak ER signal in one assay (EC50 of 16 ppm for Nokomis 3-F4 and 25 ppm for ZI-400). NPs and NPEs also had a weak signal in this same ER assay. Note that Corexit 9500, the currently used product, does not contain NPEs and did not show any ER activity. Cytotoxicity values for six of the dispersants were statistically indistinguishable, with median LC50 values approximately 100 ppm. Two dispersants, JD 2000 and SAF-RON GOLD, were significantly less cytotoxic than the others with LC50 values approaching or exceeding 1000 ppm. PMID:20602530

  9. Analysis of eight oil spill dispersants using rapid, in vitro tests for endocrine and other biological activity.

    PubMed

    Judson, Richard S; Martin, Matthew T; Reif, David M; Houck, Keith A; Knudsen, Thomas B; Rotroff, Daniel M; Xia, Menghang; Sakamuru, Srilatha; Huang, Ruili; Shinn, Paul; Austin, Christopher P; Kavlock, Robert J; Dix, David J

    2010-08-01

    The Deepwater Horizon oil spill has led to the use of >1 M gallons of oil spill dispersants, which are mixtures of surfactants and solvents. Because of this large scale use there is a critical need to understand the potential for toxicity of the currently used dispersant and potential alternatives, especially given the limited toxicity testing information that is available. In particular, some dispersants contain nonylphenol ethoxylates (NPEs), which can degrade to nonylphenol (NP), a known endocrine disruptor. Given the urgent need to generate toxicity data, we carried out a series of in vitro high-throughput assays on eight commercial dispersants. These assays focused on the estrogen and androgen receptors (ER and AR), but also included a larger battery of assays probing other biological pathways. Cytotoxicity in mammalian cells was also quantified. No activity was seen in any AR assay. Two dispersants showed a weak ER signal in one assay (EC50 of 16 ppm for Nokomis 3-F4 and 25 ppm for ZI-400). NPs and NPEs also had a weak signal in this same ER assay. Note that Corexit 9500, the currently used product, does not contain NPEs and did not show any ER activity. Cytotoxicity values for six of the dispersants were statistically indistinguishable, with median LC50 values approximately 100 ppm. Two dispersants, JD 2000 and SAF-RON GOLD, were significantly less cytotoxic than the others with LC50 values approaching or exceeding 1000 ppm.

  10. Analysis of Eight Oil Spill Dispersants Using Rapid, In Vitro Tests for Endocrine and Other Biological Activity

    PubMed Central

    Judson, Richard S.; Martin, Matthew T.; Reif, David M.; Houck, Keith A.; Knudsen, Thomas B.; Rotroff, Daniel M.; Xia, Menghang; Sakamuru, Srilatha; Huang, Ruili; Shinn, Paul; Austin, Christopher P.; Kavlock, Robert J.; Dix, David J.

    2010-01-01

    The Deepwater Horizon oil spill has led to the use of >1 M gallons of oil spill dispersants, which are mixtures of surfactants and solvents. Because of this large scale use there is a critical need to understand the potential for toxicity of the currently used dispersant and potential alternatives, especially given the limited toxicity testing information that is available. In particular, some dispersants contain nonylphenol ethoxylates (NPEs), which can degrade to nonylphenol (NP), a known endocrine disruptor. Given the urgent need to generate toxicity data, we carried out a series of in vitro high-throughput assays on eight commercial dispersants. These assays focused on the estrogen and androgen receptors (ER and AR), but also included a larger battery of assays probing other biological pathways. Cytotoxicity in mammalian cells was also quantified. No activity was seen in any AR assay. Two dispersants showed a weak ER signal in one assay (EC50 of 16 ppm for Nokomis 3-F4 and 25 ppm for ZI-400). NPs and NPEs also had a weak signal in this same ER assay. Note that Corexit 9500, the currently used product, does not contain NPEs and did not show any ER activity. Cytotoxicity values for six of the dispersants were statistically indistinguishable, with median LC50 values ∼100 ppm. Two dispersants, JD 2000, SAF-RON GOLD, were significantly less cytotoxic than the others with LC50 values approaching or exceeding 1000 ppm. PMID:20602530

  11. Uncertainties in biological responses that influence hazard or risk approaches to the regulation of endocrine active substances

    EPA Science Inventory

    Endocrine Disrupting Chemicals (EDCs) may have delayed or transgenerational effects and display non-monotonic dose response relationships (NMDRs) that require careful consideration when determining environmental hazards. The case studies evaluated for the SETAC Pellston Workshop&...

  12. Endocrine disrupting chemicals

    PubMed Central

    Yeung, Bonnie HY; Wan, Hin T; Law, Alice YS

    2011-01-01

    In the past 200 years, an enormous number of synthetic chemicals with diverse structural features have been produced for industrial, medical and domestic purposes. These chemicals, originally thought to have little or no biological toxicity, are widely used in our daily lives as well as are commonly present in foods. It was not until the first World Wildlife Federation Wingspread Conference held in 1994 were concerns about the endocrine disrupting (ED) effects of these chemicals articulated. The potential hazardous effects of endocrine disrupting chemicals (EDCs) on human health and ecological well-being are one of the global concerns that affect the health and propagation of human beings. Considerable numbers of studies indicated that endocrine disruption is linked to “the developmental basis of adult disease,” highlighting the significant effects of EDC exposure on a developing organism, leading to the propensity of an individual to develop a disease or dysfunction in later life. In this review, we intend to provide environmental, epidemiological and experimental data to associate pollutant exposure with reproductive disorders, in particular on the development and function of the male reproductive system. Possible effects of pollutant exposure on the processes of embryonic development, like sex determination and masculinization are described. In addition, the effects of pollutant exposure on hypothalamus-pituitary-gonadal axis, testicular signaling, steroidogenesis and spermatogenesis are also discussed. PMID:22319671

  13. Endocrine disruptors and obesity.

    PubMed

    Heindel, Jerrold J; Newbold, Retha; Schug, Thaddeus T

    2015-11-01

    The increasing incidence of obesity is a serious global public health challenge. Although the obesity epidemic is largely fueled by poor nutrition and lack of exercise, certain chemicals have been shown to potentially have a role in its aetiology. A substantial body of evidence suggests that a subclass of endocrine-disrupting chemicals (EDCs), which interfere with endocrine signalling, can disrupt hormonally regulated metabolic processes, especially if exposure occurs during early development. These chemicals, so-called 'obesogens' might predispose some individuals to gain weight despite their efforts to limit caloric intake and increase levels of physical activity. This Review discusses the role of EDCs in the obesity epidemic, the latest research on the obesogen concept, epidemiological and experimental findings on obesogens, and their modes of action. The research reviewed here provides knowledge that health scientists can use to inform their research and decision-making processes. PMID:26391979

  14. Emerging and priority contaminants with endocrine active potentials in sediments and fish from the River Po (Italy).

    PubMed

    Luigi, Viganò; Giuseppe, Mascolo; Claudio, Roscioli

    2015-09-01

    There is a substantial lack of information on most priority pollutants, related contamination trends, and (eco)toxicological risks for the major Italian watercourse, the River Po. Targeting substances of various uses and origins, this study provides the first systematic data for the River Po on a wide set of priority and emerging chemicals, all characterized by endocrine-active potentials. Flame retardants, natural and synthetic hormones, surfactants, personal care products, legacy pollutants, and other chemicals have been investigated in sediments from the River Po and its tributary, the River Lambro, as well as in four fish species from the final section of the main river. With few exceptions, all chemicals investigated could be tracked in the sediments of the main Italian river for tens or hundreds of kilometres downstream from the Lambro tributary. Nevertheless, the results indicate that most of these contaminants, i.e., TBBPA, TCBPA, TBBPA-bis, DBDPE, HBCD, BPA, OP, TCS, TCC, AHTN, HHCB, and DDT, individually pose a negligible risk to the River Po. In contrast, PBDE, PCB, natural and synthetic estrogens, and to a much lower extent NP, were found at levels of concern either to aquatic life or human health. Adverse biological effects and prohibition of fish consumption deserve research attention and management initiatives, also considering the transport of contaminated sediments to transitional and coastal environments of the Italian river. PMID:25956513

  15. Effect of Endocrine Disruptor Pesticides: A Review

    PubMed Central

    Mnif, Wissem; Hassine, Aziza Ibn Hadj; Bouaziz, Aicha; Bartegi, Aghleb; Thomas, Olivier; Roig, Benoit

    2011-01-01

    Endocrine disrupting chemicals (EDC) are compounds that alter the normal functioning of the endocrine system of both wildlife and humans. A huge number of chemicals have been identified as endocrine disruptors, among them several pesticides. Pesticides are used to kill unwanted organisms in crops, public areas, homes and gardens, and parasites in medicine. Human are exposed to pesticides due to their occupations or through dietary and environmental exposure (water, soil, air). For several years, there have been enquiries about the impact of environmental factors on the occurrence of human pathologies. This paper reviews the current knowledge of the potential impacts of endocrine disruptor pesticides on human health. PMID:21776230

  16. Effect of endocrine disruptor pesticides: a review.

    PubMed

    Mnif, Wissem; Hassine, Aziza Ibn Hadj; Bouaziz, Aicha; Bartegi, Aghleb; Thomas, Olivier; Roig, Benoit

    2011-06-01

    Endocrine disrupting chemicals (EDC) are compounds that alter the normal functioning of the endocrine system of both wildlife and humans. A huge number of chemicals have been identified as endocrine disruptors, among them several pesticides. Pesticides are used to kill unwanted organisms in crops, public areas, homes and gardens, and parasites in medicine. Human are exposed to pesticides due to their occupations or through dietary and environmental exposure (water, soil, air). For several years, there have been enquiries about the impact of environmental factors on the occurrence of human pathologies. This paper reviews the current knowledge of the potential impacts of endocrine disruptor pesticides on human health.

  17. Quantitative structure-activity relationship modeling on in vitro endocrine effects and metabolic stability involving 26 selected brominated flame retardants.

    PubMed

    Harju, Mikael; Hamers, Timo; Kamstra, Jorke H; Sonneveld, Edwin; Boon, Jan P; Tysklind, Mats; Andersson, Patrik L

    2007-04-01

    In this work, quantitative structure-activity relationships (QSARs) were developed to aid human and environmental risk assessment processes for brominated flame retardants (BFRs). Brominated flame retardants, such as the high-production-volume chemicals polybrominated diphenyl ethers (PBDEs), tetrabromobisphenol A, and hexabromocyclododecane, have been identified as potential endocrine disruptors. Quantitative structure-activity relationship models were built based on the in vitro potencies of 26 selected BFRs. The in vitro assays included interactions with, for example, androgen, progesterone, estrogen, and dioxin (aryl hydrocarbon) receptor, plus competition with thyroxine for its plasma carrier protein (transthyretin), inhibition of estradiol sulfation via sulfotransferase, and finally, rate of metabolization. The QSAR modeling, a number of physicochemical parameters were calculated describing the electronic, lipophilic, and structural characteristics of the molecules. These include frontier molecular orbitals, molecular charges, polarities, log octanol/water partitioning coefficient, and two- and three-dimensional molecularproperties. Experimental properties were included and measured for PBDEs, such as their individual ultraviolet spectra (200-320 nm) and retention times on three different high-performance liquid chromatography columns and one nonpolar gas chromatography column. Quantitative structure-activity relationship models based on androgen antagonism and metabolic degradation rates generally gave similar results, suggesting that lower-brominated PBDEs with bromine substitutions in ortho positions and bromine-free meta- and para positions had the highest potencies and metabolic degradation rates. Predictions made for the constituents of the technical flame retardant Bromkal 70-5DE found BDE 17 to be a potent androgen antagonist and BDE 66, which is a relevant PBDE in environmental samples, to be only a weak antagonist.

  18. Test concentration setting for fish in vivo endocrine screening assays.

    PubMed

    Wheeler, James R; Panter, Grace H; Weltje, Lennart; Thorpe, Karen L

    2013-08-01

    Fish in vivo screening methods to detect endocrine active substances, specifically interacting with the hypothalamic-pituitary-gonadal axis, have been developed by both the Organization for Economic Co-operation and Development (OECD) and United States Environmental Protection Agency (US-EPA). In application of these methods, i.e. regulatory testing, this paper provides a proposal on the setting of test concentrations using all available acute and chronic data and also discusses the importance of avoiding the confounding effects of systemic toxicity on endocrine endpoints. This guidance is aimed at reducing the number of false positives and subsequently the number of inappropriate definitive vertebrate studies potentially triggered by effects consequent to systemic, rather than endocrine, toxicity. At the same time it provides a pragmatic approach that maximizes the probability of detecting an effect, if it exists, thus limiting the potential for false negative outcomes.

  19. Monitoring endocrine activity in kraft mill effluent treated by aerobic moving bed bioreactor system.

    PubMed

    Chamorro, S; Pozo, G; Jarpa, M; Hernandez, V; Becerra, J; Vidal, G

    2010-01-01

    A Moving Bed Bioreactor (MBBR) was operated at three different hydraulic retention times for a period of 414 days. The fate of the extractive compounds and the estrogenic activity of the Pinus radiata kraft mill effluents were evaluated using Yeast Estrogen Screen (YES) and gas chromatography - mass spectrometry (GC-MS) detection. Results show that the MBBR reactor is able to remove between 80-83% of estrogenic activity present in the kraft mill Pinus radiata influent, where the values of the effluent's estrogenic activity ranged between 0.123-0.411 ng L(-1), expressed as estrogenic equivalent (EEqs) of 17-a-ethynylestradiol (EE2 eq.). Additionally, the biomass of the MBBR reactor accumulated estrogenic activity ranging between 0.29-0.37 ng EEqs EE2 during the different Hydraulic Retention Time (HRT) operations. The main groups present in pulp mills effluents, corresponding to fatty acids, hydrocarbons, phenols, sterols and triterpenes, were detected by solid phase extraction (SPE) and gas chromatography - mass spectrometry (GC-MS). The results suggest that the sterols produce the estrogenic activity in the evaluated effluent. PMID:20595766

  20. Endocrine Labomas

    PubMed Central

    Dutta, Deep; Chowdhury, Subhankar

    2012-01-01

    Laboratory endocrinology forms an integral part of 21st century endocrinology. Perhaps, no other specialty of medicine is as closely associated with laboratory as endocrinology. This review intends to highlight the challenges faced by an endocrinologist before interpreting a hormone assay report. This review by no means is holistic but intends to highlight some of the pitfalls of laboratory endocrinology and arouse further interest in this important but neglected section of endocrinology. Lack of standardization, as well as rigorous implementation is some of the major challenges facing endocrine assays in our country. It is essential to be aware not only of the details of the method of analysis of a hormone, the pre-analytical requisites, but also disease-specific analytical issues to prevent unnecessary concern both for the patient, as well as the treating physician, as well as needless investigations. Problems with interpretation of serum prolactin, thyroglobulin, steroid hormone assays, rennin assay and vitamin-D assay have been highlighted. PMID:23565398

  1. Endocrine Disruptors

    PubMed Central

    2015-01-01

    Law and science combine in the estimation of risks from endocrine disruptors (EDs) and actions for their regulation. For both, dose–response models are the causal link between exposure and probability (or percentage change) of adverse response. The evidence that leads to either regulations or judicial decrees is affected by uncertainty and limited knowledge, raising difficult policy issues that we enumerate and discuss. In the United States, some courts have dealt with EDs, but causation based on animal studies has been a stumbling block for plaintiffs seeking compensation, principally because those courts opt for epidemiological evidence. The European Union (EU) has several regulatory tools and ongoing research on the risks associated with bisphenol A, under the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) Regulation and other regulations or directives. The integration of a vast (in kind and in scope) number of research papers into a statement of causation for either policy or to satisfy legal requirements, in both the United States and the EU, relies on experts. We outline the discursive dilemma and issues that may affect consensus-based results and a Bayesian causal approach that accounts for the evolution of information, yielding both value of information and flexibility associated with public choices. PMID:26740809

  2. Endocrine-active compound evaluation: qualitative and quantitative histomorphological assessment of zebrafish gonads after bisphenol-A exposure.

    PubMed

    Molina, Ana M; Lora, Antonio J; Blanco, Alfonso; Monterde, José G; Ayala, Nahum; Moyano, Rosario

    2013-02-01

    There is great social concern about the risk involved from exposure to BPA as an endocrine disrupter in humans, as well as the possible repercussion of this chemical on the environment. In this study, the short-term effects of BPA at a gonadal level were assessed by means of different biomarkers in a model animal organism in vogue, the zebrafish (Danio rerio). For this purpose, 60 female zebrafish aged 16 weeks were used. These were exposed for 14 days in aquariums (following OECD Directive no.204) to BPA concentrations of 1, 10, 100 and 1000 μg/L, in addition to a control batch. After the exposure period, the zebrafish were sacrificed and samples taken for a histopathological study by light and electron microscopy and morphometric analysis. During the fourteen days of exposure, water samples were taken from the aquariums to analyze the BPA levels. The BPA concentration in the fish and the water was determined by LC-MS/MS. The gonads of the zebrafish exposed to the BPA had a normal external appearance and there were no variations in their size or body weight. An accumulation of BPA was produced in the zebrafish tissues, and this increased as the BPA concentration to which the fish were exposed did. In the histopathological and morphometric studies, multiple alterations were observed in the zebrafish ovaries, particularly highlighting the vacuolization of the follicular cytoplasm, a great degeneration of all the cell components, and an important increase in the percentage of atretic follicles as from concentrations of 100 and 1000 μg/L of BPA, verified by morphometry. These data indicate that morphological endpoints are sufficiently sensitive to individuate early effects of environmental concentration of BPA on gonads after two weeks of exposure. PMID:23219663

  3. Canine toys and training devices as sources of exposure to phthalates and bisphenol A: quantitation of chemicals in leachate and in vitro screening for endocrine activity.

    PubMed

    Wooten, Kimberly J; Smith, Philip N

    2013-11-01

    Chewing and mouthing behaviors exhibited by pet dogs are likely to lead to oral exposures to a variety of environmental chemicals. Products intended for chewing and mouthing uses include toys and training devices that are often made of plastics. The goal of the current study was to determine if a subset of phthalates and bisphenol A (BPA), endocrine disrupting chemicals commonly found in plastics, leach out of dog toys and training devices (bumpers) into synthetic canine saliva. In vitro assays were used to screen leachates for endocrine activity. Bumper leachates were dominated by di-2-ethylhexyl phthalate (DEHP) and BPA, with concentrations reaching low μg mL(-1) following short immersions in synthetic saliva. Simulated chewing of bumpers during immersion in synthetic saliva increased concentrations of phthalates and BPA as compared to new bumpers, while outdoor storage had variable effects on concentrations (increased DEHP; decreased BPA). Toys leached substantially lower concentrations of phthalates and BPA, with the exception of one toy which leached considerable amounts of diethyl phthalate. In vitro assays indicated anti-androgenic activity of bumper leachates, and estrogenic activity of both bumper and toy leachates. These results confirm that toys and training devices are potential sources of exposure to endocrine disrupting chemicals in pet dogs. PMID:24007620

  4. Comparison of UV photolysis, nanofiltration, and their combination to remove hormones from a drinking water source and reduce endocrine disrupting activity.

    PubMed

    Sanches, Sandra; Rodrigues, Alexandre; Cardoso, Vitor V; Benoliel, Maria J; Crespo, João G; Pereira, Vanessa J

    2016-06-01

    A sequential water treatment combining low pressure ultraviolet direct photolysis with nanofiltration was evaluated to remove hormones from water, reduce endocrine disrupting activity, and overcome the drawbacks associated with the individual processes (production of a nanofiltration-concentrated retentate and formation of toxic by-products). 17β-Estradiol, 17α-ethinylestradiol, estrone, estriol, and progesterone were spiked into a real water sample collected after the sedimentation process of a drinking water treatment plant. Even though the nanofiltration process alone showed similar results to the combined treatment in terms of the water quality produced, the combined treatment offered advantage in terms of the load of the retentate and decrease in the endocrine-disrupting activity of the samples. Moreover, the photolysis by-products produced, with higher endocrine disrupting activity than the parent compounds, were effectively retained by the membrane. The combination of direct LP/UV photolysis with nanofiltration is promising for a drinking water utility that needs to cope with sudden punctual discharges or deterioration of the water quality and wants to decrease the levels of chemicals in the nanofiltration retentate. PMID:26924700

  5. Fluorinated alkyl substances and technical mixtures used in food paper-packaging exhibit endocrine-related activity in vitro.

    PubMed

    Rosenmai, A K; Taxvig, C; Svingen, T; Trier, X; van Vugt-Lussenburg, B M A; Pedersen, M; Lesné, L; Jégou, B; Vinggaard, A M

    2016-07-01

    Migration of chemicals from packaging materials to foods may lead to human exposure. Polyfluoroalkyl substances (PFAS) can be used in technical mixtures (TMs) for use in food packaging of paper and board, and PFAS have been detected in human serum and umbilical cord blood. The specific structures of the PFAS in TMs are often unknown, but polyfluorinated alkyl phosphate esters (PAPs) have been characterized in TMs, food packaging, and in food. PAPs can be metabolized into fluorotelomer alcohols (FTOHs) and perfluoroalkyl carboxylic acids (PFCAs). Some PFAS have endocrine activities, highlighting the need to investigate these effects. Herein, we studied the endocrine activity of less characterized PFAS, including short-chain PFCAs and FTOHs, PAPs, and TMs of unknown chemical composition. Long-chain PFCAs were also included. We applied seven assays covering effects on estrogen, glucocorticoid, androgen, and peroxisome proliferator-activated receptor (PPAR) activity, as well as steroidogenesis in vitro and ex vivo. In general, PAPs, FTOHs, TMs, and long-chain PFCAs showed estrogenic activity through receptor activation and/or increasing 17β-estradiol levels. Furthermore, short- and long-chain PFCAs activated PPARα and PPARγ. Collectively, this means that (i) PAPs, FTOHs, and PFCAs exhibit endocrine activity through distinct and sometimes different mechanisms, (ii) two out of three tested TMs exhibited estrogenic activity, and (iii) short-chain FTOHs showed estrogenic activity and short-chain PFCAs generally activate both PPARα and PPARγ with similar potency and efficacy as long-chain PFCAs. In conclusion, several new and divergent toxicological targets were identified for different groups of PFAS.

  6. MOBILIZATION OF ENDOCRINE DISRUPTING CHEMICALS AND ESTROGENIC ACTIVITY IN SIMULATED RAINFALL RUNOFF FROM LAND-APPLIED BIOSOLIDS

    PubMed Central

    Giudice, Ben D.; Young, Thomas M.

    2012-01-01

    Municipal biosolids are commonly applied to land as soil amendment or fertilizer as a form of beneficial reuse of what could otherwise be viewed as waste. Balanced against this benefit are potential risks to groundwater and surface water quality from constituents that may be mobilized during storm events. The objective of the present study was to characterize the mobilization of selected endocrine disrupting compounds (EDCs), heavy metals, and total estrogenic activity in rainfall runoff from land-applied biosolids. Rainfall simulations were conducted on soil plots amended with biosolids. Surface runoff and leachate was collected and analyzed for the EDCs bisphenol A, 17α-ethynylestradiol, triclocarban, triclosan, octylphenol, and nonylphenol; a suite of sixteen metals; and estrogenic activity via the ER-CALUX bioassay. Triclocarban (2.3–17.3 ng/L), triclosan (<51–309 ng/L), and octylphenol (<4.9–203 ng/L) were commonly detected. Chromium (2.0–22 µg/L), cobalt (2.5–10 µg/L), nickel (28–235 µg/L), copper (14–110 µg/L), arsenic (1.2–2.7 µg/L), and selenium (0.29–12 µg/L) were quantifiable over background levels. Triclosan, nickel, and copper were detected at levels that might pose some risk to aquatic life, though levels of metals in the biosolids were well below maximum allowable regulatory limits. ER-CALUX results were mostly explained by background bisphenol A contamination and octylphenol in runoff, though unknown contributors and/or matrix effects were also found. PMID:21786314

  7. Nanotoxicity: a growing need for study in the endocrine system.

    PubMed

    Lu, Xuefei; Liu, Ying; Kong, Xiangjun; Lobie, Peter E; Chen, Chunying; Zhu, Tao

    2013-05-27

    Nanomaterials (NMs) are engineered for commercial purposes such as semiconductors, building materials, cosmetics, and drug carriers, while natural nanoparticles (NPs) already exist in the environment. Due to their unique physicochemical properties, they may interact actively with biological systems. Some of these interactions might be detrimental to human health, and therefore studies on the potential 'nanotoxicity' of these materials in different organ systems are warranted. The purpose of developing the concept of nanotoxicity is to recognize and evaluate the hazards and risks of NMs and evaluate safety. This review will summarize and discuss recent reports derived from cell lines or animal models concerning the effects of NMs on, and their application in, the endocrine system of mammalian and other species. It will present an update on current studies of the effects of some typical NMs-such as metal-based NMs, carbon-based NMs, and dendrimers-on endocrine functions, in which some effects are adverse or unwanted and others are favorable or intended. Disruption of endocrine function is associated with adverse health outcomes including reproductive failure, metabolic syndrome, and some types of cancer. Further investigations are therefore required to obtain a thorough understanding of any potential risk of pathological endocrine disruption from products containing NMs. This review aims to provide impetus for further studies on the interactions of NMs with endocrine functions.

  8. Endocrine Disruptors (Chapter 14) in Mammalian Toxicology Book

    EPA Science Inventory

    Endocrine disrupting chemicals (EDCs) are exogenous substances that alter endocrine system function(s) and consequently cause adverse health effects in intact organisms or its progeny. The endocrine system is important for a wide range of biological processes, from normal cell si...

  9. Comparison of activation media and pyrolysis temperature for activated carbons development by pyrolysis of potato peels for effective adsorption of endocrine disruptor bisphenol-A.

    PubMed

    Arampatzidou, Anastasia C; Deliyanni, Eleni A

    2016-03-15

    Activated carbon prepared from potato peels, a solid waste by product has been studied for the adsorption of an endocrine disruptor, Bisphenol-A, from aqueous solutions. The potato peels biomass was activated with H3PO4, KOH and ZnCl2 in order the effect of the activation agent to be evaluated. The activated biomass was carbonized at 400, 600 and/or 800 °C in order the effect of carbonization temperature on the texture, surface chemistry and adsorption properties to be found. The activated carbons prepared were characterized by nitrogen adsorption, Scanning Electron Microscope, thermal analysis and Fourier Transform Infrared Spectroscopy. Equilibrium adsorption data followed both Langmuir and Freundlich isotherms. Adsorption followed second order rate kinetics. The adsorption capacity calculated from the Langmuir isotherm was found 454.62 mg g(-1) at an initial pH 3 at 25 °C for the phosphoric acid activated carbon carbonized at 400 °C that proved to be the best adsorbent.

  10. Comparison of activation media and pyrolysis temperature for activated carbons development by pyrolysis of potato peels for effective adsorption of endocrine disruptor bisphenol-A.

    PubMed

    Arampatzidou, Anastasia C; Deliyanni, Eleni A

    2016-03-15

    Activated carbon prepared from potato peels, a solid waste by product has been studied for the adsorption of an endocrine disruptor, Bisphenol-A, from aqueous solutions. The potato peels biomass was activated with H3PO4, KOH and ZnCl2 in order the effect of the activation agent to be evaluated. The activated biomass was carbonized at 400, 600 and/or 800 °C in order the effect of carbonization temperature on the texture, surface chemistry and adsorption properties to be found. The activated carbons prepared were characterized by nitrogen adsorption, Scanning Electron Microscope, thermal analysis and Fourier Transform Infrared Spectroscopy. Equilibrium adsorption data followed both Langmuir and Freundlich isotherms. Adsorption followed second order rate kinetics. The adsorption capacity calculated from the Langmuir isotherm was found 454.62 mg g(-1) at an initial pH 3 at 25 °C for the phosphoric acid activated carbon carbonized at 400 °C that proved to be the best adsorbent. PMID:26707777

  11. Age and the endocrine system.

    PubMed

    Noth, R H; Mazzaferri, E L

    1985-02-01

    The pattern of age-induced changes in each endocrine system is unique. Both hormone levels and target organ responsivity are altered in the aging endocrine-cardiovascular system. Serum levels of vasopressor hormones both increase (norepinephrine) and decrease (renin, aldosterone). Target organ responses to beta-adrenergic stimulation in the heart and probably also in vascular smooth muscle decrease due to postreceptor changes. These effects contribute to the clinical problems of hypertension and orthostatic hypotension which characterize the elderly. Aging produces mild carbohydrate intolerance and a minimal increase in fasting serum glucose in healthy, nonobese individuals, primarily due to decreasing postreceptor responsiveness to insulin. Aging decreases the metabolism of thyroxine, including its conversion to triiodothyronine, but clinically significant alterations of thyroid hormone levels do not occur. Changes in the end-organ response to thyroid hormones, however, significantly alter the clinical presentation of thyroid diseases. Aging shifts the serum vasopressin-serum osmolality relationship toward higher serum vasopressin levels probably due to altered baroreceptor input, probably contributing to the tendency toward hyponatremia in the elderly. Aging slows the metabolism of cortisol, but glucocorticoid levels in the human are essentially unaltered by age. However, recent data indicate that delta-5 adrenal steroids decrease markedly in both men and women. Nodules in the anterior pituitary, the thyroid, and the adrenal increase in frequency with aging. Finally, the reproductive system is primarily altered by endocrine cell death, by unknown mechanisms, resulting in decreased estrogen and testosterone levels in women and men. This most obvious age-related endocrine change turns out to be incompletely understood and is not representative of most age-related endocrine changes. Despite characterization of these many age-related alterations in endocrine systems

  12. Developing analytical approaches to explore the connection between endocrine-active pharmaceuticals in water to effects in fish.

    PubMed

    Jones-Lepp, Tammy L; Taniguchi-Fu, Randi L; Morgan, Jade; Nance, Trevor; Ward, Matthew; Alvarez, David A; Mills, Lesley

    2015-08-01

    The emphasis of this research project was to develop and optimize a solid-phase extraction method and high-performance liquid chromatography-electrospray ionization-mass spectrometry method, such that a linkage between the detection of endocrine-active pharmaceuticals (EAPs) in the aquatic environment and subsequent effects on fish populations could eventually be studied. Four EAPs were studied: tamoxifen (TAM), exemestane (EXE), letrozole (LET), anastrozole (ANA); and three TAM metabolites: 4-hydroxytamoxifen, e/z endoxifen, and n-desmethyl tamoxifen. In aqueous matrices, the use of isotopically labeled standards for the EAPs allowed for the generation of good recoveries, greater than 80 %, and low relative standard deviations (% RSDs) (3 to 27 %). TAM metabolites had lower recoveries in the spiked water matrices: 35 to 93 % in waste/source water compared to 58 to 110 % in DI water. The precision in DI water was acceptable ranging from 8 to 38 % RSD. However, the precision in real environmental wastewaters could be poor, ranging from 15 to 120 % RSD, dependent upon unique matrix effects. In plasma, the overall recoveries of the EAPs were acceptable: 88 to 110 %, with %RSDs of 6 to 18 % (Table 3). The spiked recoveries of the TAM metabolites from plasma were good, ranging from 77 to 120 %, with %RSDs ranging from 27 to 32 %. Two of the TAM metabolites, 4-hydroxytamoxifen and n-desmethyl tamoxifen, were confirmed in most of the environmental aqueous samples. The discovery of TAM metabolites demonstrates that the source of the TAM metabolites, TAM, is constant, introducing a pseudo-persistence of this chemical into the environment. PMID:26077747

  13. Developing analytical approaches to explore the connection between endocrine-active pharmaceuticals in water to effects in fish

    USGS Publications Warehouse

    Jones-Lepp, Tammy L.; Taniguchi-Fu, Randi L.; Morgan, Jade; Nance Jr., Trevor; Ward, Matthew; Alvarez, David A.; Mills, Lesley

    2015-01-01

    The emphasis of this research project was to develop and optimize a solid-phase extraction method and highperformance liquid chromatography-electrospray ionizationmass spectrometry method, such that a linkage between the detection of endocrine-active pharmaceuticals (EAPs) in the aquatic environment and subsequent effects on fish populations could eventually be studied. Four EAPs were studied: tamoxifen (TAM), exemestane (EXE), letrozole (LET), anastrozole (ANA); and three TAM metabolites: 4- hydroxytamoxifen, e/z endoxifen, and n-desmethyl tamoxifen. In aqueous matrices, the use of isotopically labeled standards for the EAPs allowed for the generation of good recoveries, greater than 80 %, and low relative standard deviations (% RSDs) (3 to 27 %). TAM metabolites had lower recoveries in the spiked water matrices: 35 to 93 % in waste/source water compared to 58 to 110 % in DI water. The precision in DI water was acceptable ranging from 8 to 38 % RSD. However, the precision in real environmental wastewaters could be poor, ranging from 15 to 120 % RSD, dependent upon unique matrix effects. In plasma, the overall recoveries of the EAPs were acceptable: 88 to 110 %, with %RSDs of 6 to 18 % (Table 3). The spiked recoveries of the TAM metabolites from plasma were good, ranging from 77 to 120 %, with %RSDs ranging from 27 to 32 %. Two of the TAM metabolites, 4- hydroxytamoxifen and n-desmethyl tamoxifen, were confirmed in most of the environmental aqueous samples. The discovery of TAM metabolites demonstrates that the source of the TAM metabolites, TAM, is constant, introducing a pseudo-persistence of this chemical into the environment.

  14. Magnetic recovery of modified activated carbon powder used for removal of endocrine disruptors present in water.

    PubMed

    Borghi, Chiara Caterina; Fabbri, Massimo

    2014-01-01

    This paper was aimed at studying sustainable solutions for the treatment of water polluted by octylphenols and nonylphenols that are xenoextrogen compounds affecting human health and dangerous for the aquatic environment. We studied the removal of 4-octylphenol and 4-n-nonylphenol with concentrations of the order of 5-10 mg/l on a laboratory scale. A mixing time of 10 min with 0.1 g/l of magnetic-activated carbons (MACs) was enough to obtain 95 +/- 5% adsorption of both 4-octylphenol and 4-n-nonylphenol. The adsorption of the surfactants IGEPAL CO-630 and TRITON X-100, which are precursors of branched 4-nonylphenol and the carcinogenic 4-tert-octylphenol, respectively, was also studied using the same technique. For concentrations between 2 and 10mg/l of these alkylphenols ethoxylated, after 10min mixing with 0.5 g/l of MACs, a 95 +/- 5% adsorption was obtained. A 97 +/- 1% removal of MACs was achieved after 10min of continuous-flow magnetic filtration (14.5 l/min). The filter used was made of SUS440C magnetic steel spheres. Srm-Co permanent magnets provided a uniform flux density field of about 500 mT. PMID:24645486

  15. Magnetic recovery of modified activated carbon powder used for removal of endocrine disruptors present in water.

    PubMed

    Borghi, Chiara Caterina; Fabbri, Massimo

    2014-01-01

    This paper was aimed at studying sustainable solutions for the treatment of water polluted by octylphenols and nonylphenols that are xenoextrogen compounds affecting human health and dangerous for the aquatic environment. We studied the removal of 4-octylphenol and 4-n-nonylphenol with concentrations of the order of 5-10 mg/l on a laboratory scale. A mixing time of 10 min with 0.1 g/l of magnetic-activated carbons (MACs) was enough to obtain 95 +/- 5% adsorption of both 4-octylphenol and 4-n-nonylphenol. The adsorption of the surfactants IGEPAL CO-630 and TRITON X-100, which are precursors of branched 4-nonylphenol and the carcinogenic 4-tert-octylphenol, respectively, was also studied using the same technique. For concentrations between 2 and 10mg/l of these alkylphenols ethoxylated, after 10min mixing with 0.5 g/l of MACs, a 95 +/- 5% adsorption was obtained. A 97 +/- 1% removal of MACs was achieved after 10min of continuous-flow magnetic filtration (14.5 l/min). The filter used was made of SUS440C magnetic steel spheres. Srm-Co permanent magnets provided a uniform flux density field of about 500 mT.

  16. Female reproductive activity and its endocrine correlates in the African lesser bushbaby, Galago moholi.

    PubMed

    Scheun, Juan; Nowack, Julia; Bennett, Nigel C; Ganswindt, Andre

    2016-02-01

    Steroid hormones play an important role in female reproductive physiology and behaviour and are often used to monitor important female reproductive events. However, such studies are often attempted on captive populations alone, delivering limited data. One such example is the African lesser bushbaby, Galago moholi, for which contradicting observational data exist between captive and free-ranging populations, while hormonal analyses have only been obtained from a single captive population. To extend and rectify the limited information, we monitored faecal progestagen and oestrogen metabolite levels across various important life history stages of both captive and free-ranging G. moholi. We additionally recorded changes in vaginal state as well as the occurrence of reproductive and aggressive behaviour throughout the study. Data from our captive population revealed an ovarian cycle length of 33.44 ± 0.59 days (mean ± SD), with follicular and luteal phases of 14.2 ± 1.0 and 19.1 ± 1.5 days, respectively, and an average pregnancy length of 128 ± 3.3 days. The initiation of female reproductive activity was closely linked to an oestrus-related increase in faecal oestrogen metabolite levels. Four of the seven captive females monitored in our study conceived during the May mating period, with one additional female fertilised in September, supporting the idea that the September mating period functions as a back-up for female G. moholi. Identified benchmark faecal progestagen metabolite levels (non-pregnant: >1 µg/g dry weight (DW), pregnant: >9 µg/g DW) should help researchers to determine pregnancy status of randomly wild-caught females in even a cross-sectional study setup. PMID:26649553

  17. Organic active materials for batteries

    DOEpatents

    Abouimrane, Ali; Weng, Wei; Amine, Khalil

    2016-08-16

    A rechargeable battery includes a compound having at least two active sites, R.sup.1 and R.sup.2; wherein the at least two active sites are interconnected by one or more conjugated moieties; each active site is coordinated to one or more metal ions M.sup.a+ or each active site is configured to coordinate to one or more metal ions; and "a" is 1, 2, or 3.

  18. Chronobiology in the endocrine system.

    PubMed

    Haus, Erhard

    2007-08-31

    Biological signaling occurs in a complex web with participation and interaction of the central nervous system, the autonomous nervous system, the endocrine glands, peripheral endocrine tissues including the intestinal tract and adipose tissue, and the immune system. All of these show an intricate time structure with rhythms and pulsatile variations in multiple frequencies. Circadian (about 24-hour) and circannual (about 1-year) rhythms are kept in step with the cyclic environmental surrounding by the timing and length of the daily light span. Rhythmicity of many endocrine variables is essential for their efficacy and, even in some instances, for the qualitative nature of their effects. Indeed, the continuous administration of certain hormones and their synthetic analogues may show substantially different effects than expected. In the design of drug-delivery systems and treatment schedules involving directly or indirectly the endocrine system, consideration of the human time organization is essential. A large amount of information on the endocrine time structure has accumulated, some of which is discussed in this review.

  19. Endocrine Glands & Their Hormones

    MedlinePlus

    ... Home » Cancer Registration & Surveillance Modules » Anatomy & Physiology » Endocrine System » Endocrine Glands & Their Hormones Cancer Registration & Surveillance Modules Anatomy & Physiology Intro to the Human Body Body Functions & Life Process Anatomical Terminology Review Quiz ...

  20. Endocrine system and obesity.

    PubMed

    Ashburn, Doyle D; Reed, Mary Jane

    2010-10-01

    Obesity is associated with significant alterations in endocrine function. An association with type 2 diabetes mellitus and dyslipidemia has been well documented. This article highlights the complexities of treating endocrine system disorders in obese patients.

  1. Multiple Endocrine Neoplasia Syndromes

    MedlinePlus

    ... or cancerous (malignant) tumors or grow excessively without forming tumors. Multiple endocrine neoplasia syndromes are caused by ... This Article Generic Name Select Brand Names corticotropin H.P. ACTHAR GEL epinephrine ADRENALIN Multiple Endocrine Neoplasia ...

  2. The heart is the center of a new endocrine, paracrine, and neuroendocrine system.

    PubMed

    Forssmann, W G; Nokihara, K; Gagelmann, M; Hock, D; Feller, S; Schulz-Knappe, P; Herbst, F

    1989-01-01

    This review indicates that the heart is a polypeptide-producing organ which should be classified among the traditional endocrine tissues. Cardiac hormones have only been known for a few years, the discovery of their endocrine functions, however, occurred in the 1950ies when Gauer, Henry and Kisch observed specific physiological and morphological features of the heart atria indicative of an endocrine activity. Because of their basic effects many target organs involved in the regulation of body fluid pressure and composition are related to this endocrine organ located in the atrial appendages of the heart. The compact endocrine portion of the heart is built up by myoendocrine cells which form the functional endocrine units and produce a variety of polypeptide hormones called cardiodilatin (CDD) or atrial natriuretic polypeptide (ANP), which belong to one family. Also, co-storage of a partially homologous regulatory polypeptide called brain natriuretic polypeptide (BNP) occurs, as has been determined by immunohistochemistry and radioimmunoassay. CDD and/or BNP are found in numerous organs where they exert paracrine and neurocrine functions, e.g., in the brain, peripheral nervous system, kidney, and adrenal medulla. In these organs, a differential post-translational processing of cardiac polypeptides is observed, resulting in different functional activities according to discriminating receptor interactions and degrading metabolism. Some of the extra-auricular sites of synthesis and storage of CDD-like peptides are briefly mentioned. In summary the heart constitutes the center of a multilocal and multifunctional system of specific cardiac polypeptides of endocrine, paraneuronal, and neuronal character.

  3. Designing Endocrine Disruption Out of the Next Generation of Chemicals

    PubMed Central

    Schug, T.T; Abagyan, R.; Blumberg, B.; Collins, T.J.; Crews, D.; DeFur, P.L.; Dickerson, S.M.; Edwards, T.M.; Gore, A.C.; Guillette, L.J.; Hayes, T.; Heindel, J.J.; Moores, A.; Patisaul, H.B.; Tal, T.L.; Thayer, K.A.; Vandenberg, L.N.; Warner, J.; Watson, C.S.; Saal, F.S. vom; Zoeller, R.T.; O’Brien, K.P.; Myers, J.P.

    2013-01-01

    A central goal of green chemistry is to avoid hazard in the design of new chemicals. This objective is best achieved when information about a chemical’s potential hazardous effects is obtained as early in the design process as feasible. Endocrine disruption is a type of hazard that to date has been inadequately addressed by both industrial and regulatory science. To aid chemists in avoiding this hazard, we propose an endocrine disruption testing protocol for use by chemists in the design of new chemicals. The Tiered Protocol for Endocrine Disruption (TiPED) has been created under the oversight of a scientific advisory committee composed of leading representatives from both green chemistry and the environmental health sciences. TiPED is conceived as a tool for new chemical design, thus it starts with a chemist theoretically at “the drawing board.” It consists of five testing tiers ranging from broad in silico evaluation up through specific cell- and whole organism-based assays. To be effective at detecting endocrine disruption, a testing protocol must be able to measure potential hormone-like or hormone-inhibiting effects of chemicals, as well as the many possible interactions and signaling sequellae such chemicals may have with cell-based receptors. Accordingly, we have designed this protocol to broadly interrogate the endocrine system. The proposed protocol will not detect all possible mechanisms of endocrine disruption, because scientific understanding of these phenomena is advancing rapidly. To ensure that the protocol remains current, we have established a plan for incorporating new assays into the protocol as the science advances. In this paper we present the principles that should guide the science of testing new chemicals for endocrine disruption, as well as principles by which to evaluate individual assays for applicability, and laboratories for reliability. In a ‘proof-of-principle’ test, we ran 6 endocrine disrupting chemicals (EDCs) that act

  4. CtBP and associated LSD1 are required for transcriptional activation by NeuroD1 in gastrointestinal endocrine cells.

    PubMed

    Ray, Subir K; Li, H Joyce; Metzger, Eric; Schüle, Roland; Leiter, Andrew B

    2014-06-01

    Gene expression programs required for differentiation depend on both DNA-bound transcription factors and surrounding histone modifications. Expression of the basic helix-loop-helix (bHLH) protein NeuroD1 is restricted to endocrine cells in the gastrointestinal (GI) tract, where it is important for endocrine differentiation. RREB1 (RAS-responsive element binding protein 1), identified as a component of the CtBP corepressor complex, binds to nearby DNA elements to associate with NeuroD and potentiate transcription of a NeuroD1 target gene. Transcriptional activation by RREB1 depends on recruitment of CtBP with its associated proteins, including LSD1, through its PXDLS motifs. The mechanism of transcriptional activation by CtBP has not been previously characterized. Here we found that activation was dependent on the histone H3 lysine 9 (H3K9) demethylase activity of LSD1, which removes repressive methyl marks from dimethylated H3K9 (H3K9Me2), to facilitate subsequent H3K9 acetylation by the NeuroD1-associated histone acetyltransferase, P300/CBP-associated factor (PCAF). The secretin, β-glucokinase, insulin I, and insulin II genes, four known direct targets of NeuroD1 in intestinal and pancreatic endocrine cells, all show similar promoter occupancy by CtBP-associated proteins and PCAF, with acetylation of H3K9. This work may indicate a mechanism for selective regulation of transcription by CtBP and LSD1 involving their association with specific transcription factors and cofactors to drive tissue-specific transcription.

  5. Genetic testing by cancer site: endocrine system.

    PubMed

    Pilarski, Robert; Nagy, Rebecca

    2012-01-01

    Numerous hereditary syndromes, caused by mutations in multiple tumor suppressor genes and oncogenes, can cause tumors in organs of the endocrine system. The primary syndromes (and genes) addressed here include multiple endocrine neoplasia types 1 and 2 (MEN1 and RET genes), Cowden syndrome (PTEN), hereditary pheochromocytoma/paraganglioma syndromes (multiple genes), and von Hippel-Lindau disease (VHL). Clinical genetic testing is available for each of these syndromes and is generally directed to individuals with endocrine or other tumors and additional features suggestive of a hereditary syndrome. However, for some endocrine tumors, the proportion because of heredity is so high that genetic testing may be appropriate for all affected individuals. Management for hereditary cases typically involves aggressive screening and/or surgical protocols, starting at young ages to minimize morbidity and mortality. Endocrine tumors can be less commonly seen in a number of other hereditary syndromes (eg, neurofibromatosis), which are not reviewed in this section.

  6. Endocrine disruption in aquatic vertebrates.

    PubMed

    Kloas, Werner; Urbatzka, Ralph; Opitz, Robert; Würtz, Sven; Behrends, Thomas; Hermelink, Björn; Hofmann, Frauke; Jagnytsch, Oana; Kroupova, Hana; Lorenz, Claudia; Neumann, Nadja; Pietsch, Constanze; Trubiroha, Achim; Van Ballegooy, Christoph; Wiedemann, Caterina; Lutz, Ilka

    2009-04-01

    Environmental compounds can interfere with endocrine systems of wildlife and humans. The main sink of such substances, called endocrine disrupters (ED), are surface waters. Thus, aquatic vertebrates, such as fish and amphibians, are most endangered. ED can adversely affect reproductive biology and the thyroid system. ED act by (anti)estrogenic and (anti)androgenic modes of action, resulting in abnormal sexual differentiation and impaired reproduction. These effects are mainly driven by direct interferences of ED with sex steroid receptors rather than indirectly by impacting synthesis and bioavailability of sex steroids, which in turn might affect the hypothalamic-pituitary-gonadal axis. Recent findings reveal that, in addition to the human-produced waste of ED, natural sources, such as parasites and decomposition of leaves, also might act as ED, markedly affecting sexual differentiation and reproduction in fish and amphibians. Although the thyroid system has essential functions in both fish and amphibians, amphibian metamorphosis has been introduced as the most sensitive model to detect thyroidal ED; no suitable fish model exists. Whereas ED may act primarily on only one specific endocrine target, all endocrine systems will eventually be deregulated as they are intimately connected to each other. The recent ecotoxicological issue of pharmaceutically active compounds (PhACs) present in the aquatic environment indicates a high potential for further endocrine modes of action on aquatic vertebrates by ED derived from PhACs, such as glucocorticoids, progestins, and beta-agonists.

  7. 78 FR 57859 - Draft Guidance for Industry on Endocrine Disruption Potential of Drugs: Nonclinical Evaluation...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-20

    ... determine the potential for a drug to disrupt the endocrine system. This draft guidance also discusses... compounds that have the potential to interfere with some aspect of the endocrine system of an organism or its progeny. Any component of the endocrine system can be a target of endocrine disruptors,...

  8. [Endocrine tumors of the testis].

    PubMed

    Loy, V; Linke, J

    2003-07-01

    The most characteristic endocrine tumours of the testis are germ cell tumours and sex cord/gonadal stromal tumours. They include the primary carcinoid, the relation of which to teratomas is still unclear. In general, gonadal stromal tumours are rare, however, endocrine activity occurs in at least 10%-20%. Among gonadal stromal tumours, only Leydig cell tumours and Sertoli cell tumours are of practical importance. Endocrine disorders are mostly related to Leydig cell tumours (gynaecomastia, pubertas praecox). Although less frequent than the other gonadal stromal tumours, they can, in principle, occur. The large cell calcifying Sertoli cell tumour occurs in association with other complex disorders (i.e. Peutz-Jeghers syndrome). Valuable markers are: inhibin, calretinin, cytokeratin, melan-A, CD-99, Ki-67, androgen receptor and p53. As the conventional morphology and immunohistological markers frequently overlap, unclear cases should be referred to specialised centres. PMID:14513279

  9. [Regeneration of endocrine gastroenteropancreatic system in experimental and clinical pathology: concept development and current problems].

    PubMed

    Ivanova, V F

    2013-01-01

    Literature review contains the literature data and the results of author's own investigations describing the coming into being and the development of the concepts on the regeneration of endocrine gastroenteropancreatic (GEP) system under the conditions of norm, experimental and clinical pathology. Data analysis permitted to reveal the similarities and differences in the course of this process in various organs of the digestive system. Endocrine GEP system renewal occurs at different levels of its organization. At the tissue level, the endocrine cells renewal occurs via the transformation of exocrine cells into the endocrine ones and as a result of differentiation from stem cells via the "agranular" cell stage which are precursors of the endocrine cells. This pathway of regeneration is the major one after the damage. Regeneration at cellular level occurs through mitotic division of the differentiated endocrine cells (early stage of regeneration) and as a result of the formation granules with different hormonal profile in D-cells. At the intracellular level, the regeneration is realized through the intracellular structure restoration after their damage induced by the increase of cell functional activity accompanied by degranulation and dystrophic changes development

  10. Endocrine effects of marijuana.

    PubMed

    Brown, Todd T; Dobs, Adrian S

    2002-11-01

    In the 35 years since the active compound of marijuana, delta9-tetrahydrocannabinol, was isolated, the psychological and physiological impact of marijuana use has been actively investigated. Animal models have demonstrated that cannabinoid administration acutely alters multiple hormonal systems, including the suppression of the gonadal steroids, growth hormone, prolactin, and thyroid hormone and the activation of the hypothalamic-pituitary-adrenal axis. These effects are mediated by binding to the endogenous cannabinoid receptor in or near the hypothalamus. Despite these findings in animals, the effects in humans have been inconsistent, and discrepancies are likely due in part to the development of tolerance. The long-term consequences of marijuana use in humans on endocrine systems remain unclear.

  11. Endocrine dysfunction in sepsis: a beneficial or deleterious host response?

    PubMed

    Gheorghiţă, Valeriu; Barbu, Alina Elena; Gheorghiu, Monica Livia; Căruntu, Florin Alexandru

    2015-03-01

    Sepsis is a systemic, deleterious inflammatory host response triggered by an infective agent leading to severe sepsis, septic shock and multi-organ failure. The host response to infection involves a complex, organized and coherent interaction between immune, autonomic, neuroendocrine and behavioral systems. Recent data have confirmed that disturbances of the autonomic nervous and neuroendocrine systems could contribute to sepsis-induced organ dysfunction. Through this review, we aimed to summarize the current knowledge about the endocrine dysfunction as response to sepsis, specifically addressed to vasopressin, copeptin, cortisol, insulin and leptin. We searched the following readily accessible, clinically relevant databases: PubMed, UpToDate, BioMed Central. The immune system could be regarded as a "diffuse sensory organ" that signals the presence of pathogens to the brain through different pathways, such as the vagus nerve, endothelial activation/dysfunction, cytokines and neurotoxic mediators and the circumventricular organs, especially the neurohypophysis. The hormonal profile changes substantially as a consequence of inflammatory mediators and microorganism products leading to inappropriately low levels of vasopressin, sick euthyroid syndrome, reduced adrenal responsiveness to ACTH, insulin resistance, hyperglycemia as well as hyperleptinemia. In conclusion, clinical diagnosis of this "pan-endocrine illness" is frequently challenging due to the many limiting factors. The most important benefits of endocrine markers in the management of sepsis may be reflected by their potential to be used as biomarkers in different scoring systems to estimate the severity of the disease and the risk of death.

  12. Tracking multiple modes of endocrine activity in Australia's largest inland sewage treatment plant and effluent- receiving environment using a panel of in vitro bioassays.

    PubMed

    Roberts, Jenna; Bain, Peter A; Kumar, Anupama; Hepplewhite, Christopher; Ellis, David J; Christy, Andrew G; Beavis, Sara G

    2015-10-01

    Estrogenicity of sewage effluents, and related ecotoxicological effects in effluent-receiving environments, have been widely reported over the last 2 decades. However, relatively little attention has been given to other endocrine pathways that may be similarly disrupted by a growing list of contaminants of concern. Furthermore, the Australian evidence base is limited compared with those of Europe and North America. During a low dilution period in summer, the authors investigated multiple endocrine potencies in Australia's largest inland sewage treatment plant (STP) and the Lower Molonglo/Upper Murrumbidgee effluent-receiving environment. This STP receives 900 L/s of mostly domestic wastewater from a population of 350 000, and contributes a high proportion of total flow in the lower catchment during dry periods. A panel of in vitro receptor-driven transactivation assays were used to detect (anti)estrogenic, (anti) androgenic, (anti)progestagenic, glucocorticoid, and peroxisome-proliferator activity at various stages of the sewage treatment process. Total estrogenic and (anti)androgenic potency was removed after primary and/or secondary treatment; however, total removal efficiency for glucocorticoid potency was poorer (53-66%), and progestagenic potency was found to increase along the treatment train. Estrogenicity was detected in surface waters and bed sediments upstream and downstream of the effluent outfall, at maximum levels 10 times lower than low-hazard thresholds. Glucocorticoid and progestagenic activity were found to persist to 4 km downstream of the effluent outfall, suggesting that future research is needed on these endocrine-disrupting chemical categories in effluent-receiving systems. PMID:25939690

  13. Tracking multiple modes of endocrine activity in Australia's largest inland sewage treatment plant and effluent- receiving environment using a panel of in vitro bioassays.

    PubMed

    Roberts, Jenna; Bain, Peter A; Kumar, Anupama; Hepplewhite, Christopher; Ellis, David J; Christy, Andrew G; Beavis, Sara G

    2015-10-01

    Estrogenicity of sewage effluents, and related ecotoxicological effects in effluent-receiving environments, have been widely reported over the last 2 decades. However, relatively little attention has been given to other endocrine pathways that may be similarly disrupted by a growing list of contaminants of concern. Furthermore, the Australian evidence base is limited compared with those of Europe and North America. During a low dilution period in summer, the authors investigated multiple endocrine potencies in Australia's largest inland sewage treatment plant (STP) and the Lower Molonglo/Upper Murrumbidgee effluent-receiving environment. This STP receives 900 L/s of mostly domestic wastewater from a population of 350 000, and contributes a high proportion of total flow in the lower catchment during dry periods. A panel of in vitro receptor-driven transactivation assays were used to detect (anti)estrogenic, (anti) androgenic, (anti)progestagenic, glucocorticoid, and peroxisome-proliferator activity at various stages of the sewage treatment process. Total estrogenic and (anti)androgenic potency was removed after primary and/or secondary treatment; however, total removal efficiency for glucocorticoid potency was poorer (53-66%), and progestagenic potency was found to increase along the treatment train. Estrogenicity was detected in surface waters and bed sediments upstream and downstream of the effluent outfall, at maximum levels 10 times lower than low-hazard thresholds. Glucocorticoid and progestagenic activity were found to persist to 4 km downstream of the effluent outfall, suggesting that future research is needed on these endocrine-disrupting chemical categories in effluent-receiving systems.

  14. The Organic Puppet Theatre. Health Activities Book.

    ERIC Educational Resources Information Center

    Schultz, Terry Louis; Sorenson, Linda M.

    The Organic Puppet Theatre is a creative medium for the classroom, home, day care center, hospital, community center, and clinic. It is designed for children in the early elementary years. The objective of the activity is to acquaint children with the functions of the various organs of the body, how they interact, and how they are affected by poor…

  15. [Endocrine functions of the brain in adult and developing mammals].

    PubMed

    Ugriumov, M V

    2009-01-01

    The main prerequisite for organism's viability is the maintenance of the internal environment despite changes in the external environment, which is provided by the neuroendocrine control system. The key unit in this system is hypothalamus exerting endocrine effects on certain peripheral organs and anterior pituitary. Physiologically active substances of neuronal origin enter blood vessels in the neurohemal parts of hypothalamus where no blood-brain barrier exists. In other parts of the adult brain, the arrival of physiologically active substances is blocked by the blood-brain barrier. According to the generally accepted concept, the neuroendocrine system formation in ontogeny starts with the maturation of peripheral endocrine glands, which initially function autonomously and then are controlled by the anterior pituitary. The brain is engaged in neuroendocrine control after its maturation completes, which results in a closed control system typical of adult mammals. Since neurons start to secrete physiologically active substances soon after their formation and long before interneuronal connections are formed, these cells are thought to have an effect on brain development as inducers. Considering that there is no blood-brain barrier during this period, we proposed the hypothesis that the developing brain functions as a multipotent endocrine organ. This means that tens of physiologically active substances arrive from the brain to the systemic circulation and have an endocrine effect on the whole body development. Dopamine, serotonin, and gonadotropin-releasing hormone were selected as marker physiologically active substances of cerebral origin to test this hypothesis. In adult animals, they act as neurotransmitters or neuromodulators transmitting information from neuron to neuron as well as neurohormones arriving from the hypothalamus with portal blood to the anterior pituitary. Perinatal rats--before the blood-brain barrier is formed--proved to have equally high

  16. Endocrine scintigraphy with hybrid SPECT/CT.

    PubMed

    Wong, Ka Kit; Fig, Lorraine M; Youssef, Ehab; Ferretti, Alice; Rubello, Domenico; Gross, Milton D

    2014-10-01

    Nuclear medicine imaging of endocrine disorders takes advantage of unique cellular properties of endocrine organs and tissues that can be depicted by targeted radiopharmaceuticals. Detailed functional maps of biodistributions of radiopharmaceutical uptake can be displayed in three-dimensional tomographic formats, using single photon emission computed tomography (CT) that can now be directly combined with simultaneously acquired cross-sectional anatomic maps derived from CT. The integration of function depicted by scintigraphy and anatomy with CT has synergistically improved the efficacy of nuclear medicine imaging across a broad spectrum of clinical applications, which include some of the oldest imaging studies of endocrine dysfunction.

  17. Endocrine FGFs: Evolution, Physiology, Pathophysiology, and Pharmacotherapy

    PubMed Central

    Itoh, Nobuyuki; Ohta, Hiroya; Konishi, Morichika

    2015-01-01

    The human fibroblast growth factor (FGF) family comprises 22 structurally related polypeptides that play crucial roles in neuronal functions, development, and metabolism. FGFs are classified as intracrine, paracrine, and endocrine FGFs based on their action mechanisms. Paracrine and endocrine FGFs are secreted signaling molecules by acting via cell-surface FGF receptors (FGFRs). Paracrine FGFs require heparan sulfate as a cofactor for FGFRs. In contrast, endocrine FGFs, comprising FGF19, FGF21, and FGF23, require α-Klotho or β-Klotho as a cofactor for FGFRs. Endocrine FGFs, which are specific to vertebrates, lost heparan sulfate-binding affinity and acquired a systemic signaling system with α-Klotho or β-Klotho during early vertebrate evolution. The phenotypes of endocrine FGF knockout mice indicate that they play roles in metabolism including bile acid, energy, and phosphate/active vitamin D metabolism. Accumulated evidence for the involvement of endocrine FGFs in human genetic and metabolic diseases also indicates their pathophysiological roles in metabolic diseases, potential risk factors for metabolic diseases, and useful biomarkers for metabolic diseases. The therapeutic utility of endocrine FGFs is currently being developed. These findings provide new insights into the physiological and pathophysiological roles of endocrine FGFs and potential diagnostic and therapeutic strategies for metabolic diseases. PMID:26483756

  18. GATA factors in endocrine neoplasia.

    PubMed

    Pihlajoki, Marjut; Färkkilä, Anniina; Soini, Tea; Heikinheimo, Markku; Wilson, David B

    2016-02-01

    GATA transcription factors are structurally-related zinc finger proteins that recognize the consensus DNA sequence WGATAA (the GATA motif), an essential cis-acting element in the promoters and enhancers of many genes. These transcription factors regulate cell fate specification and differentiation in a wide array of tissues. As demonstrated by genetic analyses of mice and humans, GATA factors play pivotal roles in the development, homeostasis, and function of several endocrine organs including the adrenal cortex, ovary, pancreas, parathyroid, pituitary, and testis. Additionally, GATA factors have been shown to be mutated, overexpressed, or underexpressed in a variety of endocrine tumors (e.g., adrenocortical neoplasms, parathyroid tumors, pituitary adenomas, and sex cord stromal tumors). Emerging evidence suggests that GATA factors play a direct role in the initiation, proliferation, or propagation of certain endocrine tumors via modulation of key developmental signaling pathways implicated in oncogenesis, such as the WNT/β-catenin and TGFβ pathways. Altered expression or function of GATA factors can also affect the metabolism, ploidy, and invasiveness of tumor cells. This article provides an overview of the role of GATA factors in endocrine neoplasms. Relevant animal models are highlighted.

  19. Steroidal hormones and other endocrine active compounds in shallow groundwater in nonagricultural areas of Minnesota—Study design, methods, and data, 2009–10

    USGS Publications Warehouse

    Erickson, Melinda L.

    2012-01-01

    The U.S. Geological Survey, in cooperation with the Minnesota Pollution Control Agency, completed a study on the occurrence of steroidal hormones and other endocrine active compounds in shallow groundwater in nonagricultural areas of Minnesota during 2009–10. This report describes the study design and methods, and presents the data collected on steroidal hormones and other related compounds. Environmental and quality-control samples were collected from 40 wells as part of this study. Samples were analyzed by the U.S. Geological Survey National Water Quality Laboratory for 16 steroidal hormones and 4 other related compounds, of which all but 2 compounds are endocrine active compounds. Most of the water samples did not contain detectable concentrations of any of the 20 compounds analyzed. Water samples from three wells had detectable concentrations of one or more compounds. Bisphenol A was detected in samples from three wells, and trans-diethylstilbestrol was detected in one of the samples in which bisphenol A also was detected.

  20. Estrogen receptor alpha somatic mutations Y537S and D538G confer breast cancer endocrine resistance by stabilizing the activating function-2 binding conformation

    PubMed Central

    Fanning, Sean W; Mayne, Christopher G; Dharmarajan, Venkatasubramanian; Carlson, Kathryn E; Martin, Teresa A; Novick, Scott J; Toy, Weiyi; Green, Bradley; Panchamukhi, Srinivas; Katzenellenbogen, Benita S; Tajkhorshid, Emad; Griffin, Patrick R; Shen, Yang; Chandarlapaty, Sarat; Katzenellenbogen, John A; Greene, Geoffrey L

    2016-01-01

    Somatic mutations in the estrogen receptor alpha (ERα) gene (ESR1), especially Y537S and D538G, have been linked to acquired resistance to endocrine therapies. Cell-based studies demonstrated that these mutants confer ERα constitutive activity and antiestrogen resistance and suggest that ligand-binding domain dysfunction leads to endocrine therapy resistance. Here, we integrate biophysical and structural biology data to reveal how these mutations lead to a constitutively active and antiestrogen-resistant ERα. We show that these mutant ERs recruit coactivator in the absence of hormone while their affinities for estrogen agonist (estradiol) and antagonist (4-hydroxytamoxifen) are reduced. Further, they confer antiestrogen resistance by altering the conformational dynamics of the loop connecting Helix 11 and Helix 12 in the ligand-binding domain of ERα, which leads to a stabilized agonist state and an altered antagonist state that resists inhibition. DOI: http://dx.doi.org/10.7554/eLife.12792.001 PMID:26836308

  1. Circadian rhythms and endocrine functions in adult insects.

    PubMed

    Bloch, Guy; Hazan, Esther; Rafaeli, Ada

    2013-01-01

    Many behavioral and physiological processes in adult insects are influenced by both the endocrine and circadian systems, suggesting that these two key physiological systems interact. We reviewed the literature and found that experiments explicitly testing these interactions in adult insects have only been conducted for a few species. There is a shortage of measurements of hormone titers throughout the day under constant conditions even for the juvenile hormones (JHs) and ecdysteroids, the best studied insect hormones. Nevertheless, the available measurements of hormone titers coupled with indirect evidence for circadian modulation of hormone biosynthesis rate, and the expression of genes encoding proteins involved in hormone biosynthesis, binding or degradation are consistent with the hypothesis that the circulating levels of many insect hormones are influenced by the circadian system. Whole genome microarray studies suggest that the modulation of farnesol oxidase levels is important for the circadian regulation of JH biosynthesis in honey bees, mosquitoes, and fruit flies. Several studies have begun to address the functional significance of circadian oscillations in endocrine signaling. The best understood system is the circadian regulation of Pheromone Biosynthesis Activating Neuropeptide (PBAN) titers which is important for the temporal organization of sexual behavior in female moths. The evidence that the circadian and endocrine systems interact has important implications for studies of insect physiology and behavior. Additional studies on diverse species and physiological processes are needed for identifying basic principles underlying the interactions between the circadian and endocrine systems in insects.

  2. Endocrine and metabolic emergencies: thyroid storm

    PubMed Central

    Carroll, Richard; Matfin, Glenn

    2010-01-01

    Thyrotoxicosis is a common endocrine condition that may be secondary to a number of underlying processes. Thyroid storm (also known as thyroid or thyrotoxic crisis) represents the severe end of the spectrum of thyrotoxicosis and is characterized by compromised organ function. Whilst rare in the modern era, the mortality rate remains high, and prompt consideration of this endocrine emergency, with specific treatments, can improve outcomes. PMID:23148158

  3. Male endocrine dysfunction.

    PubMed

    Hotaling, James M; Patel, Zamip

    2014-02-01

    Evaluation for endocrine function is a pivotal part of the male infertility workup. Endocrine dysfunction may result from endogenous and exogenous sources. This article describes the traditional roles that the hypothalamic-pituitary-gonadal endocrine axis plays in spermatogenesis and testicular dysfunction, as well as other insults that may contribute to hypospermatogenesis. Recent research into the role alternative hormonal axes play in spermatogenesis and promising new technologies that may correct inborn or acquired endocrinopathies leading to impaired sperm growth and maturation are discussed.

  4. Adrenocortical endocrine disruption.

    PubMed

    Harvey, Philip W

    2016-01-01

    The adrenal has been neglected in endocrine disruption regulatory testing strategy. The adrenal is a vital organ, adrenocortical insufficiency is recognised in life threatening "adrenal crises" and Addison's disease, and the consequences of off-target toxicological inhibition of adrenocortical steroidogenesis is well recognised in clinical medicine, where drugs such as aminoglutethimide and etomidate killed patients via unrecognised inhibition of adrenocortical steroidogenic enzymes (e.g. CYP11B1) along the cortisol and aldosterone pathways. The consequences of adrenocortical dysfunction during early development are also recognised in the congenital salt wasting and adrenogenital syndromes presenting neonatally, yet despite a remit to focus on developmental and reproductive toxicity mechanisms of endocrine disruption by many regulatory agencies (USEPA EDSTAC; REACH) the assessment of adrenocortical function has largely been ignored. Further, every step in the adrenocortical steroidogenic pathway (ACTH receptor, StAR, CYP's 11A1, 17, 21, 11B1, 11B2, and 3-hydroxysteroid dehydrogenase Δ4,5 isomerase) is known to be a potential target with multiple examples of chemicals inhibiting these targets. Many of these chemicals have been detected in human and wildlife tissues. This raises the question of whether exposure to low level environmental chemicals may be affecting adrenocortical function. This review examines the omission of adrenocortical testing in the current regulatory frameworks; the characteristics that make the adrenal cortex particularly vulnerable to toxic insult; chemicals and their toxicological targets within the adrenocortical steroidogenic pathways; the typical manifestations of adrenocortical toxicity (e.g. human iatrogenically induced pharmacotoxicological adrenal insufficiency, manifestations in typical mammalian regulatory general toxicology studies, manifestations in wildlife) and models of adrenocortical functional assessment. The utility of the

  5. Performance of metal-organic framework MIL-101 after surfactant modification in the extraction of endocrine disrupting chemicals from environmental water samples.

    PubMed

    Huang, Zhenzhen; Lee, Hian Kee

    2015-10-01

    The research presented in this paper explored the modification and application of a metal-organic framework, MIL-101, with nonionic surfactant-Triton X-114 in dispersive solid-phase extraction for the preconcentration of four endocrine disrupting chemicals (estrone, 17α-ethynylestradiol, estriol and diethylstilbestrol) from environmental water samples. Triton X-114 molecules could be adsorbed by the hydrophobic surface of the MIL-101 crystals, and thus improved the dispersibility of MIL-101 in aqueous solution by serving as a hydrophilic coating. Cloud point phase separation from Triton X-114 accelerated the separation of extracts from the aqueous matrix. The proposed method combines the favorable attributes of strong adsorption capacity resulting from the porous structure of MIL-101 and self-assembly of Triton X-114 molecules. Post-extraction derivatization using N-methyl-N-(trimethylsilyl)trifluoroacetamide was employed to facilitate the quantitative determination of the extracts by gas chromatography-mass spectrometry. The main factors affecting the preparation of modified MIL-101, and extraction of the analytes, such as the amount of surfactant, the ultrasonic and vortex durations, solution pH and desorption conditions, were investigated in detail. Under the optimized conditions, the present method yielded low limits of detection (0.006-0.023 ng/mL), good linearity from 0.09 to 45 ng/mL (coefficients of determination higher than 0.9980) and acceptable precision (relative standard deviations of 2.2-13%). The surface modified MIL-101 was demonstrated to be effective for the extraction of the selected estrogens from aqueous samples, giving rise to markedly improved extraction performance compared to the unmodified MIL-101. PMID:26078172

  6. Performance of metal-organic framework MIL-101 after surfactant modification in the extraction of endocrine disrupting chemicals from environmental water samples.

    PubMed

    Huang, Zhenzhen; Lee, Hian Kee

    2015-10-01

    The research presented in this paper explored the modification and application of a metal-organic framework, MIL-101, with nonionic surfactant-Triton X-114 in dispersive solid-phase extraction for the preconcentration of four endocrine disrupting chemicals (estrone, 17α-ethynylestradiol, estriol and diethylstilbestrol) from environmental water samples. Triton X-114 molecules could be adsorbed by the hydrophobic surface of the MIL-101 crystals, and thus improved the dispersibility of MIL-101 in aqueous solution by serving as a hydrophilic coating. Cloud point phase separation from Triton X-114 accelerated the separation of extracts from the aqueous matrix. The proposed method combines the favorable attributes of strong adsorption capacity resulting from the porous structure of MIL-101 and self-assembly of Triton X-114 molecules. Post-extraction derivatization using N-methyl-N-(trimethylsilyl)trifluoroacetamide was employed to facilitate the quantitative determination of the extracts by gas chromatography-mass spectrometry. The main factors affecting the preparation of modified MIL-101, and extraction of the analytes, such as the amount of surfactant, the ultrasonic and vortex durations, solution pH and desorption conditions, were investigated in detail. Under the optimized conditions, the present method yielded low limits of detection (0.006-0.023 ng/mL), good linearity from 0.09 to 45 ng/mL (coefficients of determination higher than 0.9980) and acceptable precision (relative standard deviations of 2.2-13%). The surface modified MIL-101 was demonstrated to be effective for the extraction of the selected estrogens from aqueous samples, giving rise to markedly improved extraction performance compared to the unmodified MIL-101.

  7. Organic solvent regeneration of granular activated carbon

    NASA Astrophysics Data System (ADS)

    Cross, W. H.; Suidan, M. T.; Roller, M. A.; Kim, B. R.; Gould, J. P.

    1982-09-01

    The use of activated carbon for the treatment of industrial waste-streams was shown to be an effective treatment. The high costs associated with the replacement or thermal regeneration of the carbon have prohibited the economic feasibility of this process. The in situ solvent regeneration of activated carbon by means of organic solvent extraction was suggested as an economically alternative to thermal regeneration. The important aspects of the solvent regeneration process include: the physical and chemical characteristics of the adsorbent, the pore size distribution and energy of adsorption associated with the activated carbon; the degree of solubility of the adsorbate in the organic solvent; the miscibility of the organic solvent in water; and the temperature at which the generation is performed.

  8. Sleep and the Endocrine System.

    PubMed

    Morgan, Dionne; Tsai, Sheila C

    2016-03-01

    In this article, the effect of sleep and sleep disorders on endocrine function and the influence of endocrine abnormalities on sleep are discussed. Sleep disruption and its associated endocrine consequences in the critically ill patient are also reviewed. PMID:26972038

  9. Sleep and the Endocrine System.

    PubMed

    Morgan, Dionne; Tsai, Sheila C

    2016-03-01

    In this article, the effect of sleep and sleep disorders on endocrine function and the influence of endocrine abnormalities on sleep are discussed. Sleep disruption and its associated endocrine consequences in the critically ill patient are also reviewed.

  10. Sleep and the endocrine system.

    PubMed

    Morgan, Dionne; Tsai, Sheila C

    2015-07-01

    In this article, the effect of sleep and sleep disorders on endocrine function and the influence of endocrine abnormalities on sleep are discussed. Sleep disruption and its associated endocrine consequences in the critically ill patient are also reviewed.

  11. Phosphofructokinase Activities in Photosynthetic Organisms 1

    PubMed Central

    Carnal, Nancy Wieland; Black, Clanton C.

    1983-01-01

    A pyrophosphate-dependent phosphofructokinase (PPi-PFK) activity is detectable in extracts of a wide variety of primitive and advanced plants, the Charalean algae, and in the photosynthetic bacterium, Rhodospirillum rubrum. Angiosperms with extractable PPi-PFK activities 4- to 70-fold higher than the respective ATP-PFK activities tend to be succulent and to exhibit CAM. Even though PPi-PFK activity is not detected in crude extracts of some well known CAM plants, e.g. plants in the Crassulaceae, gel filtration of the extract and/or inclusion of the PPi-PFK activator, fructose 2,6-bisphosphate, in the assay reveals that a PPi-PFK activity is present in these species. Fructose 2,6-bisphosphate likewise activates PPi-PFK activities in extracts of C3 and C4 plants. C3 and C4 plant PPi-PFK activities are roughly equivalent to ATP-PFK activities in the same species. PPi-PFK activity is also detected in some bryophytes, lower vascular plants, ferns, and gymnosperms. The Charophytes, advanced algae presumed to be similar to species ancestral to vascular plants, exhibit at least 4-fold higher PPi-PFK than ATP-PFK activities. R. rubrum also exhibits a much higher PPi-PFK activity than ATP-PFK activity. These data indicate that PPi-PFK may serve as an alternate enzyme to ATP-PFK in glycolysis in a wide range of photosynthetic organisms. PMID:16662776

  12. The endocrine quiz

    PubMed Central

    Kalra, Sanjay; Baruah, Manash P.; Nagesh, V. Sri

    2014-01-01

    With the recent explosion in endocrine conferences, audience fatigue has set in and conference planners are now looking at newer pedagogic methods to revive the interest of audiences in these conferences. The endocrine quiz has finally come of vogue and is increasingly becoming one of the most popular attractions of any ranking endocrine conference. The endocrine quiz has a large and varied palette and draws questions from religious scriptures, history, literature, current affairs, sports, movies and basic and paramedical sciences. The more we delve into the quizzable aspects of endocrinology, the more we realize that endocrinology is ubiquitous and there is no sphere in human life untouched by endocrine disorders. Be it epic characters like Kumbhakarna and Bheema, fiction characters like Tintin or Orphan Annie, sportspersons like Gail Devers or heads of state like George Bush Sr and Boris Yeltsin, all have contributed to the melting pot of endocrine quizzing. Adding further grist to the endocrine mill are the Nobel prizes, with their attendant anecdotes and controversies. Step into this world of endocrine quizzing to have an up close and personal look at the diverse facets of this subject. PMID:24944922

  13. Endocrine diseases of rodents.

    PubMed

    Collins, Bobby R

    2008-01-01

    The frequency of documented endocrine diseases in rodents and other small mammals varies considerably among the species maintained as pets, biomedical research animals, or display animals in zoos. The clinical diagnosis of endocrine diseases almost never occurs in free-ranging animals in their native habitat. Feral animals that have clinical endocrine disease, such as neoplasia, adrenal cortical hyperplasia, or diabetes, would exhibit clinical signs of altered behavior that would result in their removal by predators. The diagnosis of endocrine disease thus takes place in the relatively protective environment of captivity. This observation should forewarn pet owners and clinicians caring for these animals that the environment contributes to the development of endocrine diseases in these animals.

  14. Surface-active organics in atmospheric aerosols.

    PubMed

    McNeill, V Faye; Sareen, Neha; Schwier, Allison N

    2014-01-01

    Surface-active organic material is a key component of atmospheric aerosols. The presence of surfactants can influence aerosol heterogeneous chemistry, cloud formation, and ice nucleation. We review the current state of the science on the sources, properties, and impacts of surfactants in atmospheric aerosols. PMID:23408277

  15. Human biological monitoring of suspected endocrine-disrupting compounds

    PubMed Central

    Faniband, Moosa; Lindh, Christian H; Jönsson, Bo AG

    2014-01-01

    Endocrine-disrupting compounds are exogenous agents that interfere with the natural hormones of the body. Human biological monitoring is a powerful method for monitoring exposure to endocrine disrupting compounds. In this review, we describe human biological monitoring systems for different groups of endocrine disrupting compounds, polychlorinated biphenyls, brominated flame retardants, phthalates, alkylphenols, pesticides, metals, perfluronated compounds, parabens, ultraviolet filters, and organic solvents. The aspects discussed are origin to exposure, metabolism, matrices to analyse, analytical determination methods, determinants, and time trends. PMID:24369128

  16. The Multiple Endocrine Neoplasia Type 1 (MEN1) Tumor Suppressor Regulates Peroxisome Proliferator-Activated Receptor γ-Dependent Adipocyte Differentiation▿

    PubMed Central

    Dreijerink, Koen M. A.; Varier, Radhika A.; van Beekum, Olivier; Jeninga, Ellen H.; Höppener, Jo W. M.; Lips, Cornelis J. M.; Kummer, J. Alain; Kalkhoven, Eric; Timmers, H. T. Marc

    2009-01-01

    Menin, the product of the MEN1 (multiple endocrine neoplasia type 1) tumor suppressor gene, is involved in activation of gene transcription as part of an MLL1 (mixed-lineage leukemia 1)/MLL2 (KMT2A/B)-containing protein complex which harbors methyltransferase activity for lysine 4 of histone H3 (H3K4). As MEN1 patients frequently develop lipomas and peroxisome proliferator-activated receptor γ (PPARγ) is expressed in several MEN1-related tumor types, we investigated regulation of PPARγ activity by menin. We found that menin is required for adipocyte differentiation of murine 3T3-L1 cells and PPARγ-expressing mouse embryonic fibroblasts. Menin augments PPARγ target gene expression through recruitment of H3K4 methyltransferase activity. Menin interacts directly with the activation function 2 transcription activation domain of PPARγ in a ligand-independent fashion. Ligand-dependent coactivation, however, is dependent on the LXXLL motif of menin and the intact helix 12 of PPARγ. We propose that menin is an important factor in PPARγ-mediated adipogenesis and that loss of PPARγ function may contribute to lipoma development in MEN1 patients. PMID:19596783

  17. The multiple endocrine neoplasia type 1 (MEN1) tumor suppressor regulates peroxisome proliferator-activated receptor gamma-dependent adipocyte differentiation.

    PubMed

    Dreijerink, Koen M A; Varier, Radhika A; van Beekum, Olivier; Jeninga, Ellen H; Höppener, Jo W M; Lips, Cornelis J M; Kummer, J Alain; Kalkhoven, Eric; Timmers, H T Marc

    2009-09-01

    Menin, the product of the MEN1 (multiple endocrine neoplasia type 1) tumor suppressor gene, is involved in activation of gene transcription as part of an MLL1 (mixed-lineage leukemia 1)/MLL2 (KMT2A/B)-containing protein complex which harbors methyltransferase activity for lysine 4 of histone H3 (H3K4). As MEN1 patients frequently develop lipomas and peroxisome proliferator-activated receptor gamma (PPARgamma) is expressed in several MEN1-related tumor types, we investigated regulation of PPARgamma activity by menin. We found that menin is required for adipocyte differentiation of murine 3T3-L1 cells and PPARgamma-expressing mouse embryonic fibroblasts. Menin augments PPARgamma target gene expression through recruitment of H3K4 methyltransferase activity. Menin interacts directly with the activation function 2 transcription activation domain of PPARgamma in a ligand-independent fashion. Ligand-dependent coactivation, however, is dependent on the LXXLL motif of menin and the intact helix 12 of PPARgamma. We propose that menin is an important factor in PPARgamma-mediated adipogenesis and that loss of PPARgamma function may contribute to lipoma development in MEN1 patients.

  18. [Effect of thymostimulin on endocrine thymus function in thyroidectomized rats during suppressive hormone therapy].

    PubMed

    Hrinevych, Iu Ia; Bendiuh, H D; Ostapenko, O M

    2003-01-01

    Due to disorders of hormonal balance in the organism, a decrease in thymic endocrine function occurred in rats after thyroidectomy. After removing the thyroid gland, we observed 1,3-2,2-fold decrease in the level of thymic hormone thymulin in the blood serum. When thyroxin was applied at a suppressive dose, endocrine function of the thymus did not restore. Injections of thymostimulin (Tp1) or its combination with thyroxin to thyroidectomized animals restored the level of thymulin up to the level in the intact rats due to effects of either injected preparation or induction of substances possessing thymosine-like activity.

  19. A model for pharmacokinetics and physiological feedback among hormones of the testicular-pituitary axis in adult male rats: a framework for evaluating effects of endocrine active compounds.

    PubMed

    Barton, H A; Andersen, M E

    1998-10-01

    The testicular-hypothalamic-pituitary axis controls reproductive functions in males. A description of the basic physiological interactions in adult rats among testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) was developed, permitting simulation of hormone levels in testes and blood. This model was used to simulate hormone levels in intact, castrate, ethane dimethanesulfonate-treated, and antiandrogen-treated rats. A large gradient of testosterone concentrations from testicular interstitial fluid to low levels in peripheral blood is created by the testicular blood flow. The dominant feedback loop is positive regulation of testosterone synthesis by LH and negative feedback of testosterone on LH and FSH. The utility of the model for placing in vitro data in the context of in vivo physiology was illustrated for the case of continued synthesis of testosterone by the isolated testes. In the absence of blood flow, very low residual testosterone synthesis can substantially increase testosterone concentration in isolated testes. Effects of an exogenous endocrine active compound were illustrated by modeling altered LH and FSH regulation by testosterone in the presence of an antiandrogen acting as a competitive ligand for the androgen receptor. Increasing concentrations have no effect on steady-state hormone levels until sufficient levels of antiandrogen are achieved to reduce negative feedback of testosterone on LH and FSH. In summary, a model has been developed that provides a basis for initiating evaluations of key issues of concern for the risk assessment of endocrine active compounds including in vitro to in vivo extrapolation and their dose-response behaviors.

  20. Critical analysis of endocrine disruptive activity of triclosan and its relevance to human exposure through the use of personal care products.

    PubMed

    Witorsch, Raphael J

    2014-07-01

    This review examines the mammalian and human literature pertaining to the potential endocrine disruptive effects of triclosan (TCS). Dietary exposure to TCS consistently produces a dose-dependent decrease in serum thyroxine (T4) in rats without any consistent change in TSH or triiodothyronine (T3). Human studies reveal no evidence that the TCS exposure through personal care product use affects the thyroid system. TCS binds to both androgen and estrogen receptors in vitro with low affinity and evokes diverse responses (e.g., agonist, antagonist, or none) in steroid receptor transfected cell-based reporter assays. Two of three studies in rats have failed to show that TCS exposure suppresses male reproductive function in vivo. Three of four studies have failed to show that TCS possesses estrogenic (or uterotrophic) activity in rats. However, two studies reported that, while TCS lacks estrogenic activity, it can amplify the action of estrogen in vivo. The in vitro, in vivo, and epidemiologic studies reviewed herein show little evidence that TCS adversely affects gestation or postpartum development of offspring. Furthermore, previously reported toxicity testing in a variety of mammalian species shows little evidence that TCS adversely affects thyroid function, male and female reproductive function, gestation, or postpartum development of offspring. Finally, doses of TCS reported to produce hypothyroxinemia, and occasional effects on male and female reproduction, gestation, and offspring in animal studies are several orders of magnitude greater than the estimated exposure levels of TCS in humans. Overall, little evidence exists that TCS exposure through personal care product use presents a risk of endocrine disruptive adverse health effects in humans. PMID:24897554

  1. Critical analysis of endocrine disruptive activity of triclosan and its relevance to human exposure through the use of personal care products.

    PubMed

    Witorsch, Raphael J

    2014-07-01

    This review examines the mammalian and human literature pertaining to the potential endocrine disruptive effects of triclosan (TCS). Dietary exposure to TCS consistently produces a dose-dependent decrease in serum thyroxine (T4) in rats without any consistent change in TSH or triiodothyronine (T3). Human studies reveal no evidence that the TCS exposure through personal care product use affects the thyroid system. TCS binds to both androgen and estrogen receptors in vitro with low affinity and evokes diverse responses (e.g., agonist, antagonist, or none) in steroid receptor transfected cell-based reporter assays. Two of three studies in rats have failed to show that TCS exposure suppresses male reproductive function in vivo. Three of four studies have failed to show that TCS possesses estrogenic (or uterotrophic) activity in rats. However, two studies reported that, while TCS lacks estrogenic activity, it can amplify the action of estrogen in vivo. The in vitro, in vivo, and epidemiologic studies reviewed herein show little evidence that TCS adversely affects gestation or postpartum development of offspring. Furthermore, previously reported toxicity testing in a variety of mammalian species shows little evidence that TCS adversely affects thyroid function, male and female reproductive function, gestation, or postpartum development of offspring. Finally, doses of TCS reported to produce hypothyroxinemia, and occasional effects on male and female reproduction, gestation, and offspring in animal studies are several orders of magnitude greater than the estimated exposure levels of TCS in humans. Overall, little evidence exists that TCS exposure through personal care product use presents a risk of endocrine disruptive adverse health effects in humans.

  2. Validation and application of reporter gene assays for the determination of estrogenic and androgenic endocrine disruptor activity in sport supplements.

    PubMed

    Plotan, Monika; Elliott, Christopher T; Oplatowska, Michalina; Connolly, Lisa

    2012-07-01

    Previously developed estrogen and androgen mammalian reporter gene assays (RGAs) were assessed for their potential use as a quantitative screening method in the detection of estrogenic and androgenic endocrine disruptors (EDs) in sport supplements. The validation of both RGAs coupled with dispersive solid phase extraction (dSPE) was performed in accordance with European Commission Decision EC/2002/6579 for biological screening methods. Decision limits (CCα) and detection capabilities (CCβ) were established for both the estrogen and androgen RGAs. All samples were compliant with CCα and CCβ in both bioassays. Recovery rates were 96 % for 17β-estradiol and 115 % for dihydrotestosterone as obtained in their corresponding RGA. Both estrogens and androgens were stable in samples for more than 3 weeks, when stored at -20 °C. Specificity, good repeatability (coefficients of variation (CV), 12-25 %), reproducibility and robustness of both bioassays were also observed. Four different ED modes of action were determined for estrogens and androgens in 53 sport supplements, using the validated RGAs. This study revealed that 89 % of the investigated sport supplements contained estrogenic EDs and 51 % contained androgenic compounds. In conclusion, both bioassays are suitable for sport supplement screening of estrogenic and androgenic EDs.

  3. [Endocrine emergencies during pregnancy].

    PubMed

    Harbeck, B; Schütt, M; Sayk, F

    2012-03-01

    Endocrine emergencies during pregnancy can become life-threatening for both mother and fetus. In addition to some pregnancy-linked endocrine disorders, several pre-existing forms of endocrinopathy, such as Grave's disease, type 1 diabetes and adrenal insufficiency might deteriorate acutely during pregnancy. Early diagnosis and management are challenging because the classical symptoms are often modified by pregnancy. Laboratory tests are subject to altered physiological ranges and pharmacological options are limited while therapeutic goals are stricter than in the non-pregnant patient. This article focuses on endocrine emergencies complicating pregnancy. PMID:22349529

  4. Mitochondria and endocrine function of adipose tissue.

    PubMed

    Medina-Gómez, Gema

    2012-12-01

    Excess of adipose tissue is accompanied by an increase in the risk of developing insulin resistance, type 2 diabetes (T2D) and other complications. Nevertheless, total or partial absence of fat or its accumulation in other tissues (lipotoxicity) is also associated to these complications. White adipose tissue (WAT) was traditionally considered a metabolically active storage tissue for lipids while brown adipose tissue (BAT) was considered as a thermogenic adipose tissue with higher oxidative capacity. Nowadays, WAT is also considered an endocrine organ that contributes to energy homeostasis. Experimental evidence tends to link the malfunction of adipose mitochondria with the development of obesity and T2D. This review discusses the importance of mitochondrial function in adipocyte biology and the increased evidences of mitochondria dysfunction in these epidemics. New strategies targeting adipocyte mitochondria from WAT and BAT are also discussed as therapies against obesity and its complications in the near future. PMID:23168280

  5. Pyrethroid Pesticides as Endocrine Disruptors: Molecular Mechanisms in Vertebrates with a Focus on Fishes.

    PubMed

    Brander, Susanne M; Gabler, Molly K; Fowler, Nicholas L; Connon, Richard E; Schlenk, Daniel

    2016-09-01

    Pyrethroids are now the fourth most used group of insecticides worldwide. Employed in agriculture and in urban areas, they are detected in waterways at concentrations that are lethally and sublethally toxic to aquatic organisms. Highly lipophilic, pyrethroids accumulate in sediments and bioaccumulate in fishes. Additionally, these compounds are demonstrated to act as endocrine disrupting compounds (or EDCs) in mammals and fishes, and therefore interfere with endocrine signaling by blocking, mimicking, or synergizing endogenous hormones through direct receptor interactions, and indirectly via upstream signaling pathways. Pyrethroid metabolites have greater endocrine activity than their parent structures, and this activity is dependent on the enantiomer present, as some pyrethroids are chiral. Many EDCs studied thus far in fish have known estrogenic or antiestrogenic effects, and as such cause the inappropriate or altered expression of genes or proteins (i.e., Vtg-vitellogenin, Chg-choriogenin), often leading to physiological or reproductive effects. Additionally, these compounds can also interfere with other endocrine pathways and immune response. This review highlights studies that focus on the mechanisms of pyrethroid biotransformation and endocrine toxicity to fishes across a broad range of different pyrethroid types, and integrates literature on the in vitro and mammalian responses that inform these mechanisms. PMID:27464030

  6. Review of endocrine syndromes associated with tumours of non-endocrine origin

    PubMed Central

    Hobbs, C. B.; Miller, A. L.

    1966-01-01

    During the past 10 years there has been particular interest in the occurrence of a number of endocrine syndromes in association with tumours of organs other than the endocrines. Evidence is increasing to suggest that these result from the formation of hormone-like substances by the tumours. The clinical importance and theoretical implications of these syndromes constitute the justification for reviewing them here. PMID:5325646

  7. Syndromes that Link the Endocrine System and Genitourinary Tract.

    PubMed

    Özlük, Yasemin; Kılıçaslan, Işın

    2015-01-01

    The endocrine system and genitourinary tract unite in various syndromes. Genitourinary malignancies may cause paraneoplastic endocrine syndromes by secreting hormonal substances. These entities include Cushing`s syndrome, hypercalcemia, hyperglycemia, polycythemia, hypertension, and inappropriate ADH or HCG production. The most important syndromic scenarios that links these two systems are hereditary renal cancer syndromes with specific genotype/phenotype correlation. There are also some very rare entities in which endocrine and genitourinary systems are involved such as Carney complex, congenital adrenal hyperplasia and Beckwith-Wiedemann syndrome. We will review all the syndromes regarding manifestations present in endocrine and genitourinary organs.

  8. Endocrine-Disrupting Chemicals: An Endocrine Society Scientific Statement

    PubMed Central

    Diamanti-Kandarakis, Evanthia; Bourguignon, Jean-Pierre; Giudice, Linda C.; Hauser, Russ; Prins, Gail S.; Soto, Ana M.; Zoeller, R. Thomas; Gore, Andrea C.

    2009-01-01

    There is growing interest in the possible health threat posed by endocrine-disrupting chemicals (EDCs), which are substances in our environment, food, and consumer products that interfere with hormone biosynthesis, metabolism, or action resulting in a deviation from normal homeostatic control or reproduction. In this first Scientific Statement of The Endocrine Society, we present the evidence that endocrine disruptors have effects on male and female reproduction, breast development and cancer, prostate cancer, neuroendocrinology, thyroid, metabolism and obesity, and cardiovascular endocrinology. Results from animal models, human clinical observations, and epidemiological studies converge to implicate EDCs as a significant concern to public health. The mechanisms of EDCs involve divergent pathways including (but not limited to) estrogenic, antiandrogenic, thyroid, peroxisome proliferator-activated receptor γ, retinoid, and actions through other nuclear receptors; steroidogenic enzymes; neurotransmitter receptors and systems; and many other pathways that are highly conserved in wildlife and humans, and which can be modeled in laboratory in vitro and in vivo models. Furthermore, EDCs represent a broad class of molecules such as organochlorinated pesticides and industrial chemicals, plastics and plasticizers, fuels, and many other chemicals that are present in the environment or are in widespread use. We make a number of recommendations to increase understanding of effects of EDCs, including enhancing increased basic and clinical research, invoking the precautionary principle, and advocating involvement of individual and scientific society stakeholders in communicating and implementing changes in public policy and awareness. PMID:19502515

  9. Endocrine system: part 2.

    PubMed

    Hendry, Charles; Farley, Alistair; McLafferty, Ella; Johnstone, Carolyn

    2014-06-01

    This article, the last in the life sciences series, is the second of two articles on the endocrine system. It discusses human growth hormone, the pancreas and adrenal glands. The relationships between hormones and their unique functions are also explored. It is important that nurses understand how the endocrine system works and its role in maintaining health to provide effective care to patients. Several disorders caused by human growth hormone or that affect the pancreas and adrenal glands are examined.

  10. Short-Term Unilateral Resistance Training Results in Cross Education of Strength Without Changes in Muscle Size, Activation, or Endocrine Response.

    PubMed

    Beyer, Kyle S; Fukuda, David H; Boone, Carleigh H; Wells, Adam J; Townsend, Jeremy R; Jajtner, Adam R; Gonzalez, Adam M; Fragala, Maren S; Hoffman, Jay R; Stout, Jeffrey R

    2016-05-01

    Short-term unilateral resistance training results in cross education of strength without changes in muscle size, activation, or endocrine response. J Strength Cond Res 30(5): 1213-1223, 2016-The purpose of this study was to assess the cross education of strength and changes in the underlying mechanisms (muscle size, activation, and hormonal response) after a 4-week unilateral resistance training (URT) program. A group of 9 untrained men completed a 4-week URT program on the dominant leg (DOM), whereas cross education was measured in the nondominant leg (NON); and were compared with a control group (n = 8, CON). Unilateral isometric force (PKF), leg press (LP) and leg extension (LE) strength, muscle size (by ultrasonography) and activation (by electromyography) of the rectus femoris and vastus lateralis, and the hormonal response (testosterone, growth hormone, insulin, and insulin-like growth factor-1) were tested pretraining and posttraining. Group × time interactions were present for PKF, LP, LE, and muscle size in DOM and for LP in NON. In all interactions, the URT group improved significantly better than CON. There was a significant acute hormonal response to URT, but no chronic adaptation after the 4-week training program. Four weeks of URT resulted in an increase in strength and size of the trained musculature, and cross education of strength in the untrained musculature, which may occur without detectable changes in muscle size, activation, or the acute hormonal response.

  11. Fibroblast Growth Factor 23 and Klotho: Physiology and Pathophysiology of an Endocrine Network of Mineral Metabolism

    PubMed Central

    Hu, Ming Chang; Shiizaki, Kazuhiro; Kuro-o, Makoto; Moe, Orson W.

    2013-01-01

    The metabolically active and perpetually remodeling calcium phosphate–based endoskeleton in terrestrial vertebrates sets the demands on whole-organism calcium and phosphate homeostasis that involves multiple organs in terms of mineral flux and endocrine cross talk. The fibroblast growth factor (FGF)-Klotho endocrine networks epitomize the complexity of systems biology, and specifically, the FGF23-αKlotho axis highlights the concept of the skeleton holding the master switch of homeostasis rather than a passive target organ as hitherto conceived. Other than serving as a coreceptor for FGF23, αKlotho circulates as an endocrine substance with a multitude of effects. This review covers recent data on the physiological regulation and function of the complex FGF23-αKlotho network. Chronic kidney disease is a common pathophysiological state in which FGF23-αKlotho, a multiorgan endocrine network, is deranged in a self-amplifying vortex resulting in organ dysfunction of the utmost severity that contributes to its morbidity and mortality. PMID:23398153

  12. U.S. BURNING PLASMA ORGANIZATION ACTIVITIES

    SciTech Connect

    Raymond J. Fonck

    2009-08-11

    The national U.S. Burning Plasma Organization (USBPO) was formed to provide an umbrella structure in the U.S. fusion science research community. Its main purpose is the coordination of research activities in the U.S. program relevant to burning plasma science and preparations for participation in the international ITER experiment. This grant provided support for the continuing development and operations of the USBPO in its first years of existence. A central feature of the USBPO is the requirement for broad community participation in and governance of this effort. We concentrated on five central areas of activity of the USBPO during this grant period. These included: 1) activities of the Director and support staff in continuing management and development of the USBPO activity; 2) activation of the advisory Council; 3) formation and initial research activities of the research community Topical Groups; 4) formation of Task Groups to perform specific burning plasma related research and development activities; 5) integration of the USBPO community with the ITER Project Office as needed to support ITER development in the U.S.

  13. Adsorption of selected pharmaceuticals and an endocrine disrupting compound by granular activated carbon. 1. Adsorption capacity and kinetics

    SciTech Connect

    Yu, Z.; Peldszus, S.; Huck, P.M.

    2009-03-01

    The adsorption of two representative PhACs (naproxen and carbamazepine) and one EDC (nonylphenol) were evaluated on two granular activated carbons (GAC) namely coal-based Calgon Filtrasorb 400 and coconut shell-based PICA CTIF TE. The primary objective was to investigate preloading effects by natural organic matter (NOM) on adsorption capacity and kinetics under conditions and concentrations (i.e., ng/L) relevant for drinking water treatment. Isotherms demonstrated that all compounds were significantly negatively impacted by NOM fouling. Adsorption capacity reduction was most severe for the acidic naproxen, followed by the neutral carbamazepine and then the more hydrophobic nonylphenol. The GAC with the wider pore size distribution had considerably greater NOM loading, resulting in lower adsorption capacity. Different patterns for the change in Freundlich KF and 1/n with time revealed different competitive mechanisms for the different compounds. Mass transport coefficients determined by short fixed-bed (SFB) tests with virgin and preloaded GAC demonstrated that film diffusion primarily controls mass transfer on virgin and preloaded carbon. Naproxen suffered the greatest deteriorative effect on kinetic parameters due to preloading, followed by carbamazepine, and then nonylphenol. A type of surface NOM/biofilm, which appeared to add an additional mass transfer resistance layer and thus reduce film diffusion, was observed. In addition, electrostatic interactions between NOM/biofilm and the investigated compounds are proposed to contribute to the reduction of film diffusion. A companion paper building on this work describes treatability studies in pilot-scale GAC adsorbers and the effectiveness of a selected fixed-bed model. 32 refs., 3 figs., 2 tabs.

  14. Combined effects of dietary phytoestrogen and synthetic endocrine-active compound on reproductive development in Sprague-Dawley rats: genistein and methoxychlor.

    PubMed

    You, Li; Casanova, Mercedes; Bartolucci, Erika J; Fryczynski, Mary W; Dorman, David C; Everitt, Jeffrey I; Gaido, Kevin W; Ross, Susan M; Heck Hd, Henry d'A

    2002-03-01

    Humans and wildlife are frequently exposed to mixtures of endocrine active-compounds (EAC). The objective of the present study was to investigate the potential of the phytoestrogen genistein to influence the reproductive developmental toxicity of the endocrine-active pesticide methoxychlor. Three levels of genistein (0, 300, or 800 ppm) and two levels of methoxychlor (0 or 800 ppm) were used in this study. Sprague-Dawley rats were exposed to the two compounds, either alone or in combinations, through dietary administration to dams during pregnancy and lactation and to the offspring directly after weaning. Both compounds, methoxychlor in particular, were associated with reduced body growth at 800 ppm, but pregnancy outcome was not affected by either treatment. An acceleration of vaginal opening (VO) in the exposed female offspring was the only observed effect of genistein at 300 ppm. Exposure to 800 ppm genistein or 800 ppm methoxychlor caused accelerated VO and also altered estrous cyclicity toward persistent estrus in the female offspring. The estrogenic responses to genistein and methoxychlor administered together were apparently accumulative of the effects associated with each compound alone. Methoxychlor, but not genistein, delayed preputial separation (PPS) in the male rats. When administered with methoxychlor, genistein at 800 ppm enhanced the effect of methoxychlor on delaying PPS. Genistein and methoxychlor treatment did not change gender-specific motor activity patterns in either sex. To explore possible mechanisms for interaction between the two compounds on development, we performed estrogen receptor (ER)- and androgen receptor (AR)-based in vitro transcriptional activation assays using genistein and the primary methoxychlor metabolite 2,2-bis-(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE). While the in vitro assays supported the estrogenic effects of genistein and methoxychlor and the antiandrogenic effects of methoxychlor, the reactivity of these

  15. THE USE OF STRUCTURE-ACTIVITY RELATIONSHIPS IN INTEGRATING THE CHEMISTRY AND TOXICOLOGY OF ENDOCRINE DISRUPTING CHEMICALS

    EPA Science Inventory

    Structure activity relationships (SARs) are based on the principle that structurally similar chemicals should have similar biological activity. SARs relate specifically-defined toxicological activity of chemicals to their molecular structure and physico-chemical properties. To de...

  16. Endocrine Disrupting Contaminants—Beyond the Dogma

    PubMed Central

    Guillette, Louis J.

    2006-01-01

    Descriptions of endocrine disruption have largely been associated with wildlife and driven by observations documenting estrogenic, androgenic, antiandrogenic, and antithyroid actions. These actions, in response to exposure to ecologically relevant concentrations of various environmental contaminants, have now been established in numerous vertebrate species. However, many potential mechanisms and endocrine actions have not been studied. For example, the DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane] metabolite, p,p′-DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene] is known to disrupt prostaglandin synthesis in the uterus of birds, providing part of the explanation for DDT-induced egg shell thinning. Few studies have examined prostaglandin synthesis as a target for endocrine disruption, yet these hormones are active in reproduction, immune responses, and cardiovascular physiology. Future studies must broaden the basic science approach to endocrine disruption, thereby expanding the mechanisms and endocrine end points examined. This goal should be accomplished even if the primary influence and funding continue to emphasize a narrower approach based on regulatory needs. Without this broader approach, research into endocrine disruption will become dominated by a narrow dogma, focusing on a few end points and mechanisms. PMID:16818240

  17. Review of endocrine disorders associated with environmental toxicants and possible involved mechanisms.

    PubMed

    Maqbool, Faheem; Mostafalou, Sara; Bahadar, Haji; Abdollahi, Mohammad

    2016-01-15

    Endocrine disrupting chemicals (EDC) are released into environment from different sources. They are mainly used in packaging industries, pesticides and food constituents. Clinical evidence, experimental models, and epidemiological studies suggest that EDC have major risks for human by targeting different organs and systems in the body. Multiple mechanisms are involved in targeting the normal system, through estrogen receptors, nuclear receptors and steroidal receptors activation. In this review, different methods by which xenobiotics stimulate signaling pathways and genetic mutation or DNA methylation have been discussed. These methods help to understand the results of xenobiotic action on the endocrine system. Endocrine disturbances in the human body result in breast cancer, ovarian problems, thyroid eruptions, testicular carcinoma, Alzheimer disease, schizophrenia, nerve damage and obesity. EDC characterize a wide class of compounds such as organochlorinated pesticides, industrial wastes, plastics and plasticizers, fuels and numerous other elements that exist in the environment or are in high use during daily life. The interactions and mechanism of toxicity in relation to human general health problems, especially endocrine disturbances with particular reference to reproductive problems, diabetes, and breast, testicular and ovarian cancers should be deeply investigated. There should also be a focus on public awareness of these EDC risks and their use in routine life. Therefore, the aim of this review is to summarize all evidence regarding different physiological disruptions in the body and possible involved mechanisms, to prove the association between endocrine disruptions and human diseases. PMID:26497928

  18. Review of endocrine disorders associated with environmental toxicants and possible involved mechanisms.

    PubMed

    Maqbool, Faheem; Mostafalou, Sara; Bahadar, Haji; Abdollahi, Mohammad

    2016-01-15

    Endocrine disrupting chemicals (EDC) are released into environment from different sources. They are mainly used in packaging industries, pesticides and food constituents. Clinical evidence, experimental models, and epidemiological studies suggest that EDC have major risks for human by targeting different organs and systems in the body. Multiple mechanisms are involved in targeting the normal system, through estrogen receptors, nuclear receptors and steroidal receptors activation. In this review, different methods by which xenobiotics stimulate signaling pathways and genetic mutation or DNA methylation have been discussed. These methods help to understand the results of xenobiotic action on the endocrine system. Endocrine disturbances in the human body result in breast cancer, ovarian problems, thyroid eruptions, testicular carcinoma, Alzheimer disease, schizophrenia, nerve damage and obesity. EDC characterize a wide class of compounds such as organochlorinated pesticides, industrial wastes, plastics and plasticizers, fuels and numerous other elements that exist in the environment or are in high use during daily life. The interactions and mechanism of toxicity in relation to human general health problems, especially endocrine disturbances with particular reference to reproductive problems, diabetes, and breast, testicular and ovarian cancers should be deeply investigated. There should also be a focus on public awareness of these EDC risks and their use in routine life. Therefore, the aim of this review is to summarize all evidence regarding different physiological disruptions in the body and possible involved mechanisms, to prove the association between endocrine disruptions and human diseases.

  19. Long non-coding RNAs as regulators of the endocrine system

    PubMed Central

    Knoll, Marko; Lodish, Harvey F.; Sun, Lei

    2015-01-01

    Long non-coding RNAs (lncRNAs) are a large and diverse group of RNAs that are often lineage-specific and that regulate multiple biological functions. Many are nuclear and are essential parts of ribonucleoprotein complexes that modify chromatin segments and establish active or repressive chromatin states; others are cytosolic and regulate the stability of mRNA or act as microRNA sponges. This Review summarizes the current knowledge of lncRNAs as regulators of the endocrine system, with a focus on the identification and mode of action of several endocrine-important lncRNAs. We highlight lncRNAs that have a role in the development and function of pancreatic β cells, white and brown adipose tissue, and other endocrine organs, and discuss the involvement of these molecules in endocrine dysfunction (for example, diabetes mellitus). We also address the associations of lncRNAs with nuclear receptors involved in major hormonal signalling pathways, such as estrogen and androgen receptors, and the relevance of these associations in certain endocrine cancers. PMID:25560704

  20. Long non-coding RNAs as regulators of the endocrine system.

    PubMed

    Knoll, Marko; Lodish, Harvey F; Sun, Lei

    2015-03-01

    Long non-coding RNAs (lncRNAs) are a large and diverse group of RNAs that are often lineage-specific and that regulate multiple biological functions. Many are nuclear and are essential parts of ribonucleoprotein complexes that modify chromatin segments and establish active or repressive chromatin states; others are cytosolic and regulate the stability of mRNA or act as microRNA sponges. This Review summarizes the current knowledge of lncRNAs as regulators of the endocrine system, with a focus on the identification and mode of action of several endocrine-important lncRNAs. We highlight lncRNAs that have a role in the development and function of pancreatic β cells, white and brown adipose tissue, and other endocrine organs, and discuss the involvement of these molecules in endocrine dysfunction (for example, diabetes mellitus). We also address the associations of lncRNAs with nuclear receptors involved in major hormonal signalling pathways, such as estrogen and androgen receptors, and the relevance of these associations in certain endocrine cancers.

  1. Anthropogenic tracers, endocrine disrupting chemicals, and endocrine disruption in Minnesota lakes

    USGS Publications Warehouse

    Writer, J.H.; Barber, L.B.; Brown, G.K.; Taylor, H.E.; Kiesling, R.L.; Ferrey, M.L.; Jahns, N.D.; Bartell, S.E.; Schoenfuss, H.L.

    2010-01-01

    Concentrations of endocrine disrupting chemicals and endocrine disruption in fish were determined in 11 lakes across Minnesota that represent a range of trophic conditions and land uses (urban, agricultural, residential, and forested) and in which wastewater treatment plant discharges were absent. Water, sediment, and passive polar organic integrative samplers (POCIS) were analyzed for steroidal hormones, alkylphenols, bisphenol A, and other organic and inorganic molecular tracers to evaluate potential non-point source inputs into the lakes. Resident fish from the lakes were collected, and caged male fathead minnows were deployed to evaluate endocrine disruption, as indicated by the biological endpoints of plasma vitellogenin and gonadal histology. Endocrine disrupting chemicals, including bisphenol A, 17??-estradiol, estrone, and 4-nonylphenol were detected in 90% of the lakes at part per trillion concentrations. Endocrine disruption was observed in caged fathead minnows and resident fish in 90% of the lakes. The widespread but variable occurrence of anthropogenic chemicals in the lakes and endocrine disruption in fish indicates that potential sources are diverse, not limited to wastewater treatment plant discharges, and not entirely predictable based on trophic status and land use. ?? 2010.

  2. Hormones and endocrine disruptors in human seminal plasma.

    PubMed

    Hampl, R; Kubatova, J; Heracek, J; Sobotka, V; Starka, L

    2013-07-01

    Seminal plasma represents a unique environment for maturation, nutrition, and protection of male germ cells from damaging agents. It contains an array of organic as well as inorganic chemicals, encompassing a number of biologically and immunologically active compounds, including hormones. Seminal plasma contains also various pollutants transferred from outer environment known as endocrine disruptors. They interfere with hormones at the receptor level, act as inhibitors of their biosynthesis, and affect hormone regulation.In this minireview, the main groups of hormones detected in seminal plasma are summarized. Seminal gonadal steroids were investigated mostly with aim to use them as biomarkers of impaired spermatogenesis (sperm count, motility, morphology). Concentrations of hormones in the seminal plasma often differ considerably from the blood plasma levels in dependence on their origin. In some instances (dihydrotestosterone, estradiol), their informative value is higher than determination in blood.Out of peptide hormones detected in seminal plasma, peptides of transforming growth factor beta family, especially antimullerian hormone, and oligopeptides related to thyrotropin releasing hormone have the high informative value, while assessment of seminal gonadotropins and prolactin does not bring advantage over determination in blood.Though there is a large body of information about the endocrine disruptors' impact on male reproduction, especially with their potential role in decline of male reproductive functions within the last decades, there are only scarce reports on their presence in seminal plasma. Herein, the main groups of endocrine disruptors found in seminal plasma are reviewed, and the use of their determination for investigation of fertility disorders is discussed.

  3. Epicardial adipose tissue in endocrine and metabolic diseases.

    PubMed

    Iacobellis, Gianluca

    2014-05-01

    Epicardial adipose tissue has recently emerged as new risk factor and active player in metabolic and cardiovascular diseases. Albeit its physiological and pathological roles are not completely understood, a body of evidence indicates that epicardial adipose tissue is a fat depot with peculiar and unique features. Epicardial fat is able to synthesize, produce, and secrete bioactive molecules which are then transported into the adjacent myocardium through vasocrine and/or paracrine pathways. Based on these evidences, epicardial adipose tissue can be considered an endocrine organ. Epicardial fat is also thought to provide direct heating to the myocardium and protect the heart during unfavorable hemodynamic conditions, such as ischemia or hypoxia. Epicardial fat has been suggested to play an independent role in the development and progression of obesity- and diabetes-related cardiac abnormalities. Clinically, the thickness of epicardial fat can be easily and accurately measured. Epicardial fat thickness can serve as marker of visceral adiposity and visceral fat changes during weight loss interventions and treatments with drugs targeting the fat. The potential of modulating the epicardial fat with targeted pharmacological agents can open new avenues in the pharmacotherapy of endocrine and metabolic diseases. This review article will provide Endocrine's reader with a focus on epicardial adipose tissue in endocrinology. Novel, established, but also speculative findings on epicardial fat will be discussed from the unexplored perspective of both clinical and basic Endocrinologist.

  4. Glucuronidation and sulfonation, in vitro, of the major endocrine-active metabolites of methoxychlor in the channel catfish, Ictalurus punctatus, and induction following treatment with 3-methylcholanthrene

    PubMed Central

    James, Margaret O.; Stuchal, Leah D.; Nyagode, Beatrice A.

    2008-01-01

    of the conjugation pathways with those published for the demethylation of MXC showed that formation of the endocrine-active metabolites was more efficient than either conjugation pathway. Residues of OH-MXC and HPTE were detected in extracts of liver microsomes from MXC-treated fish. This work showed that although OH-MXC and HPTE could be eliminated by glucuronidation and sulfonation, the phase II pathways were less efficient than the phase I pathway leading to formation of these endocrine-active metabolites. PMID:18078677

  5. Metabolism of UV-filter benzophenone-3 by rat and human liver microsomes and its effect on endocrine-disrupting activity

    SciTech Connect

    Watanabe, Yoko; Kojima, Hiroyuki; Takeuchi, Shinji; Uramaru, Naoto; Sanoh, Seigo; Sugihara, Kazumi; Kitamura, Shigeyuki; Ohta, Shigeru

    2015-01-15

    Benzophenone-3 (2-hydroxy-4-methoxybenzophenone; BP-3) is widely used as sunscreen for protection of human skin and hair from damage by ultraviolet (UV) radiation. In this study, we examined the metabolism of BP-3 by rat and human liver microsomes, and the estrogenic and anti-androgenic activities of the metabolites. When BP-3 was incubated with rat liver microsomes in the presence of NADPH, 2,4,5-trihydroxybenzophenone (2,4,5-triOH BP) and 3-hydroxylated BP-3 (3-OH BP-3) were newly identified as metabolites, together with previously detected metabolites 5-hydroxylated BP-3 (5-OH BP-3), a 4-desmethylated metabolite (2,4-diOH BP) and 2,3,4-trihydroxybenzophenone (2,3,4-triOH BP). In studies with recombinant rat cytochrome P450, 3-OH BP-3 and 2,4,5-triOH BP were mainly formed by CYP1A1. BP-3 was also metabolized by human liver microsomes and CYP isoforms. In estrogen reporter (ER) assays using estrogen-responsive CHO cells, 2,4-diOH BP exhibited stronger estrogenic activity, 2,3,4-triOH BP exhibited similar activity, and 5-OH BP-3, 2,4,5-triOH BP and 3-OH BP-3 showed lower activity as compared to BP-3. Structural requirements for activity were investigated in a series of 14 BP-3 derivatives. When BP-3 was incubated with liver microsomes from untreated rats or phenobarbital-, 3-methylcholanthrene-, or acetone-treated rats in the presence of NADPH, estrogenic activity was increased. However, liver microsomes from dexamethasone-treated rats showed decreased estrogenic activity due to formation of inactive 5-OH BP-3 and reduced formation of active 2,4-diOH BP. Anti-androgenic activity of BP-3 was decreased after incubation with liver microsomes. - Highlights: • Metabolic modification of the endocrine-disrupting activity of BP-3 was examined. • 2,4,5-TriOH BP and 3-OH BP-3 were identified as new BP-3 metabolites. • 2,4-DiOH BP and 2,3,4-triOH BP exhibited high or similar estrogenic activities. • Estrogenic activity of BP-3 was enhanced by incubation with rat liver

  6. Redox activity of naphthalene secondary organic aerosol

    NASA Astrophysics Data System (ADS)

    McWhinney, R. D.; Zhou, S.; Abbatt, J. P. D.

    2013-04-01

    Chamber secondary organic aerosol (SOA) from low-NOx photooxidation of naphthalene by hydroxyl radical was examined with respect to its redox cycling behaviour using the dithiothreitol (DTT) assay. Naphthalene SOA was highly redox active, consuming DTT at an average rate of 118 ± 14 pmol per minute per μg of SOA material. Measured particle-phase masses of the major previously identified redox active products, 1,2- and 1,4-naphthoquinone, accounted for only 21 ± 3% of the observed redox cycling activity. The redox-active 5-hydroxy-1,4-naphthoquinone was identified as a new minor product of naphthalene oxidation, and including this species in redox activity predictions increased the predicted DTT reactivity to 30 ± 5% of observations. Similar attempts to predict redox behaviour of oxidised two-stroke engine exhaust particles by measuring 1,2-naphthoquinone, 1,4-naphthoquinone and 9,10-phenanthrenequinone predicted DTT decay rates only 4.9 ± 2.5% of those observed. Together, these results suggest that there are substantial unidentified redox-active SOA constituents beyond the small quinones that may be important toxic components of these particles. A gas-to-SOA particle partitioning coefficient was calculated to be (7.0 ± 2.5) × 10-4 m3 μg-1 for 1,4-naphthoquinone at 25 °C. This value suggests that under typical warm conditions, 1,4-naphthoquinone is unlikely to contribute strongly to redox behaviour of ambient particles, although further work is needed to determine the potential impact under conditions such as low temperatures where partitioning to the particle is more favourable. As well, higher order oxidation products that likely account for a substantial fraction of the redox cycling capability of the naphthalene SOA are likely to partition much more strongly to the particle phase.

  7. Endocrine neoplasms in familial syndromes of hyperparathyroidism.

    PubMed

    Li, Yulong; Simonds, William F

    2015-06-01

    Familial syndromes of hyperparathyroidism, including multiple endocrine neoplasia type 1 (MEN1), multiple endocrine neoplasia type 2A (MEN2A), and the hyperparathyroidism-jaw tumor (HPT-JT), comprise 2-5% of primary hyperparathyroidism cases. Familial syndromes of hyperparathyroidism are also associated with a range of endocrine and nonendocrine tumors, including potential malignancies. Complications of the associated neoplasms are the major causes of morbidities and mortalities in these familial syndromes, e.g., parathyroid carcinoma in HPT-JT syndrome; thymic, bronchial, and enteropancreatic neuroendocrine tumors in MEN1; and medullary thyroid cancer and pheochromocytoma in MEN2A. Because of the different underlying mechanisms of neoplasia, these familial tumors may have different characteristics compared with their sporadic counterparts. Large-scale clinical trials are frequently lacking due to the rarity of these diseases. With technological advances and the development of new medications, the natural history, diagnosis, and management of these syndromes are also evolving. In this article, we summarize the recent knowledge on endocrine neoplasms in three familial hyperparathyroidism syndromes, with an emphasis on disease characteristics, molecular pathogenesis, recent developments in biochemical and radiological evaluation, and expert opinions on surgical and medical therapies. Because these familial hyperparathyroidism syndromes are associated with a wide variety of tumors in different organs, this review is focused on those endocrine neoplasms with malignant potential. PMID:27207564

  8. Effects of Alcohol on the Endocrine System

    PubMed Central

    Rachdaoui, Nadia; Sarkar, Dipak K.

    2013-01-01

    Synopsis The endocrine system ensures a proper communication between various organs of the body to maintain a constant internal environment. The endocrine system also plays an essential role in enabling the body to respond and appropriately cope with changes in the internal or external environments, such as respond to stress and injury. These functions of the endocrine system to maintain body homeostasis are aided by its communication with the nervous system, immune system and body’s circadian mechanism. Chronic consumption of a large amount of alcohol disrupts the communication between nervous, endocrine and immune system and causes hormonal disturbances that lead to profound and serious consequences at physiological and behavioral levels. These alcohol-induced hormonal dysregulations affect the entire body and can result in various disorders such as stress abnormalities, reproductive deficits, body growth defect, thyroid problems, immune dysfunction, cancers, bone disease and psychological and behavioral disorders. This review summarizes the findings from human and animal studies that provide consistent evidence on the various effects of alcohol abuse on the endocrine system. PMID:24011889

  9. Oxidative stress and the ageing endocrine system.

    PubMed

    Vitale, Giovanni; Salvioli, Stefano; Franceschi, Claudio

    2013-04-01

    Ageing is a process characterized by a progressive decline in cellular function, organismal fitness and increased risk of age-related diseases and death. Several hundred theories have attempted to explain this phenomenon. One of the most popular is the 'oxidative stress theory', originally termed the 'free radical theory'. The endocrine system seems to have a role in the modulation of oxidative stress; however, much less is known about the role that oxidative stress might have in the ageing of the endocrine system and the induction of age-related endocrine diseases. This Review outlines the interactions between hormones and oxidative metabolism and the potential effects of oxidative stress on ageing of endocrine organs. Many different mechanisms that link oxidative stress and ageing are discussed, all of which converge on the induction or regulation of inflammation. All these mechanisms, including cell senescence, mitochondrial dysfunction and microRNA dysregulation, as well as inflammation itself, could be targets of future studies aimed at clarifying the effects of oxidative stress on ageing of endocrine glands.

  10. Endocrine Problems After Childhood Cancer: Precocious Puberty

    MedlinePlus

    ... cancer Precocious Puberty Version 3.0 - 10/08 Endocrine Problems after Childhood Cancer: Precocious Puberty Children treated ... the complex system of glands known as the endocrine system. What is the endocrine system? The endocrine ...

  11. What Is Women's Endocrine Health?

    MedlinePlus

    ... healthy lifestyle and harness the power to prevent endocrine disorders, the Power of Prevention. Childhood Childhood is a ... frequent at this time. Learning how to prevent endocrine disorders during this age is pivotal. Young Women At ...

  12. Your Endocrine System (For Kids)

    MedlinePlus

    ... Homework? Here's Help White House Lunch Recipes Your Endocrine System KidsHealth > For Kids > Your Endocrine System Print A A A Text Size en español ... a pea, is the "master gland" of the endocrine system. It makes and releases a bunch of hormones ...

  13. Photonic crystals with active organic materials

    NASA Astrophysics Data System (ADS)

    Wu, Yeheng

    The concept of photonic crystals, which involves periodically arranged dielectrics that form a new type of material having novel photonic properties, was first proposed about two decades ago. Since then, a number of applications in photonic technology have been explored. Specifically, organic and hybrid photonic crystals are promising because of the unique advantages of the organic materials. A one-dimensional (1D) photonic crystal (multilayer) has high reflectance across a certain wavelength range. We report on studies of 1D multilayer polymer films that were fabricated using spin-coating, free film stacking, and co-extrusion techniques. For example, a stack fabricated by placing a laser dye-doped gain medium between two multilayer reflecting polymer films forms a micro-resonator laser or distributed Bragg laser. The resulting laser system is made entirely of plastic and is only several tens of micrometers in thickness. When the gain, a dye-doped medium, comprises one type of a two-type multilayer film, it results a laser exhibiting distributed feedback. At the edge of the photonic band, the group velocity becomes small and the density of photon states becomes high, which leads to laser emission. Such distributed feedback lasers were fabricated using the co-extrusion technique. The refractive indices and the photonic lattice determine the photonic band gap, which can be tuned by changing these parameters. Materials with Kerr nonlinearity exhibit a change in refractive index depending on the incident intensity of the light. To demonstrate such switching, electrochemical etching techniques on silicon wafers were used to form two-dimensional (2D) photonic crystals. By incorporating the nonlinear organic material into the 2D structure, we have made all-optical switches. The reflection of a beam from the 2D photonic crystal can be controlled by another beam because it induces a refractive index change in the active material by altering the reflection band. A mid

  14. Ecotoxicological assessment of cimetidine and determination of its potential for endocrine disruption using three test organisms: Daphnia magna, Moina macrocopa, and Danio rerio.

    PubMed

    Lee, Saeram; Jung, Dawoon; Kho, Younglim; Ji, Kyunghee; Kim, Pilje; Ahn, Byeongwoo; Choi, Kyungho

    2015-09-01

    Cimetidine is a histamine H2-receptor antagonist used for treatment of gastrointestinal disorders. It is often detected in aquatic environments, but its ecotoxicological effects have not been well studied. Thus, ecotoxicity of cimetidine was evaluated using Daphnia magna and Moina macrocopa, and zebrafish (Danio rerio), and a predicted no effect concentration (PNEC) was derived. In D. magna, 48 h immobilization EC50 was determined at 394.9 mg L(-1). However, reproduction damages in D. magna were not found even at the maximum exposure level (30 mg L(-1)). For M. macrocopa, 48 h EC50 was found at 175.8 mg L(-1) and the 7 d reproduction no observed effect concentration (NOEC) was 1.1 mg L(-1). For D. rerio, 40 d growth NOEC was determined at 100 mg L(-1), the highest experimental concentration. The PNEC of cimetidine was estimated at 0.1 mg L(-1) based on M. macrocopa 7d reproduction NOEC. In 14 d adult zebrafish exposure, endocrine disruption potentials of cimetidine were observed. In male, decrease in plasma 17β-estradiol and testosterone levels, up-regulation of gonadal cyp17, and down-regulation of hepatic erα were observed at 300 mg L(-1). In female, increase in plasma E2 level and down-regulation of hepatic cyp1a were noted at 3 mg L(-1). Endocrine disruption effects were also observed in early life stage exposure. Up-regulation of erβ at 17d, and cyp19a and vtg at 40 d post fertilization were detected at 100 mg L(-1), and co-occurrence of ovary and putative testis was observed at as low as 1.1 mg L(-1). The results indicate that there is little evidence for cimetidine to cause direct ecological impact at the current ambient levels in the aquatic environment. However potential consequences of endocrine disruption following long-term exposure in aquatic environment deserves further investigation. PMID:25957140

  15. [Stress-induced changes in functional activity of the neuro-endocrine system: modulatory action of derinat].

    PubMed

    Fomicheva, E E; Filatenkova, T A; Shanin, S N; Rybakina, E G

    2009-03-01

    Changes in functional activity of HPA and HPG axes under stress influences of different intensity, and possible ways for their correction by native DNA preparation: derinat, possessing immune modulator effects, were studied. It was shown that the vector of changes in hormone's reactions of both axes did not depend on the intensity of stress influences: different models of stress increased corticosterone level and decreased testosterone level in rats' blood. Intraperitoneal injection of 10 and 50 mg/kg BW doses of Derinat to rats enhanced HPA and HPG axes activity, reversed stress-induced decrease of testosterone concentration in blood, that may indicate a stress-protective effect of derinat. Injection of derinat caused normalizing of stress-induced changes in immunomodulatory cytokines production within Lymphocyte Activating Factors, which regulate not only the immune system functions but also the functions of HPA and HPG axes.

  16. Endocrine investigation and therapy.

    PubMed

    McClure, R D

    1987-08-01

    The most commonly investigated testicular disorder is male infertility. Although endocrine causes are uncommon, they are potentially curable. A careful history and examination for subtle features of hypogonadism are important initiating steps. Understanding the appropriate use of both baseline and dynamic testing of the hypothalamic-pituitary-gonadal axis (and, in certain instances, the adrenal and thyroid glands) is extremely important.

  17. ENDOCRINE DISRUPTORS: LESSONS LEARNED

    EPA Science Inventory

    For more than ten years, major international efforts have been aimed at understanding the mechanism and extent of endocrine disruption in experimental models, wildlife, and people; its occurrence in the real world; and in developing tools for screening and prediction of risk. Mu...

  18. ISSUES IN ENDOCRINE DISRUPTION: COMPARING CRITICAL PERIODS OF HORMONE SENSITIVITY

    EPA Science Inventory

    Japanese medaka (Oryzias latipes) have been developed as a model species to compare the effects of endocrine active chemicals at critical life-stage periods of hormonal sensitivity, specifically as reproductively active adults, during the developmental period of differentiation, ...

  19. The evaluation and treatment of endocrine forms of hypertension.

    PubMed

    Velasco, Alejandro; Vongpatanasin, Wanpen

    2014-09-01

    Endocrine hypertension is an important secondary form of hypertension, identified in between 5% and 10% of general hypertensive population. Primary aldosteronism is the most common cause of endocrine hypertension, accounting for 1%-10% in uncomplicated hypertension and 7%-20% in resistant hypertension. Other less common causes of endocrine hypertension include Cushing syndrome, pheochromocytoma, thyroid disorders, and hyperparathyroidism. Diagnosis requires a high index of suspicion and the use of appropriate screening tests based on clinical presentation. Failure to make proper diagnosis may lead to catastrophic complications or irreversible hypertensive target organ damage. Accordingly, patients who are suspected to have endocrine hypertension should be referred to endocrinologists or hypertension specialists who are familiar with management of the specific endocrine disorders. PMID:25119722

  20. AroER Tri-Screen Is a Biologically Relevant Assay for Endocrine Disrupting Chemicals Modulating the Activity of Aromatase and/or the Estrogen Receptor

    PubMed Central

    Chen, Shiuan; Zhou, Dujin; Hsin, Li-Yu; Kanaya, Noriko; Wong, Cynthie; Yip, Richard; Sakamuru, Srilatha; Xia, Menghang; Yuan, Yate-Ching; Witt, Kristine; Teng, Christina

    2014-01-01

    Endocrine disrupting chemicals (EDCs) interfere with the biosynthesis, metabolism, and functions of steroid hormones, including estrogens and androgens. Aromatase enzyme converts androgen to estrogen. Thus, EDCs against aromatase significantly impact estrogen- and/or androgen-dependent functions, including the development of breast cancer. The current study aimed to develop a biologically relevant cell-based high-throughput screening assay to identify EDCs that act as aromatase inhibitors (AIs), estrogen receptor (ER) agonists, and/or ER antagonists. The AroER tri-screen assay was developed by stable transfection of ER-positive, aromatase-expressing MCF-7 breast cancer cells with an estrogen responsive element (ERE) driven luciferase reporter plasmid. The AroER tri-screen can identify: estrogenic EDCs, which increase luciferase signal without 17β-estradiol (E2); anti-estrogenic EDCs, which inhibit the E2-induced luciferase signal; and AI-like EDCs, which suppress a testosterone-induced luciferase signal. The assay was first optimized in a 96-well plate format and then miniaturized into a 1536-well plate format. The AroER tri-screen was demonstrated to be suitable for high-throughput screening in the 1536-well plate format, with a 6.9-fold signal-to-background ratio, a 5.4% coefficient of variation, and a screening window coefficient (Z-factor) of 0.78. The assay suggested that bisphenol A (BPA) functions mainly as an ER agonist. Results from screening the 446 drugs in the National Institutes of Health Clinical Collection revealed 106 compounds that modulated ER and/or aromatase activities. Among these, two AIs (bifonazole and oxiconazole) and one ER agonist (paroxetine) were confirmed through alternative aromatase and ER activity assays. These findings indicate that AroER tri-screen is a useful high-throughput screening system for identifying ER ligands and aromatase-inhibiting chemicals. PMID:24496634

  1. Pharmaceutically active compounds and endocrine disrupting chemicals in water, sediments and mollusks in mangrove ecosystems from Singapore.

    PubMed

    Bayen, Stéphane; Estrada, Elvagris Segovia; Juhel, Guillaume; Kit, Lee Wei; Kelly, Barry C

    2016-08-30

    This study investigated the occurrence of bisphenol A (BPA), atrazine and selected pharmaceutically active compounds (PhACs) in mangrove habitats in Singapore in 2012-2013, using multiple tools (sediment sampling, POCIS and filter feeder molluscs). Using POCIS, the same suite of contaminants (atrazine, BPA and eleven PhACs) was detected in mangrove waters in 28-days deployments in both 2012 and 2013. POCIS concentrations ranged from pg/L to μg/L. Caffeine, BPA, carbamazepine, E1, triclosan, sulfamerazine, sulfamethazine, and lincomycin were also detected in mangrove sediments from the low pg/g dw (e.g. carbamazepine) to ng/g dw (e.g. BPA). The detection of caffeine, carbamazepine, BPA, sulfamethoxazole or lincomycin in bivalve tissues also showed that these chemicals are bioavailable in the mangrove habitat. Since there are some indications that some pharmaceutically active substances may be biologically active in the low ppb range in marine species, further assessment should be completed based on ecotoxicological data specific to mangrove species. PMID:27393211

  2. Activity-dependent mobilization of the adhesion molecule polysialic NCAM to the cell surface of neurons and endocrine cells.

    PubMed Central

    Kiss, J Z; Wang, C; Olive, S; Rougon, G; Lang, J; Baetens, D; Harry, D; Pralong, W F

    1994-01-01

    The alpha-2,8-linked sialic acid polymer (PSA) on the neural cell adhesion molecule (NCAM) is an important regulator of cell surface interactions. We have examined the translocation of PSA-NCAM to the surface of cultured cortical neurons and insulin secreting beta cells under different conditions of cell activity. Endoneuraminidase N, an enzyme that specifically cleaves PSA chains, was used to remove pre-existing PSA from the plasma membrane and the re-expression of the molecule was monitored by immunocytochemistry. Punctate PSA immunostaining was restored on the surface of 68% of neurons within 1 h. This recovery was almost completely prevented by tetrodotoxin, suggesting that spontaneous electrical activity is required. K+ depolarization (50 mM) allowed recovery of PSA surface staining in the presence of tetrodotoxin and this effect required the presence of extracellular Ca2+. Rapid redistribution of PSA-NCAM to the surface of beta cells was observed under conditions that stimulate insulin secretion. Ca2+ channel inhibition decreased both PSA-NCAM expression and insulin secretion to control, non-stimulated levels. Finally, subcellular fractionation of an insulin-secreting cell line showed that the secretory vesicle fraction is highly enriched in PSA-NCAM. These results suggest that PSA-NCAM can be translocated to the cell surface via regulated exocytosis. Taken together, our results provide unprecedented evidence linking cell activity and PSA-NCAM expression, and suggest a mechanism for rapid modulation of cell surface interactions. Images PMID:7957094

  3. Pharmaceutically active compounds and endocrine disrupting chemicals in water, sediments and mollusks in mangrove ecosystems from Singapore.

    PubMed

    Bayen, Stéphane; Estrada, Elvagris Segovia; Juhel, Guillaume; Kit, Lee Wei; Kelly, Barry C

    2016-08-30

    This study investigated the occurrence of bisphenol A (BPA), atrazine and selected pharmaceutically active compounds (PhACs) in mangrove habitats in Singapore in 2012-2013, using multiple tools (sediment sampling, POCIS and filter feeder molluscs). Using POCIS, the same suite of contaminants (atrazine, BPA and eleven PhACs) was detected in mangrove waters in 28-days deployments in both 2012 and 2013. POCIS concentrations ranged from pg/L to μg/L. Caffeine, BPA, carbamazepine, E1, triclosan, sulfamerazine, sulfamethazine, and lincomycin were also detected in mangrove sediments from the low pg/g dw (e.g. carbamazepine) to ng/g dw (e.g. BPA). The detection of caffeine, carbamazepine, BPA, sulfamethoxazole or lincomycin in bivalve tissues also showed that these chemicals are bioavailable in the mangrove habitat. Since there are some indications that some pharmaceutically active substances may be biologically active in the low ppb range in marine species, further assessment should be completed based on ecotoxicological data specific to mangrove species.

  4. OECD test strategies and methods for endocrine disruptors.

    PubMed

    Gelbke, H P; Kayser, M; Poole, A

    2004-12-01

    The question whether (man-made or natural) chemical substances may have an adverse effect on the endocrine system has gained high visibility in the public as well as in the scientific community. This relates to possible effects on the environment as well as on human health for chemicals with (anti)estrogenic, (anti)androgenic or (anti)thyroid activity. Taking into account the broad universe of chemicals to which humans or the environment may be exposed, a sound testing strategy and robust test methods are urgently needed. Both subjects have been addressed by a specific OECD working group (EDTA-Endocrine Disruptor Testing and Assessment Task Force) involving regulatory agencies, the scientific community, chemical industry and NGOs. Like other organizations the OECD has adopted a tiered-testing strategy with the first tier using screening assays as quick and inexpensive tools, providing a way of generating alerts to potential endocrine activity that can be used to prioritize substances for definitive tests that then can determine the toxicological consequences of endocrine toxicity. The efforts of the OECD have therefore concentrated on the validation of specific screening and testing guidelines, like the uterotrophic, the Hershberger, and the "enhanced TG 407" test. The experimental testing necessary for this validation procedure is completed for the uterotrophic and the "enhanced TG 407" tests and near completion for the Hershberger assay. The data obtained so far have been published (for the uterotrophic assay) or will be submitted to the EDTA working group for final evaluation. Overall, the validation program has been very successful and should be sufficient for setting up OECD test guidelines for these experimental procedures. This will add substantially to the "tool-box" of OECD test methods that is available internationally to regulatory agencies and chemical industry for the identification and assessment of possible endocrine disruptors. Despite this success

  5. 75 FR 67963 - Endocrine Disruptor Screening Program (EDSP); Announcing the Availability of a Draft for Weight...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-04

    ... screening and testing chemicals with the potential to interact with the endocrine system. Tier 1 screening... AGENCY Endocrine Disruptor Screening Program (EDSP); Announcing the Availability of a Draft for Weight-of... submitted as part of EPA's two-tiered paradigm for screening and testing chemicals for endocrine activity...

  6. Biochemical, endocrine, and hematological factors in human oxygen tolerance extension: Predictive studies 6

    NASA Technical Reports Server (NTRS)

    Lambertsen, C. J.; Clark, J. M.

    1992-01-01

    The Predictive Studies VI (Biochemical, endocrine, and hematological factors in human oxygen tolerance extension) Program consisted of two related areas of research activity, integrated in design and performance, that were each based on an ongoing analysis of human organ oxygen tolerance data obtained for the continuous oxygen exposures of the prior Predictive Studies V Program. The two research areas effectively blended broad investigation of systematically varied intermittent exposure patterns in animals with very selective evaluation of specific exposure patterns in man.

  7. Neurogenin 3 Expressing Cells in the Human Exocrine Pancreas Have the Capacity for Endocrine Cell Fate

    PubMed Central

    Gomez, Danielle L.; O’Driscoll, Marci; Sheets, Timothy P.; Hruban, Ralph H.; Oberholzer, Jose; McGarrigle, James J.; Shamblott, Michael J.

    2015-01-01

    Neurogenin 3 (NGN3) is necessary and sufficient for endocrine differentiation during pancreatic development and is expressed by a population of progenitor cells that give rise exclusively to hormone-secreting cells within islets. NGN3 protein can be detected in the adult rodent pancreas only following certain types of injury, when it is transiently expressed by exocrine cells undergoing reprogramming to an endocrine cell fate. Here, NGN3 protein can be detected in 2% of acinar and duct cells in living biopsies of histologically normal adult human pancreata and 10% in cadaveric biopsies of organ donor pancreata. The percentage and total number of NGN3+ cells increase during culture without evidence of proliferation or selective cell death. Isolation of highly purified and viable NGN3+ cell populations can be achieved based on coexpression of the cell surface glycoprotein CD133. Transcriptome and targeted expression analyses of isolated CD133+ / NGN3+ cells indicate that they are distinct from surrounding exocrine tissue with respect to expression phenotype and Notch signaling activity, but retain high level mRNA expression of genes indicative of acinar and duct cell function. NGN3+ cells have an mRNA expression profile that resembles that of mouse early endocrine progenitor cells. During in vitro differentiation, NGN3+ cells express genes in a pattern characteristic of endocrine development and result in cells that resemble beta cells on the basis of coexpression of insulin C-peptide, chromogranin A and pancreatic and duodenal homeobox 1. NGN3 expression in the adult human exocrine pancreas marks a dedifferentiating cell population with the capacity to take on an endocrine cell fate. These cells represent a potential source for the treatment of diabetes either through ex vivo manipulation, or in vivo by targeting mechanisms controlling their population size and endocrine cell fate commitment. PMID:26288179

  8. Synthesis and evaluation of magnetic active charcoals for removal of environmental endocrine disrupter and heavy metal ion

    NASA Astrophysics Data System (ADS)

    Nakahira, A.; Nagata, H.; Takimura, M.; Fukunishi, K.

    2007-05-01

    In this study, alternative magnetic active charcoals (ACs) with magnetic responsibility for magnetic separations were synthesized by a chemical precipitation processing and subsequent heat treatments at 473K in H2 or air atmosphere. For various magnetic ACs, their adsorption abilities for bisphenol-A, methylene blue, and arsenic solution were evaluated. Magnetic AC with the same adsorption ability as normal AC could be collected and separated with a permanent magnet, demonstrating the successful synthesis of magnetic AC applicable to magnetic separations. Furthermore, magnetic AC heat treated in H2 possessed the high ability for arsenic removal.

  9. Environmental endocrine disruption: an effects assessment and analysis.

    PubMed Central

    Crisp, T M; Clegg, E D; Cooper, R L; Wood, W P; Anderson, D G; Baetcke, K P; Hoffmann, J L; Morrow, M S; Rodier, D J; Schaeffer, J E; Touart, L W; Zeeman, M G; Patel, Y M

    1998-01-01

    This report is an overview of the current state of the science relative to environmental endocrine disruption in humans, laboratory testing, and wildlife species. Background information is presented on the field of endocrinology, the nature of hormones, and potential sites for endocrine disruption, with specific examples of chemicals affecting these sites. An attempt is made to present objectively the issue of endocrine disruption, consider working hypotheses, offer opposing viewpoints, analyze the available information, and provide a reasonable assessment of the problem. Emphasis is placed on disruption of central nervous system--pituitary integration of hormonal and sexual behavioral activity, female and male reproductive system development and function, and thyroid function. In addition, the potential role of environmental endocrine disruption in the induction of breast, testicular, and prostate cancers, as well as endometriosis, is evaluated. The interrelationship of the endocrine and immune system is documented. With respect to endocrine-related ecological effects, specific case examples from the peer-reviewed literature of marine invertebrates and representatives of the five classes of vertebrates are presented and discussed. The report identifies some data gaps in our understanding of the environmental endocrine disruption issue and recommends a few research needs. Finally, the report states the U.S. Environmental Protection Agency Science Policy Council's interim position on endocrine disruption and lists some of the ongoing activities to deal with this matter. PMID:9539004

  10. Protein kinase A alterations in endocrine tumors.

    PubMed

    Yu, B; Ragazzon, B; Rizk-Rabin, M; Bertherat, J

    2012-09-01

    Various molecular and cellular alterations of the cyclic adenosine monophosphate (cAMP) pathway have been observed in endocrine tumors. Since protein kinase A (PKA) is a central key component of the cAMP pathway, studies of the alterations of PKA subunits in endocrine tumors reveal new aspects of the mechanisms of cAMP pathway alterations in human diseases. So far, most alterations have been observed for the regulatory subunits, mainly PRKAR1A and to a lower extent, PRKAR2B. One of the best examples of such alteration today is the multiple neoplasia syndrome Carney complex (CNC). The most common endocrine gland manifestations of CNC are pituitary GH-secreting adenomas, thyroid tumors, testicular tumors, and ACTH-independent Cushing's syndrome due to primary pigmented nodular adrenocortical disease (PPNAD). Heterozygous germline inactivating mutations of the PKA regulatory subunit RIα gene (PRKAR1A) are observed in about two-third of CNC patients, and also in patients with isolated PPNAD. PRKAR1A is considered as a tumor suppressor gene. Interestingly, these mutations can also be observed as somatic alterations in sporadic endocrine tumors. More than 120 different PRKAR1A mutations have been found today. Most of them lead to an unstable mutant mRNA, which will be degraded by nonsense mediated mRNA decay. In vitro and in vivo functional studies are in progress to understand the mechanisms of endocrine tumor development due to PKA regulatory subunits inactivation. PRKAR1A mutations stimulate in most models PKA activity, mimicking in some way cAMP pathway constitutive activation. Cross-talks with other signaling pathways summarized in this review have been described and might participate in endocrine tumorigenesis. PMID:22752956

  11. Biodegradation of endocrine-disrupting compounds by ligninolytic fungi: mechanisms involved in the degradation.

    PubMed

    Cajthaml, Tomáš

    2015-12-01

    Without any doubt, endocrine-disrupting compounds (EDCs) represent an environmental risk for wildlife and human beings. Endocrine-disrupting effects were found for many chemicals in products for personal use, industrial compounds and even in classical persistent organic pollutants (POPs). In order to understand the fate of EDCs in the environment, it is highly important to identify and to clarify the biodegradation mechanisms that can lead to their decomposition. Ligninolytic fungi (LF) are interesting microorganisms that are capable of participating in a variety of versatile decomposition mechanisms. The microorganisms represent a useful model group and, moreover, LF or their enzymes can be actively used for decontamination. Potential optimization of the decontamination process provides another important reason why it is necessary for understanding the mechanisms of EDC transformation. This minireview summarizes current knowledge about the LF biodegradation mechanisms of the most important micropollutants (xenoestrogens), including nonylphenols, bisphenol A and 17α-ethinylestradiol and polychlorinated biphenyls as POPs with endocrine-disrupting potency. Generally, LF exhibit the ability to either polymerize the target pollutants or to substantially decompose the original structure using ligninolytic enzymes and cytochrome P-450. Moreover, most of the transformation processes are accompanied by reduction of the endocrine-disrupting activity or ecotoxicity. PMID:24650234

  12. Biodegradation of endocrine-disrupting compounds by ligninolytic fungi: mechanisms involved in the degradation.

    PubMed

    Cajthaml, Tomáš

    2015-12-01

    Without any doubt, endocrine-disrupting compounds (EDCs) represent an environmental risk for wildlife and human beings. Endocrine-disrupting effects were found for many chemicals in products for personal use, industrial compounds and even in classical persistent organic pollutants (POPs). In order to understand the fate of EDCs in the environment, it is highly important to identify and to clarify the biodegradation mechanisms that can lead to their decomposition. Ligninolytic fungi (LF) are interesting microorganisms that are capable of participating in a variety of versatile decomposition mechanisms. The microorganisms represent a useful model group and, moreover, LF or their enzymes can be actively used for decontamination. Potential optimization of the decontamination process provides another important reason why it is necessary for understanding the mechanisms of EDC transformation. This minireview summarizes current knowledge about the LF biodegradation mechanisms of the most important micropollutants (xenoestrogens), including nonylphenols, bisphenol A and 17α-ethinylestradiol and polychlorinated biphenyls as POPs with endocrine-disrupting potency. Generally, LF exhibit the ability to either polymerize the target pollutants or to substantially decompose the original structure using ligninolytic enzymes and cytochrome P-450. Moreover, most of the transformation processes are accompanied by reduction of the endocrine-disrupting activity or ecotoxicity.

  13. Inhibition of focal adhesion kinase suppresses the adverse phenotype of endocrine-resistant breast cancer cells and improves endocrine response in endocrine-sensitive cells.

    PubMed

    Hiscox, Stephen; Barnfather, Peter; Hayes, Edd; Bramble, Pamela; Christensen, James; Nicholson, Robert I; Barrett-Lee, Peter

    2011-02-01

    Acquired resistance to endocrine therapy in breast cancer is a major clinical problem. Previous reports have demonstrated that cell models of acquired endocrine resistance have altered cell-matrix adhesion and a highly migratory phenotype, features which may impact on tumour spread in vivo. Focal adhesion kinase (FAK) is an intracellular kinase that regulates signalling pathways central to cell adhesion, migration and survival and its expression is frequently deregulated in breast cancer. In this study, we have used the novel FAK inhibitor PF573228 to address the role of FAK in the development of endocrine resistance. Whilst total-FAK expression was similar between endocrine-sensitive and endocrine-resistant MCF7 cells, FAK phosphorylation status (Y397 or Y861) was altered in resistance. PF573228 promoted a dose-dependent inhibition of FAK phosphorylation at Y397 but did not affect other FAK activation sites (pY407, pY576 and pY861). Endocrine-resistant cells were more sensitive to these inhibitory effects versus MCF7 (mean IC(50) for FAK pY397 inhibition: 0.43 μM, 0.05 μM and 0.13 μM for MCF7, TamR and FasR cells, respectively). Inhibition of FAK pY397 was associated with a reduction in TamR and FasR adhesion to, and migration over, matrix components. PF573228 as a single agent (0-1 μM) did not affect the growth of MCF7 cells or their endocrine-resistant counterparts. However, treatment of endocrine-sensitive cells with PF573228 and tamoxifen combined resulted in greater suppression of proliferation versus single agent treatment. Together these data suggest the importance of FAK in the process of endocrine resistance, particularly in the development of an aggressive, migratory cell phenotype and demonstrate the potential to improve endocrine response through combination treatment.

  14. Inhibition of focal adhesion kinase suppresses the adverse phenotype of endocrine-resistant breast cancer cells and improves endocrine response in endocrine-sensitive cells.

    PubMed

    Hiscox, Stephen; Barnfather, Peter; Hayes, Edd; Bramble, Pamela; Christensen, James; Nicholson, Robert I; Barrett-Lee, Peter

    2011-02-01

    Acquired resistance to endocrine therapy in breast cancer is a major clinical problem. Previous reports have demonstrated that cell models of acquired endocrine resistance have altered cell-matrix adhesion and a highly migratory phenotype, features which may impact on tumour spread in vivo. Focal adhesion kinase (FAK) is an intracellular kinase that regulates signalling pathways central to cell adhesion, migration and survival and its expression is frequently deregulated in breast cancer. In this study, we have used the novel FAK inhibitor PF573228 to address the role of FAK in the development of endocrine resistance. Whilst total-FAK expression was similar between endocrine-sensitive and endocrine-resistant MCF7 cells, FAK phosphorylation status (Y397 or Y861) was altered in resistance. PF573228 promoted a dose-dependent inhibition of FAK phosphorylation at Y397 but did not affect other FAK activation sites (pY407, pY576 and pY861). Endocrine-resistant cells were more sensitive to these inhibitory effects versus MCF7 (mean IC(50) for FAK pY397 inhibition: 0.43 μM, 0.05 μM and 0.13 μM for MCF7, TamR and FasR cells, respectively). Inhibition of FAK pY397 was associated with a reduction in TamR and FasR adhesion to, and migration over, matrix components. PF573228 as a single agent (0-1 μM) did not affect the growth of MCF7 cells or their endocrine-resistant counterparts. However, treatment of endocrine-sensitive cells with PF573228 and tamoxifen combined resulted in greater suppression of proliferation versus single agent treatment. Together these data suggest the importance of FAK in the process of endocrine resistance, particularly in the development of an aggressive, migratory cell phenotype and demonstrate the potential to improve endocrine response through combination treatment. PMID:20354780

  15. The role of activated carbon and disinfection on the removal of endocrine disrupting chemicals and non-steroidal anti-inflammatory drugs from wastewater.

    PubMed

    Noutsopoulos, Constantinos; Mamais, Daniel; Mpouras, Thanasis; Kokkinidou, Despina; Samaras, Vasilios; Antoniou, Korina; Gioldasi, Marianna

    2014-01-01

    Endocrine disrupting chemicals and non-steroidal anti-inflammatory drugs are two important groups of emerging pollutants due to their toxicological and chemical characteristics and their persistent detection in the aquatic environment. Wastewater treatment plants are a significant pathway for their transfer to the water courses. It is well evidenced that these chemicals are only partially removed through biological treatment of wastewater and therefore being detected in secondary effluents. This work focuses on the evaluation of the efficiency of two well-established disinfection technologies (chlorination and UV irradiation) along with UV/H2O2 and powdered activated carbon (PAC) to remove these chemicals from biologically treated wastewater. Based on the results it is shown that appreciable removal efficiencies due to chlorination should be expected for most of the target compounds, whereas this was not the case for ibuprofen and ketoprofen. With the exemption of diclofenac and ketoprofen direct UV irradiation did not efficiently removed target compounds for UV doses usually applied for disinfection purposes. The application of advanced UV treatment through the addition of H2O2 although resulted in increased removal of the target compounds is not sufficient at moderate UV and H2O2 doses to achieve satisfactory removal efficiencies. PAC use resulted in sufficient removal of target compounds although high PAC doses were required for some chemicals. Comparison of Freundlich isotherms of this study with those of other studies, derived employing water samples, suggested that the water matrix along with the target compounds concentration range can significantly affect the outcome of the experiments. PMID:24645450

  16. Computational Model of Steroidogenesis in Human H295R Cells to Predict Biochemical Response to Endocrine-Active Chemicals: Model Development for Metyrapone

    PubMed Central

    Terasaki, Natsuko; Yamazaki, Makoto; Conolly, Rory B.

    2009-01-01

    Background: An in vitro steroidogenesis assay using the human adrenocortical carcinoma cell line H295R is being evaluated as a possible screening assay to detect and assess the impact of endocrine-active chemicals (EACs) capable of altering steroid biosynthesis. Data interpretation and their quantitative use in human and ecological risk assessments can be enhanced with mechanistic computational models to help define mechanisms of action and improve understanding of intracellular concentrationresponse behavior. Objectives: The goal of this study was to develop a mechanistic computational model of the metabolic network of adrenal steroidogenesis to estimate the synthesis and secretion of adrenal steroids in human H295R cells and their biochemical response to steroidogenesis-disrupting EAC. Methods: We developed a deterministic model that describes the biosynthetic pathways for the conversion of cholesterol to adrenal steroids and the kinetics for enzyme inhibition by metryrapone (MET), a model EAC. Using a nonlinear parameter estimation method, the model was fitted to the measurements from an in vitro steroidogenesis assay using H295R cells. Results: Model-predicted steroid concentrations in cells and culture medium corresponded well to the time-course measurements from control and MET-exposed cells. A sensitivity analysis indicated the parameter uncertainties and identified transport and metabolic processes that most influenced the concentrations of primary adrenal steroids, aldosterone and cortisol. Conclusions: Our study demonstrates the feasibility of using a computational model of steroidogenesis to estimate steroid concentrations in vitro. This capability could be useful to help define mechanisms of action for poorly characterized chemicals and mixtures in support of predictive hazard and risk assessments with EACs. PMID:20123619

  17. The role of activated carbon and disinfection on the removal of endocrine disrupting chemicals and non-steroidal anti-inflammatory drugs from wastewater.

    PubMed

    Noutsopoulos, Constantinos; Mamais, Daniel; Mpouras, Thanasis; Kokkinidou, Despina; Samaras, Vasilios; Antoniou, Korina; Gioldasi, Marianna

    2014-01-01

    Endocrine disrupting chemicals and non-steroidal anti-inflammatory drugs are two important groups of emerging pollutants due to their toxicological and chemical characteristics and their persistent detection in the aquatic environment. Wastewater treatment plants are a significant pathway for their transfer to the water courses. It is well evidenced that these chemicals are only partially removed through biological treatment of wastewater and therefore being detected in secondary effluents. This work focuses on the evaluation of the efficiency of two well-established disinfection technologies (chlorination and UV irradiation) along with UV/H2O2 and powdered activated carbon (PAC) to remove these chemicals from biologically treated wastewater. Based on the results it is shown that appreciable removal efficiencies due to chlorination should be expected for most of the target compounds, whereas this was not the case for ibuprofen and ketoprofen. With the exemption of diclofenac and ketoprofen direct UV irradiation did not efficiently removed target compounds for UV doses usually applied for disinfection purposes. The application of advanced UV treatment through the addition of H2O2 although resulted in increased removal of the target compounds is not sufficient at moderate UV and H2O2 doses to achieve satisfactory removal efficiencies. PAC use resulted in sufficient removal of target compounds although high PAC doses were required for some chemicals. Comparison of Freundlich isotherms of this study with those of other studies, derived employing water samples, suggested that the water matrix along with the target compounds concentration range can significantly affect the outcome of the experiments.

  18. Mechanistic computational model of steroidogenesis in H295R cells: role of oxysterols and cell proliferation to improve predictability of biochemical response to endocrine active chemical--metyrapone.

    PubMed

    Breen, Miyuki; Breen, Michael S; Terasaki, Natsuko; Yamazaki, Makoto; Lloyd, Alun L; Conolly, Rory B

    2011-09-01

    The human adrenocortical carcinoma cell line H295R is being used as an in vitro steroidogenesis screening assay to assess the impact of endocrine active chemicals (EACs) capable of altering steroid biosynthesis. To enhance the interpretation and quantitative application of measurement data in risk assessments, we are developing a mechanistic computational model of adrenal steroidogenesis in H295R cells to predict the synthesis of steroids from cholesterol (CHOL) and their biochemical response to EACs. We previously developed a deterministic model that describes the biosynthetic pathways for the conversion of CHOL to steroids and the kinetics for enzyme inhibition by the EAC, metyrapone (MET). In this study, we extended our dynamic model by (1) including a cell proliferation model supported by additional experiments and (2) adding a pathway for the biosynthesis of oxysterols (OXY), which are endogenous products of CHOL not linked to steroidogenesis. The cell proliferation model predictions closely matched the time-course measurements of the number of viable H295R cells. The extended steroidogenesis model estimates closely correspond to the measured time-course concentrations of CHOL and 14 adrenal steroids both in the cells and in the medium and the calculated time-course concentrations of OXY from control and MET-exposed cells. Our study demonstrates the improvement of the extended, more biologically realistic model to predict CHOL and steroid concentrations in H295R cells and medium and their dynamic biochemical response to the EAC, MET. This mechanistic modeling capability could help define mechanisms of action for poorly characterized chemicals for predictive risk assessments.

  19. Postovulatory effect of repeated intravenous administration of ACTH on the contractile activity of the oviduct, ova transport and endocrine status of recently ovulated and unrestrained sows.

    PubMed

    Mwanza, A M; Madej, A; Kindahl, H; Lundeheim, N; Einarsson, S

    2000-11-01

    The effect of repeated intravenous administration of ACTH (Synacthen depot) on the contractile activity of the oviduct, ova transport and endocrine status was studied in 11 Swedish crossbred (Landrace x Yorkshire) multiparous sows. In the second estrus after weaning, the ACTH group (Group A, n=6) sows were administered 0.01 mg/kg body weight of ACTH every 6 h commencing 4 to 8 h after ovulation, whereas the control group (Group C, n=5) sows were administered saline solution. Immediately after standing estrus, a Millar pressure transducer was placed about 3 cm into the isthmus via a laparotomy. Blood samples for hormonal analyses and pressure recordings of the oviduct were collected from all sows until slaughter. After slaughter, the genital tract opposite to the side with the transducer was retrieved, and 3 equal isthmic segments and the first third of the uterine horn portion adjacent to the UTJ were flushed separately for ova recovery. Cortisol levels were significantly (P<0.05) elevated after ACTH administration. Progesterone and PGF2alpha metabolite levels were significantly (P<0.05) elevated only after the first ACTH administration. No significant differences (P>0.05) were seen in the mean pressure and frequencies of phasic pressure fluctuations either before or after every ACTH administration between Groups A and C. No significant difference (P>0.05) was seen in the proportion of ova recovered in the different segments between Groups A and C. It can be concluded from the present study that the administration of ACTH (0.01 mg/kg body weight) to sows at 4 to 8 h after ovulation, and after each subsequent ACTH administration, elevates cortisol levels, whereas progesterone and PGF2alpha metabolite levels are elevated only after the first treatment, and that this has no effect on the mean isthmic pressure, the frequency of phasic pressure fluctuations or ova transport. PMID:11192189

  20. The Herbicide Atrazine Activates Endocrine Gene Networks via Non-Steroidal NR5A Nuclear Receptors in Fish and Mammalian Cells

    PubMed Central

    Suzawa, Miyuki; Ingraham, Holly A.

    2008-01-01

    Atrazine (ATR) remains a widely used broadleaf herbicide in the United States despite the fact that this s-chlorotriazine has been linked to reproductive abnormalities in fish and amphibians. Here, using zebrafish we report that environmentally relevant ATR concentrations elevated zcyp19a1 expression encoding aromatase (2.2 µg/L), and increased the ratio of female to male fish (22 µg/L). ATR selectively increased zcyp19a1, a known gene target of the nuclear receptor SF-1 (NR5A1), whereas zcyp19a2, which is estrogen responsive, remained unchanged. Remarkably, in mammalian cells ATR functions in a cell-specific manner to upregulate SF-1 targets and other genes critical for steroid synthesis and reproduction, including Cyp19A1, StAR, Cyp11A1, hCG, FSTL3, LHß, INHα, αGSU, and 11ß-HSD2. Our data appear to eliminate the possibility that ATR directly affects SF-1 DNA- or ligand-binding. Instead, we suggest that the stimulatory effects of ATR on the NR5A receptor subfamily (SF-1, LRH-1, and zff1d) are likely mediated by receptor phosphorylation, amplification of cAMP and PI3K signaling, and possibly an increase in the cAMP-responsive cellular kinase SGK-1, which is known to be upregulated in infertile women. Taken together, we propose that this pervasive and persistent environmental chemical alters hormone networks via convergence of NR5A activity and cAMP signaling, to potentially disrupt normal endocrine development and function in lower and higher vertebrates. PMID:18461179

  1. Opioids and endocrine dysfunction

    PubMed Central

    Hester, Joan

    2012-01-01

    The endocrine effects of opioids used for the management of persistent pain are poorly understood by clinicians and patients, and hormone levels are rarely measured. It is recognized that opioids exert this effect via the hypothalamic-pituitary-gonadal axis. Additional effects on adrenal hormones, weight, blood pressure and bone density may also occur. Symptoms and signs of sex hormone deficiency occur in both men and women but are under-reported and are often clinically unrecognized. The potential effects of long term opioid therapy on the endocrine system should be explained to patients before opioid therapy is commenced. Monitoring of sex hormones is recommended; if there are deficiencies opioids should be tapered and withdrawn, if this is clinically acceptable. If opioid therapy has to continue, hormone replacement therapy should be initiated and monitored by an endocrinologist. PMID:26516462

  2. Endocrine disrupters as obesogens.

    PubMed

    Grün, Felix; Blumberg, Bruce

    2009-05-25

    The recent dramatic rise in obesity rates is an alarming global health trend that consumes an ever increasing portion of health care budgets in Western countries. The root cause of obesity is thought to be a prolonged positive energy balance. Hence, the major focus of preventative programs for obesity has been to target overeating and inadequate physical exercise. Recent research implicates environmental risk factors, including nutrient quality, stress, fetal environment and pharmaceutical or chemical exposure as relevant contributing influences. Evidence points to endocrine disrupting chemicals that interfere with the body's adipose tissue biology, endocrine hormone systems or central hypothalamic-pituitary-adrenal axis as suspects in derailing the homeostatic mechanisms important to weight control. This review highlights recent advances in our understanding of the molecular targets and mechanisms of action for these compounds and areas of future research needed to evaluate the significance of their contribution to obesity.

  3. Opioids and endocrine dysfunction.

    PubMed

    Seyfried, Oliver; Hester, Joan

    2012-02-01

    The endocrine effects of opioids used for the management of persistent pain are poorly understood by clinicians and patients, and hormone levels are rarely measured. It is recognized that opioids exert this effect via the hypothalamic-pituitary-gonadal axis. Additional effects on adrenal hormones, weight, blood pressure and bone density may also occur. Symptoms and signs of sex hormone deficiency occur in both men and women but are under-reported and are often clinically unrecognized. The potential effects of long term opioid therapy on the endocrine system should be explained to patients before opioid therapy is commenced. Monitoring of sex hormones is recommended; if there are deficiencies opioids should be tapered and withdrawn, if this is clinically acceptable. If opioid therapy has to continue, hormone replacement therapy should be initiated and monitored by an endocrinologist.

  4. Endocrine disorders in pregnancy.

    PubMed

    Sipes, S L; Malee, M P

    1992-12-01

    Disorders of the pituitary gland such as diabetes insipidus, pituitary adenomas, and hyperprolactinemia, disorders of the thyroid gland such as Graves' disease and hypothyroidism, and diseases of the adrenal gland such as adrenocortical insufficiency and Cushing's syndrome can complicate pregnancy. The goals of this article were to provide a basic scientific understanding of the normal function of these endocrine glands, their pregnancy-related changes, and suggestions for diagnosis and treatment of maternal and fetal endocrine disorders during pregnancy. Antenatal recognition and appropriate management of the disorders that especially affect the fetus (i.e., maternal Graves' disease, fetal hypothyroidism, and congenital adrenal hyperplasia) is essential in order to prevent fetal and neonatal morbidity and mortality.

  5. Sleep apnoea in endocrine diseases.

    PubMed

    Rosenow, F; McCarthy, V; Caruso, A C

    1998-03-01

    The pertinent literature on the prevalence, clinical manifestations and pathogenic mechanisms of sleep apnoea (SA) in endocrine diseases, namely acromegaly, Cushing syndrome, hypothyroidism and diabetes mellitus was reviewed. An increased prevalence is well documented in patients with active and treated acromegaly. While most authors report peripheral obstruction, due to hypertrophy of tongue and pharyngeal tissues, to be the cause of SA in acromegaly, some findings argue for a role of hormone-induced changes of central respiratory control. SA is also more common in hypothyroidism, especially when myxedema is present. The associated edema and myopathy appear to be of pathogenic importance. Thyroxin substitution is frequently effective for the treatment of SA but nCPAP can be necessary initially and in some patients even after remission of clinical signs of hypothyroidism. In Cushing disease and syndrome, parapharyngeal fat accumulation can cause SA, but no epidemiological information is available. In non insulin dependent diabetes (NIDDM), obesity is the common risk factor for both, nocturnal hypoxia and insulin resistance. In IDDM, the development of autonomic neuropathy may predispose to SA. Where treatment of the underlying endocrine disease is unable cure the associated SA, nCPAP is usually the treatment of first choice. More prospective studies are clearly needed to establish prevalences and resolve the controversies regarding pathogenesis. PMID:9613423

  6. Endocrine response to brain injury.

    PubMed

    Chioléro, R; Berger, M

    1994-11-01

    The neuroendocrine response (NER) is an essential component of the adaptive process to trauma, brain injury, and major surgery. While receiving additive humoral and neural afferent inputs, the brain nuclei responsible for the NER act mainly by efferent pathways to the hypothalamic-pituitary-adrenal (HPA) axis and the sympathoadrenal system, the activations of which induce subsequent circulatory and metabolic responses. The NER to brain injury is similar to the response observed in patients with extracerebral injury, even if the response after brain injury is extremely variable. Generally, there is a biphasic pattern, with a sympathoadrenal storm associated with variable and altered stimulation of the HPA during the ebb phase. The first phase is followed by a decrease in both responses while other endocrine changes develop, involving mainly the counter-regulatory, gonadal, and thyroid hormones. The outcome after brain injury is closely correlated with the intensity of these changes, particularly with catecholamine plasma levels and the severity of the low triiodothyronine syndrome. Alterations of the thyroid hormones are largely related to a reduction in peripheral deiodination of thyroxin. Recent research shows that increased free-radical production and decreased selenium (an antioxidant) serum levels play an important role in thyroid metabolism. Two major issues remain unsolved: a) the precise definition of cerebral death, since endocrine brain function is not abolished in the state currently defined as brain death; and b) the question of whether substitutive hormone therapy should be applied in severe brain injury.

  7. Management of fetal endocrine disorders.

    PubMed

    Hughes, I A

    2003-08-01

    A number of maternal endocrine disorders, when active during pregnancy, can have adverse effects on the newborn. Frequently, these affects can be anticipated as in Graves' disease, or the adverse effect can be prevented as in macrosomia in the infant of the diabetic mother. Occasionally, there are opportunities for prenatal treatment of a fetal endocrine disorder. For instance, a large goitre that may cause problems during delivery can be treated with thyroid hormones administered intra-amniotically or as analogues that cross the placenta. A uniquely effective form of treatment for prevention of a major birth defect is administration of dexamethasone to the mother to avoid virilisation of a female fetus with congenital adrenal hyperplasia (CAH). However, such treatment should only be conducted within the framework of a clinical trial as the long-term effects of exposure to potent glucocorticoids in utero are unknown. Intrauterine growth retardation, which affects about 5% of newborns, is currently not amenable to direct pharmacological treatment before birth. However, there are more practical options for managing this condition, including improved maternal nutrition and avoidance of toxins injurious to fetal growth.

  8. A Method for the Determination of Genetic Sex in the Fathead Minnow, Pimephales promelas, to Support Testing of Endocrine-active Chemicals

    EPA Science Inventory

    Fathead minnows are used as a model fish species for the characterization of the endocrine-disrupting potential of environmental contaminants. This research describes the development of a PCR method that can determine the genetic sex in this species. This method, when incorpora...

  9. [Endocrine problems during pregnancy].

    PubMed

    Mann, Klaus; Hintze, Gerhard

    2016-09-01

    Endocrine disorders may have an important influence on fertility, the course of a pregnancy and fetal development. For example, fertility is decreased and the risk of miscarriage is increased in women with autoimmune disorders, such as Addison's disease or autoimmune thyroiditis. Treatment of endocrine diseases in many cases has to be adapted during the course of a pregnancy. In patients with Addison's disease the dosage of hydrocortisone necessarily has to be increased. This is also valid for the time of delivery. Disorders of the thyroid gland are of great importance during pregnancy. If hypothyroidism is diagnosed in early pregnancy, immediate treatment with levothyroxine should be initiated. Iodine supplementation is strongly recommended in all pregnant and breast-feeding women. Treatment of Graves's disease will be performed during the first trimenon with propylthiouracile, afterwards with methimazole (thiamazole). In contrast, thyrotoxicosis due to hCG should not be treated with methimazole. In this paper, we present an overview on the most important endocrine disorders during pregnancy. PMID:27598917

  10. Endocrine taste cells.

    PubMed

    Kokrashvili, Zaza; Yee, Karen K; Ilegems, Erwin; Iwatsuki, Ken; Li, Yan; Mosinger, Bedrich; Margolskee, Robert F

    2014-06-01

    In taste cells, taste receptors, their coupled G proteins and downstream signalling elements mediate the detection and transduction of sweet, bitter and umami compounds. In some intestinal endocrine cells, taste receptors and gustducin contribute to the release of glucagon-like peptide 1 (GLP-1) and other gut hormones in response to glucose and non-energetic sweeteners. Conversely, taste cells have been found to express multiple hormones typically found in intestinal endocrine cells, e.g. GLP-1, glucagon, somatostatin and ghrelin. In the present study, by immunohistochemistry, multiple subsets of taste cells were found to express GLP-1. The release of GLP-1 from 'endocrine taste cells' into the bloodstream was examined. In wild-type mice, even after oesophagectomy and vagotomy, oral stimulation with glucose induced an elevation of GLP-1 levels in the bloodstream within 10 min. Stimulation of taste cell explants from wild-type mice with glucose led to the release of GLP-1 into the medium. Knocking out of the Tas1r3 gene did not eliminate glucose-stimulated GLP-1 release from taste cells in vivo. The present results indicate that a portion of the cephalic-phase rise in circulating GLP-1 levels is mediated by the direct release of GLP-1 from taste cells into the bloodstream.

  11. Evolution of endocrine adjuvant therapy for early breast cancer.

    PubMed

    Lønning, Per Eystein

    2010-04-01

    Endocrine treatment plays a pivotal role in the adjuvant therapy of patients harbouring oestrogen and/or progesterone receptor positive breast cancer. The objective of this paper is to critically review endocrine treatment options in early breast cancer focusing on ongoing development. Literature was collected through the ISI Web of Science and PubMed in January/February 2009 with subsequent update by December 2009, using the words breast cancer, endocrine therapy, oestrogen receptor and aromatase. Endocrine therapy improves outcome in early breast cancer. Yet several controversies remain. There has recently been a lack of general consensus regarding the limit of oestrogen receptor positivity. As for adjuvant therapy in general and use of aromatase inhibitors in particular, we need the results from ongoing studies to decide what may be the optimal duration of therapy and regimen (sequential treatment versus monotherapy; one drug compared with another). Further, there is a need to critically assess optimal use of endocrine therapy for metastatic disease among patients previously exposed to endocrine regimens in the adjuvant setting. While in general the mechanisms of resistance to endocrine therapy among ER positive tumours remains unknown, merging evidence suggest a role of different growth factor pathways, in particular HER-2 activation. Thus, particular attention is paid to the topic of HER-2 expression as a potential cause of endocrine resistance.

  12. Actions of endocrine-disrupting chemicals on stem/progenitor cells during development and disease.

    PubMed

    Kopras, Elizabeth; Potluri, Veena; Bermudez, Mei-Ling; Williams, Karin; Belcher, Scott; Kasper, Susan

    2014-04-01

    Development and fate of the stem cell are regulated by extrinsic signals from the environment. Endocrine-disrupting chemicals which perturb hormonal signaling in utero and during early childhood may cause deregulation of multiple developmental processes, ranging from breakdown of stem cell niche architecture, developmental reprograming and altered stem cell fate to impaired organ and gonad development and sexual differentiation. Therefore, study of the environmental effects on stem cell integrity and normal development is a new and emerging focus for developmental biologists and cell toxicologists. When combined with new human and mouse stem cell-based models, stem cell differentiation dynamics can be studied in more biologically relevant ways. In this study, we review the current status of our understanding of the molecular mechanisms by which endocrine disruptors alter embryonic stem cell and adult stem/progenitor cell fate, organ development, cancer stem cell activity, and tumorigenesis.

  13. Endocrine Aspects of Environmental "Obesogen" Pollutants.

    PubMed

    Nappi, Francesca; Barrea, Luigi; Di Somma, Carolina; Savanelli, Maria Cristina; Muscogiuri, Giovanna; Orio, Francesco; Savastano, Silvia

    2016-01-01

    Growing evidence suggests the causal link between the endocrine-disrupting chemicals (EDCs) and the global obesity epidemics, in the context in the so-called "obesogenic environment". Dietary intake of contaminated foods and water, especially in association with unhealthy eating pattern, and inhalation of airborne pollutants represent the major sources of human exposure to EDCs. This is of particular concern in view of the potential impact of obesity on chronic non-transmissible diseases, such as type 2 diabetes, cardiovascular disease, and hormone-sensitive cancers. The key concept is the identification of adipose tissue not only as a preferential site of storage of EDCs, but also as an endocrine organ and, as such, susceptible to endocrine disruption. The timing of exposure to EDCs is critical to the outcome of that exposure, with early lifetime exposures (e.g., fetal or early postnatal) particularly detrimental because of their permanent effects on obesity later in life. Despite that the mechanisms operating in EDCs effects might vary enormously, this minireview is aimed to provide a general overview on the possible association between the pandemics of obesity and EDCs, briefly describing the endocrine mechanisms linking EDCs exposure and latent onset of obesity. PMID:27483295

  14. Executive Summary to EDC-2: The Endocrine Society's Second Scientific Statement on Endocrine-Disrupting Chemicals.

    PubMed

    Gore, A C; Chappell, V A; Fenton, S E; Flaws, J A; Nadal, A; Prins, G S; Toppari, J; Zoeller, R T

    2015-12-01

    This Executive Summary to the Endocrine Society's second Scientific Statement on environmental endocrine-disrupting chemicals (EDCs) provides a synthesis of the key points of the complete statement. The full Scientific Statement represents a comprehensive review of the literature on seven topics for which there is strong mechanistic, experimental, animal, and epidemiological evidence for endocrine disruption, namely: obesity and diabetes, female reproduction, male reproduction, hormone-sensitive cancers in females, prostate cancer, thyroid, and neurodevelopment and neuroendocrine systems. EDCs such as bisphenol A, phthalates, pesticides, persistent organic pollutants such as polychlorinated biphenyls, polybrominated diethyl ethers, and dioxins were emphasized because these chemicals had the greatest depth and breadth of available information. The Statement also included thorough coverage of studies of developmental exposures to EDCs, especially in the fetus and infant, because these are critical life stages during which perturbations of hormones can increase the probability of a disease or dysfunction later in life. A conclusion of the Statement is that publications over the past 5 years have led to a much fuller understanding of the endocrine principles by which EDCs act, including nonmonotonic dose-responses, low-dose effects, and developmental vulnerability. These findings will prove useful to researchers, physicians, and other healthcare providers in translating the science of endocrine disruption to improved public health. PMID:26414233

  15. Executive Summary to EDC-2: The Endocrine Society's Second Scientific Statement on Endocrine-Disrupting Chemicals.

    PubMed

    Gore, A C; Chappell, V A; Fenton, S E; Flaws, J A; Nadal, A; Prins, G S; Toppari, J; Zoeller, R T

    2015-12-01

    This Executive Summary to the Endocrine Society's second Scientific Statement on environmental endocrine-disrupting chemicals (EDCs) provides a synthesis of the key points of the complete statement. The full Scientific Statement represents a comprehensive review of the literature on seven topics for which there is strong mechanistic, experimental, animal, and epidemiological evidence for endocrine disruption, namely: obesity and diabetes, female reproduction, male reproduction, hormone-sensitive cancers in females, prostate cancer, thyroid, and neurodevelopment and neuroendocrine systems. EDCs such as bisphenol A, phthalates, pesticides, persistent organic pollutants such as polychlorinated biphenyls, polybrominated diethyl ethers, and dioxins were emphasized because these chemicals had the greatest depth and breadth of available information. The Statement also included thorough coverage of studies of developmental exposures to EDCs, especially in the fetus and infant, because these are critical life stages during which perturbations of hormones can increase the probability of a disease or dysfunction later in life. A conclusion of the Statement is that publications over the past 5 years have led to a much fuller understanding of the endocrine principles by which EDCs act, including nonmonotonic dose-responses, low-dose effects, and developmental vulnerability. These findings will prove useful to researchers, physicians, and other healthcare providers in translating the science of endocrine disruption to improved public health.

  16. Potentiating effect of an endocrine disruptor, paranonylphenol, on the generation of reactive oxygen species (ROS) in human venous blood -- association with the activation of signal transduction pathway.

    PubMed

    Okai, Yasuji; Sato, Eisuke F; Higashi-Okai, Kiyoka; Inoue, Masayasu

    2007-09-01

    An endocrine disruptor, para-nonylphenol (NP), caused a dose-dependent stimulatory effect on the generation of reactive oxygen species (ROS) in human whole blood from 50 to 1000 microM, which was measured by chemiluminescence generation. ROS-scavenging enzymes such as catalase and superoxide dismutase, and the lipophilic antioxidative agents, alpha-tocopherol and beta-carotene, showed preventive effects on NP-induced ROS generation. To analyze the biochemical mechanism of NP-induced ROS generation in human blood, we investigated the effects of different types of metabolic inhibitors on the activation pathways of ROS generation. An NADPH-dependent oxidase inhibitor, diphenyl iodonium chloride (DPI), and a myeloperoxidase inhibitor, sodium azide (NaN3), showed remarkable inhibitory effects on ROS generation induced by NP, but an inhibitor against mitochondrial respiratory function, potassium cyanide (KCN), did not exhibit a significant effect. Furthermore, a phosphatidylinositol-3 (PI3) kinase inhibitor, wortmannin, and a tyrosine kinase inhibitor, protein phosphorylation inhibitor 1 (PP1), caused a strong suppression of NP-induced ROS generation. Selective protein kinase C inhibitor, Ro-32-0432, p38 MAP kinase inhibitor, SB-203580, and ERK MAP kinase inhibitor, PD 98059, showed significant suppressive effects on NP-induced ROS generation. In addition, when human blood was exposed to lower concentrations (5-50 microM) of NP, they did not cause the significant ROS generation by themselves, but the priming and synergistic effects of NP were detected by the addition of secondary stimulants, opsonized zymosan (OZ) or phorbol myristate acetate (PMA). The analysis of the priming and synergistic effects of NP on OZ- or PMA-dependent ROS generation by antioxidative substances and metabolic inhibitors showed similar results compared with those of human blood treated with NP alone. These results suggest that NP causes an enhancing effect by itself, or priming and synergistic

  17. The gastrin-releasing peptide analog bombesin preserves exocrine and endocrine pancreas morphology and function during parenteral nutrition

    PubMed Central

    Pierre, Joseph F.; Neuman, Joshua C.; Brill, Allison L.; Brar, Harpreet K.; Thompson, Mary F.; Cadena, Mark T.; Connors, Kelsey M.; Busch, Rebecca A.; Heneghan, Aaron F.; Cham, Candace M.; Jones, Elaina K.; Kibbe, Carly R.; Davis, Dawn B.; Groblewski, Guy E.; Kudsk, Kenneth A.

    2015-01-01

    Stimulation of digestive organs by enteric peptides is lost during total parental nutrition (PN). Here we examine the role of the enteric peptide bombesin (BBS) in stimulation of the exocrine and endocrine pancreas during PN. BBS protects against exocrine pancreas atrophy and dysfunction caused by PN. BBS also augments circulating insulin levels, suggesting an endocrine pancreas phenotype. While no significant changes in gross endocrine pancreas morphology were observed, pancreatic islets isolated from BBS-treated PN mice showed a significantly enhanced insulin secretion response to the glucagon-like peptide-1 (GLP-1) agonist exendin-4, correlating with enhanced GLP-1 receptor expression. BBS itself had no effect on islet function, as reflected in low expression of BBS receptors in islet samples. Intestinal BBS receptor expression was enhanced in PN with BBS, and circulating active GLP-1 levels were significantly enhanced in BBS-treated PN mice. We hypothesized that BBS preserved islet function indirectly, through the enteroendocrine cell-pancreas axis. We confirmed the ability of BBS to directly stimulate intestinal enteroid cells to express the GLP-1 precursor preproglucagon. In conclusion, BBS preserves the exocrine and endocrine pancreas functions during PN; however, the endocrine stimulation is likely indirect, through the enteroendocrine cell-pancreas axis. PMID:26185331

  18. ENDOCRINE DISRUPTING CONTAMINANTS AND ALLIGATOR EMBRYOS: A LESSON FROM WILDLIFE?

    EPA Science Inventory

    Many xenobiotic compounds introduced into the environment by human activity adversely affect wildlife. A number of these contaminants have been hypothesized to induce non lethal, multigenerational effects by acting as endocrine disrupting agents. One case is that of the alligator...

  19. Genomic organization and transcriptional modulation in response to endocrine disrupting chemicals of three vitellogenin genes in the self-fertilizing fish Kryptolebias marmoratus.

    PubMed

    Kim, Bo-Mi; Lee, Min Chul; Kang, Hye-Min; Rhee, Jae-Sung; Lee, Jae-Seong

    2016-04-01

    Vitellogenin (Vtg) is the precursor of egg yolk proteins, and its expression has been used as a reliable biomarker for estrogenic contamination in the aquatic environment. To examine the biomarker potential of the self-fertilizing killifish Kryptolebias marmoratus Vtgs (Km-Vtgs), full genomic DNAs of Km-Vtgs-Aa, Km-Vtgs-Ab, and Km-Vtgs-C were cloned, sequenced, and characterized. Three Vtg genes in K. marmoratus are tandemly placed in a 550 kb section of the same chromosome. In silico analysis of promoter regions revealed that both the Km-Vtgs-Aa and Km-Vtgs-Ab genes had an estrogen response element (ERE), but the Km-Vtgs-C gene did not. However, all three Km-Vtgs genes had several ERE-half sites in their promoter regions. Phylogenetic analysis demonstrated that the three deduced amino acid residues were highly conserved with conventional Vtgs protein, forming distinctive clades within teleost Vtgs. Liver tissue showed the highest expression of Km-Vtg transcripts in all tested tissues (brain/pituitary, eye, gonad, intestine, skin, and muscle) in response to endocrine disrupting chemical (EDC)-exposed conditions. Km-Vtg transcripts were significantly increased in response to 17β-estradiol (E2), tamoxifen (TMX), 4-n-nonylphenol (NP), bisphenol A (BPA), and octylphenol (OP) over 24hr exposure. The Km-Vtg-A gene was highly expressed compared to the control in response to NP and OP. EDC-induced modulatory patterns of Km-Vtg gene expression were different depending on tissue, gender, and isoforms. PMID:27090710

  20. Hypothesis: Musculin is a hormone secreted by skeletal muscle, the body's largest endocrine organ. Evidence for actions on the endocrine pancreas to restrain the beta-cell mass and to inhibit insulin secretion and on the hypothalamus to co-ordinate the neuroendocrine and appetite responses to exercise.

    PubMed

    Engler, Dennis

    2007-01-01

    Recent studies indicate that skeletal muscle may act as an endocrine organ by secreting interleukin-6 (IL-6) into the systemic circulation. From an analysis of the actions of IL-6 and of additional literature, we postulate that skeletal muscle also secretes an unidentified hormone, which we have named Musculin (Latin: musculus = muscle), which acts on the pancreatic beta-cell to restrain the size of the (beta-cell mass and to tonically inhibit insulin secretion and biosynthesis. It is suggested that the amount of Musculin secreted is determined by, and is positively correlated with, the prevailing insulin sensitivity of skeletal muscle, thereby accounting for the hyperinsulinemia that occurs in insulin resistant disorders such as type 2 diabetes mellitus, obesity, and the polycystic ovary syndrome. In addition, it is postulated that Musculin acts on the hypothalamus (arcuate nucleus, dorsomedial hypothalamic nucleus) to co-ordinate the neuroendocrine and appetite responses to exercise. However, the possibilities that Musculin may act on additional central nervous system sites and that an additional hormone(s) may be responsible for these actions are not excluded. It is suggested that a search be made for Musculin, since analogues of such a substance may be of therapeutic benefit in the treatment of the current global diabetes and obesity epidemic.

  1. Endocrine active chemicals, pharmaceuticals, and other chemicals of concern in surface water, wastewater-treatment plant effluent, and bed sediment, and biological characteristics in selected streams, Minnesota-design, methods, and data, 2009

    USGS Publications Warehouse

    Lee, Kathy E.; Langer, Susan K.; Barber, Larry B.; Writer, Jeff H.; Ferrey, Mark L.; Schoenfuss, Heiko L.; Furlong, Edward T.; Foreman, William T.; Gray, James L.; ReVello, Rhiannon C.; Martinovic, Dalma; Woodruff, Olivia R.; Keefe, Steffanie H.; Brown, Greg K.; Taylor, Howard E.; Ferrer, Imma; Thurman, E. Michael

    2011-01-01

    This report presents the study design, environmental data, and quality-assurance data for an integrated chemical and biological study of selected streams or lakes that receive wastewater-treatment plant effluent in Minnesota. This study was a cooperative effort of the U.S. Geological Survey, the Minnesota Pollution Control Agency, St. Cloud State University, the University of St. Thomas, and the University of Colorado. The objective of the study was to identify distribution patterns of endocrine active chemicals, pharmaceuticals, and other organic and inorganic chemicals of concern indicative of wastewater effluent, and to identify biological characteristics of estrogenicity and fish responses in the same streams. The U.S. Geological Survey collected and analyzed water, bed-sediment, and quality-assurance samples, and measured or recorded streamflow once at each sampling location from September through November 2009. Sampling locations included surface water and wastewater-treatment plant effluent. Twenty-five wastewater-treatment plants were selected to include continuous flow and periodic release facilities with differing processing steps (activated sludge or trickling filters) and plant design flows ranging from 0.002 to 10.9 cubic meters per second (0.04 to 251 million gallons per day) throughout Minnesota in varying land-use settings. Water samples were collected from the treated effluent of the 25 wastewater-treatment plants and at one point upstream from and one point downstream from wastewater-treatment plant effluent discharges. Bed-sediment samples also were collected at each of the stream or lake locations. Water samples were analyzed for major ions, nutrients, trace elements, pharmaceuticals, phytoestrogens and pharmaceuticals, alkylphenols and other neutral organic chemicals, carboxylic acids, and steroidal hormones. A subset (25 samples) of the bed-sediment samples were analyzed for carbon, wastewater-indicator chemicals, and steroidal hormones; the

  2. Effect of water composition on TiO2 photocatalytic removal of endocrine disrupting compounds (EDCs) and estrogenic activity from secondary effluent.

    PubMed

    Zhang, Wenlong; Li, Yi; Su, Yaling; Mao, Kai; Wang, Qing

    2012-05-15

    The effect of inorganic ions and dissolved organic matter (DOM) on the TiO(2) photocatalytic removal of estrogenic activity from secondary effluents of municipal wastewater treatment plants was investigated. The presence of HPO(4)(2-), NH(4)(+), and HCO(3)(-) resulted in a significantly negative impact on the photocatalytic removal of estrogenic activity from synthetic water due to their strong adsorption on the surface of TiO(2). However, only a weak impact was noted during photocatalytic removal of estrogenic activity from secondary effluent with these ions added, since the presence of DOM in real wastewater played a more important role in inhibiting photocatalytic removal of estrogenic activity than inorganic ions. By investigating the effect of different DOM fractions on photocatalytic removal of estrogenic activity, polar compounds (PC) were found to cause a temporary increase in estrogenic activity during TiO(2) photocatalysis. Fluorescence spectroscopy and molecular weight (MW) analysis on secondary effluent spiked with PC during TiO(2) photocatalysis suggest that large MW organic matter (>4.5kDa) in secondary effluent, such as humic/fulvic acid, not only could play an important role in inhibiting photocatalytic removal of estrogenic activity but also is responsible for the temporary increase in estrogenic activity during the same process.

  3. [Endocrine-metabolic adjustments during Ramadan fasting in young athletes].

    PubMed

    Guerrero-Morilla, Raúl; Ramírez-Rodrigo, Jesús; Ruiz-Villaverde, Gonzalo; Sánchez-Caravaca, Ma Angeles; Pérez-Moreno, Barbara Alejandra; Villaverde-Gutiérrez, Carmen

    2013-03-01

    The Islamic precept of R implies important physiological modifications due to the hydric and dietetic restrictions along a whole month plus a day, all of which have a crucial repercussion over the physical and intellectual performance of Muslims, particularly in occidental societies, in which there is no hour readjustments for daily activities. Among the imposed modifications by Ramadan in daily habits, intermittent fasting along day and night causes adaptation mechanisms to optimize the energy consumption. The objective of this study was to analyze the metabolic-endocrine changes that happen during daily working hours, along the month of fasting in young subjects who have to continue their usual activities and sport training. Ten young muslim subjects, male, healthy, set to sport training, ages in between 18 and 25 who completed Ramadan. Plasma biochemical and hormonal parameters were analyzed in plasma, a week before Ramadan, in the first and fourth of the fasting month and a week after conclusion. During Ramadan, have been observed a drop of biochemical parameters along daytime, especially those related to glycemia, being these changes stronger in the first week. The concentration of cortisol found to be significantly high during the whole month as a consequence of adaptation to the change of circadian secretion rhythms. Ramadan obliges subject's organisms to readjust their endocrine and metabolic system in order to preserve the energetic efficiency during daytime. This auto control becomes more efficient as long as the month advances due to physiological adaptations. PMID:24171224

  4. Ethical aspects of organ donation activities.

    PubMed

    Stephan, Antoine; Barbari, Antoine; Younan, Farida

    2007-12-01

    Renal transplant remains the treatment of choice for patients with end-stage renal disease. Human organs can be harvested from 2 main sources: living and deceased donors. Preference should be given to deceased-donor transplants since they represent the only source of organs for several nonrenal solid-organ transplants and the only modality where there is no risk to the donor. Unfortunately, even the most well-developed deceased-donor program (eg, the Spanish program) can barely cover 50% of its waiting list because the demand for deceased-donor organs far exceeds supply. The success of transplant surgery has created a waiting list dilemma. Despite all efforts, deceased-donor donation cannot meet current needs and therefore, living donation demands serious consideration. This is supported by the fact that the risk to live donors is minimal, graft survival is significantly better than that of deceased-donor kidneys regardless of HLA matching, and professional ethical philosophers have fewer difficulties with voluntary living donations than with the removal of an organ from a cadaver. This is especially true in our region. Living-related donation has always been acceptable ethically. It is, however, limited by the number of willing and qualified donors, the high incidence of familial renal diseases, and donor coercion (especially in our area). Living-unrelated donation increases the availability of donors, decreases the chances of coercion, and eliminates the problem of consanguinity. It raises, however, the ethical issues of commercialism, transplant tourism, and organ trafficking. The arguments for and against living-unrelated donation are innumerable. They have been the subject of several international forums and have raised endless discussions. We have set long ago a series of rules and regulations that are in close agreement with the recent Amsterdam and Kuwait resolutions. We have been continually modifying them over the last 15 years to try to implement our

  5. [Hypotension from endocrine origin].

    PubMed

    Vantyghem, Marie-Christine; Douillard, Claire; Balavoine, Anne-Sophie

    2012-11-01

    Hypotension is defined by a low blood pressure either permanently or only in upright posture (orthostatic hypotension). In contrast to hypertension, there is no threshold defining hypotension. The occurrence of symptoms for systolic and diastolic measurements respectively below 90 and 60 mm Hg establishes the diagnosis. Every acute hypotensive event should suggest shock, adrenal failure or an iatrogenic cause. Chronic hypotension from endocrine origin may be linked to adrenal failure from adrenal or central origin, isolated hypoaldosteronism, pseudohypoaldosteronism, pheochromocytoma, neuro-endocrine tumors (carcinoïd syndrome) or diabetic dysautonomia. Hypotension related to hypoaldosteronism associates low blood sodium and above all high blood potassium levels. They are generally classified according to their primary (hyperreninism) or secondary (hyporeninism) adrenal origin. Isolated primary hypoaldosteronisms are rare in adults (intensive care unit, selective injury of the glomerulosa area) and in children (aldosterone synthase deficiency). Isolated secondary hypoaldosteronism is related to mellitus diabetes complicated with dysautonomia, kidney failure, age, iatrogenic factors, and HIV infections. In both cases, they can be associated to glucocorticoid insufficiency from primary adrenal origin (adrenal failure of various origins with hyperreninism, among which congenital 21 hydroxylase deficiency with salt loss) or from central origin (hypopituitarism with hypo-reninism). Pseudohypoaldosteronisms are linked to congenital (type 1 pseudohypoaldosteronism) or acquired states of resistance to aldosterone. Acquired salt losses from enteric (total colectomy with ileostomy) or renal (interstitial nephropathy, Bartter and Gitelman syndromes…) origin might be responsible for hypotension and are associated with hyperreninism-hyperaldosteronism. Hypotension is a rare manifestation of pheochromocytomas, especially during surgical removal when the patient has not been

  6. Diabetic and endocrine emergencies

    PubMed Central

    Kearney, T; Dang, C

    2007-01-01

    Endocrine emergencies constitute only a small percentage of the emergency workload of general doctors, comprising about 1.5% of all hospital admission in England in 2004–5. Most of these are diabetes related with the remaining conditions totalling a few hundred cases at most. Hence any individual doctor might not have sufficient exposure to be confident in their management. This review discusses the management of diabetic ketoacidosis, hyperosmolar hyperglycaemic state, hypoglycaemia, hypercalcaemia, thyroid storm, myxoedema coma, acute adrenal insufficiency, phaeochromocytoma hypertensive crisis and pituitary apoplexy in the adult population. PMID:17308209

  7. [Endocrine disorders and osteoporosis].

    PubMed

    Kinoshita, Yuka

    2015-10-01

    Secondary osteoporosis is a bone disease characterized by decreased bone mass that predisposes fractures due to underlying disorders or medication. Disorders of the endocrine system, such as primary hyperparathyroidism, hyperthyroidism, hypogonadism, growth hormone deficiency, Cushing's syndrome, and anorexia nervosa frequently cause secondary osteoporosis. In those diseases, hormone excess or deficiency affects functions of osteoblasts, osteocyte, and osteoclasts, leading to aberrant bone remodeling. Bisphosphonates are the first-choice pharmacological agents for fracture prevention in most patients with secondary osteoporosis along with treatment of the underlying disease. PMID:26529938

  8. Development and Characterization of a Human Reporter Cell Line for the Assessment of Thyroid Receptor Transcriptional Activity: A Case of Organotin Endocrine Disruptors.

    PubMed

    Illés, Peter; Brtko, Július; Dvořák, Zdeněk

    2015-08-12

    We developed and characterized the human luciferase reporter cell line PZ-TR for the assessment of thyroid receptor (TR) transcriptional activity. Triiodothyronine (T3) induced luciferase activity in a dose-dependent manner, and the sensitivity of assay allowed for the detection of nanomolar T3 concentrations. The luciferase activity was induced by a maximum of (2.42 ± 0.14)-(2.73 ± 0.23)-fold after 24 h of exposure to 10 nM T3. We did not observe a nonspecific induction of luciferase activity by other steroid hormones and VDR ligands, with the exception of partial activation by retinoic acids. Cryopreservation of PZ-TR cells did not influence their functionality, responsivity to T3, or cell morphology, even after long-term cultivation. PZ-TR cells were used to evaluate the effects of organic tin compounds on TR. We found that the tributyltin and triphenyltin derivatives induced luciferase activity and that application of organotins in combination with T3 enhanced the effect of T3. These findings indicate that organic tin compounds have potential to interfere with TR-mediated regulation of gene expression and influence the physiological activity of thyroid hormones. PMID:26208032

  9. Bariatric Surgery and the Endocrine System

    MedlinePlus

    ... Endocrine System Fact Sheet Bariatric Surgery and the Endocrine System February, 2012 Download PDFs English Espanol Editors John ... could have both benefits and risks for your endocrine system—the network of glands that produce, store, and ...

  10. Sun lotion chemicals as endocrine disruptors.

    PubMed

    Maipas, Sotirios; Nicolopoulou-Stamati, Polyxeni

    2015-01-01

    Ultraviolet solar radiation is a well-known environmental health risk factor and the use of sun lotions is encouraged to achieve protection mainly from skin cancer. Sun lotions are cosmetic commercial products that combine active and inactive ingredients and many of these are associated with health problems, including allergic reactions and endocrine disorders. This review focuses on their ability to cause endocrine and reproductive impairments, with emphasis laid on the active ingredients (common and less common UV filters). In vitro and in vivo studies have demonstrated their ability to show oestrogenic/anti-oestrogenic and androgenic/anti-androgenic activity. Many ingredients affect the oestrous cycle, spermatogenesis, sexual behaviour, fertility and other reproductive parameters in experimental animals. Their presence in aquatic environments may reveal a new emerging environmental hazard. PMID:25885102

  11. Sun lotion chemicals as endocrine disruptors.

    PubMed

    Maipas, Sotirios; Nicolopoulou-Stamati, Polyxeni

    2015-01-01

    Ultraviolet solar radiation is a well-known environmental health risk factor and the use of sun lotions is encouraged to achieve protection mainly from skin cancer. Sun lotions are cosmetic commercial products that combine active and inactive ingredients and many of these are associated with health problems, including allergic reactions and endocrine disorders. This review focuses on their ability to cause endocrine and reproductive impairments, with emphasis laid on the active ingredients (common and less common UV filters). In vitro and in vivo studies have demonstrated their ability to show oestrogenic/anti-oestrogenic and androgenic/anti-androgenic activity. Many ingredients affect the oestrous cycle, spermatogenesis, sexual behaviour, fertility and other reproductive parameters in experimental animals. Their presence in aquatic environments may reveal a new emerging environmental hazard.

  12. Male infertility. 3. Endocrine causes.

    PubMed

    McNally, M R

    1987-02-01

    Endocrine causes of male infertility range from easily manageable disorders such as hypothyroidism to complex problems such as pituitary tumors. Proper management requires a thorough understanding of the hypothalamic-pituitary-testicular axis. Hormonal evaluation is performed only when the patient's history and results of physical examination indicate an endocrine problem. With proper identification and treatment, most of these problems can be successfully managed.

  13. Trauma and the endocrine system.

    PubMed

    Mesquita, Joana; Varela, Ana; Medina, José Luís

    2010-12-01

    The endocrine system may be the target of different types of trauma with varied consequences. The present article discusses trauma of the hypothalamic-pituitary axes, adrenal glands, gonads, and pancreas. In addition to changes in circulating hormone levels due to direct injury to these structures, there may be an endocrine response in the context of the stress caused by the trauma.

  14. Active Pharmaceutical Ingredients and Aquatic Organisms

    EPA Science Inventory

    The presence of active pharmaceuticals ingredients (APIs) in aquatic systems in recent years has led to a burgeoning literature examining environmental occurrence, fate, effects, risk assessment, and treatability of these compounds. Although APIs have received much attention as ...

  15. Application of Molecular Pathology in Endocrine Pathology.

    PubMed

    Linke, Ebru Serinsoz; Tezel, Gaye Güler

    2015-01-01

    Rapid growth in knowledge of cell and molecular biology led to the increased usage of molecular techniques in anatomical pathology. This is also due to the advances achieved in the techniques introduced in the last few years which are less laborious as compared to the techniques used at the beginning of the "molecular era". The initial assays were also very expensive and were not performed except for selected centers. Moreover, the clinicians were not sure how to make use of the accumulating molecular information. That situation has also changed and molecular techniques are being performed in a wide variety of medical settings which also has a reflection on the endocrine system pathology among other organ systems. This review will provide an update of genetic changes observed in different endocrine system pathologies and their diagnostic, therapeutic and prognostic values.

  16. The unique endocrine milieu of the fetus.

    PubMed Central

    Fisher, D A

    1986-01-01

    Table II summarizes in tabular form the major features of the fetal endocrine milieu discussed in the foregoing pages. The mammalian fetus develops in an environment where respiration, alimentation, and excretory functions are provided by the placenta. Fetal tissue metabolism is oriented largely to anabolism; body temperature is modulated by maternal metabolism, and fetal tissue thermogenesis is maintained at a basal level. Tissue and organ growth appear to be regulated by growth factors which probably function by autocrine or paracrine mechanisms during most of gestation (72, 146-148). In this milieu conventional endocrine control systems are largely redundant, and other transient systems more appropriate to the intrauterine environment have evolved. We have developed some insights into these systems, but much more information is necessary before we can truly understand this fascinating environment. PMID:3018041

  17. FOXO factors and breast cancer: outfoxing endocrine resistance.

    PubMed

    Bullock, M

    2016-02-01

    The majority of metastatic breast cancers cannot be cured and present a major public health problem worldwide. Approximately 70% of breast cancers express the estrogen receptor, and endocrine-based therapies have significantly improved patient outcomes. However, the development of endocrine resistance is extremely common. Understanding the molecular pathways that regulate the hormone sensitivity of breast cancer cells is important to improving the efficacy of endocrine therapy. It is becoming clearer that the PI3K-AKT-forkhead box O (FOXO) signaling axis is a key player in the hormone-independent growth of many breast cancers. Constitutive PI3K-AKT pathway activation, a driver of breast cancer growth, causes down-regulation of FOXO tumor suppressor functions. This review will summarize what is currently known about the role of FOXOs in endocrine-resistance mechanisms. It will also suggest potential therapeutic strategies for the restoration of normal FOXO transcriptional activity.

  18. Nonoxidative removal of organics in the activated sludge process

    PubMed Central

    Modin, Oskar; Persson, Frank; Wilén, Britt-Marie; Hermansson, Malte

    2016-01-01

    ABSTRACT The activated sludge process is commonly used to treat wastewater by aerobic oxidation of organic pollutants into carbon dioxide and water. However, several nonoxidative mechanisms can also contribute to removal of organics. Sorption onto activated sludge can remove a large fraction of the colloidal and particulate wastewater organics. Intracellular storage of, e.g., polyhydroxyalkanoates (PHA), triacylglycerides (TAG), or wax esters can convert wastewater organics into precursors for high-value products. Recently, several environmental, economic, and technological drivers have stimulated research on nonoxidative removal of organics for wastewater treatment. In this paper, we review these nonoxidative removal mechanisms as well as the existing and emerging process configurations that make use of them for wastewater treatment. Better utilization of nonoxidative processes in activated sludge could reduce the wasteful aerobic oxidation of organic compounds and lead to more resource-efficient wastewater treatment plants. PMID:27453679

  19. Organized Subsurface Flows near Active Regions

    NASA Astrophysics Data System (ADS)

    Haber, D. A.; Hindman, B. W.; Toomre, J.; Thompson, M. J.

    2004-04-01

    Local helioseismic techniques, such as ring analysis and time-distance helioseismology, have already shown that large-scale flows near the surface converge towards major active regions. Ring analysis has further demonstrated that at greater depths some active regions exhibit strong outflows. A critique leveled at the ring-analysis results is that the Regularized Least Squares (RLS) inversion kernels on which they are based have negative sidelobes near the surface. Such sidelobes could result in a surface inflow being misidentified as a diverging outflow at depth. In this paper we show that the Optimally Located Averages (OLA) inversion technique, which produces kernels without significant sidelobes, generates flows markedly similar to the RLS results. Active regions are universally zones of convergence near the surface, while large complexes evince strong outflows deeper down.

  20. Structural complexities in the active layers of organic electronics.

    PubMed

    Lee, Stephanie S; Loo, Yueh-Lin

    2010-01-01

    The field of organic electronics has progressed rapidly in recent years. However, understanding the direct structure-function relationships between the morphology in electrically active layers and the performance of devices composed of these materials has proven difficult. The morphology of active layers in organic electronics is inherently complex, with heterogeneities existing across multiple length scales, from subnanometer to micron and millimeter range. A major challenge still facing the organic electronics community is understanding how the morphology across all of the length scales in active layers collectively determines the device performance of organic electronics. In this review we highlight experiments that have contributed to the elucidation of structure-function relationships in organic electronics and also point to areas in which knowledge of such relationships is still lacking. Such knowledge will lead to the ability to select active materials on the basis of their inherent properties for the fabrication of devices with prespecified characteristics.

  1. Targeted toxicological testing to investigate the role of endocrine disrupters in puberty disorders.

    PubMed

    Maranghi, Francesca; Mantovani, Alberto

    2012-06-01

    Puberty is a process regulated by the endocrine system which physiological onset is poorly understood. Factors potentially leading to the disruption of this system may seriously affect the reproductive function development. Altered puberty onset can be an unspecific consequence of general toxicity in juvenile rodents; however, several toxicological studies indicate potential effects of specific substances on puberty development. In particular, the exposure to endocrine disrupters (ED) showing (anti)estrogenic, (anti)androgenic activity or interaction with hypothalamic-pituitary-gonadal (HPG) axis is considered biologically plausible and deserving attention. Risk assessment agencies call for data on children effects for their specific vulnerability or specific exposure situations. On the other hand, no international effort is foreseen to develop robust tools for characterizing chemical hazards in the immature organisms. For some chemicals the available data might be sufficient to trigger precautionary measures but a sound risk analysis needs an interdisciplinary integration between human medicine and experimental toxicology.

  2. Endocrine effects of the herbicide linuron on the American Goldfinch (Carduelis tristis)

    USGS Publications Warehouse

    Sughrue, K.M.; Brittingham, M.C.; French, J.B.

    2008-01-01

    Certain contaminants alter normal physiological function, morphology, and behavior of exposed organisms through an endocrine mechanism. We evaluated how the herbicide linuron, an endocrine-active compound, affects physiological parameters and secondary sex characteristics of the American Goldfinch (Carduelis tristis). When administered at relatively low doses (control, 1.0, 4.0, and 16.0 mu g linuron per gram of body mass per day), linuron delayed prealternate molt progression in a dose-dependent manner. At the high dose level, linuron exposure lowered hematocrit and female plasma thyroxine concentrations and increased body mass. Neither plasma testosterone concentrations nor the color of plumage or integument of birds in the treatment groups were different from those of the control group. Overall, the physiological effects that were measured suggested disruption of thyroid function. These results highlight the importance of continual monitoring of avian populations for potential effects of exposure to pesticides and other chemicals at sublethal concentrations.

  3. t4 workshop report--lessons learned, challenges, and opportunities: the U.S. Endocrine Disruptor Screening Program.

    PubMed

    Juberg, Daland R; Borghoff, Susan J; Becker, Richard A; Casey, Warren; Hartung, Thomas; Holsapple, Michael P; Marty, M Sue; Mihaich, Ellen M; Van Der Kraak, Glen; Wade, Michael G; Willett, Catherine E; Andersen, Melvin E; Borgert, Christopher J; Coady, Katherine K; Dourson, Michael L; Fowle, John R; Gray, L Earl; Lamb, James C; Ortego, Lisa S; Schug, Thaddeus T; Toole, Colleen M; Zorrilla, Leah M; Kroner, Oliver L; Patterson, Jacqueline; Rinckel, Lori A; Jones, Brett R

    2014-01-01

    In 1996, the U.S. Congress passed the Food Quality Protection Act and amended the Safe Drinking Water Act (SDWA) requiring the U.S. Environmental Protection Agency (EPA) to implement a screening program to investigate the potential of pesticide chemicals and drinking water contaminants to adversely affect endocrine pathways. Consequently, the EPA launched the Endocrine Disruptor Screening Program (EDSP) to develop and validate estrogen, androgen, and thyroid (EAT) pathway screening assays and to produce standardized and harmonized test guidelines for regulatory application. In 2009, the EPA issued the first set of test orders for EDSP screening and a total of 50 pesticide actives and 2 inert ingredients have been evaluated using the battery of EDSP Tier 1 screening assays (i.e., five in vitro assays and six in vivo assays). To provide a framework for retrospective analysis of the data generated and to collect the insight of multiple stakeholders involved in the testing, more than 240 scientists from government, industry, academia, and non-profit organizations recently participated in a workshop titled "Lessons Learned, Challenges, and Opportunities: The U.S. Endocrine Disruptor Screening Program." The workshop focused on the science and experience to date and was organized into three focal sessions: (a) Performance of the EDSP Tier 1 Screening Assays for Estrogen, Androgen, and Thyroid Pathways; (b) Practical Applications of Tier 1 Data; and (c) Indications and Opportunities for Future Endocrine Testing. A number of key learnings and recommendations related to future EDSP evaluations emanated from the collective sessions. PMID:24114257

  4. Role of zinc and alpha2 macroglobulin on thymic endocrine activity and on peripheral immune efficiency (natural killer activity and interleukin 2) in cervical carcinoma.

    PubMed

    Mocchegiani, E; Ciavattini, A; Santarelli, L; Tibaldi, A; Muzzioli, M; Bonazzi, P; Giacconi, R; Fabris, N; Garzetti, G G

    1999-01-01

    Decreased natural killer (NK) activity as well as interleukin 2 (IL-2) are risk factors for the progression of cervical carcinoma. NK activity and IL-2 may be thymus controlled. Plasma levels of active thymulin, a zinc-dependent thymic hormone (ZnFTS), are reduced in cancer because of the low peripheral zinc bioavailability. Zinc and thymulin are relevant for normal immune functions. Alpha2-macroglobulin is an inhibitor of matrix metalloproteases (MMPs) against invasive tumour proliferation. Because alpha2-macroglobulin has a binding affinity (Kd) for zinc that is higher than does thymulin, it may play a key role in immune efficiency in cancer. Plasma samples of 22 patients (age range 35-60 years) with locally advanced squamous cervical carcinoma and with FIGO stage Ib2-IIb were examined. They showed reduced active thymulin, decreased NK activity and IL-2 production, increased soluble IL-2 receptor (sIL-2R) and augmented alpha2-macroglobulin in the circulation, whereas plasma zinc levels were within the normal range for age. Significant positive correlations were found between zinc or active thymulin and alpha2-macroglobulin (r = 0.75, P < 0.01, r = 0.78, P < 0.01, respectively) in cancer patients. In vitro zinc increases IL-2 production from peripheral blood mononuclear cells (PBMCs) of cancer patients. These data suggest that an increase in alpha2-macroglobulin, which competes with thymulin for zinc binding, may be involved in causing a thymulin deficit with a consequent decrease of IL-2 and NK cytotoxicity. Thus, physiological zinc treatment in cervical carcinoma maybe restores impaired central and peripheral immune efficiency.

  5. Role of zinc and α2macroglobulin on thymic endocrine activity and on peripheral immune efficiency (natural killer activity and interleukin 2) in cervical carcinoma

    PubMed Central

    Mocchegiani, E; Ciavattini, A; Santarelli, L; Tibaldi, A; Muzzioli, M; Bonazzi, P; Giacconi, R; Fabris, N; Garzetti, G G

    1999-01-01

    Decreased natural killer (NK) activity as well as interleukin 2 (IL-2) are risk factors for the progression of cervical carcinoma. NK activity and IL-2 may be thymus controlled. Plasma levels of active thymulin, a zinc-dependent thymic hormone (ZnFTS), are reduced in cancer because of the low peripheral zinc bioavailability. Zinc and thymulin are relevant for normal immune functions. α2-Macroglobulin is an inhibitor of matrix metalloproteases (MMPs) against invasive tumour proliferation. Because α2-macroglobulin has a binding affinity (Kd) for zinc that is higher than does thymulin, it may play a key role in immune efficiency in cancer. Plasma samples of 22 patients (age range 35–60 years) with locally advanced squamous cervical carcinoma and with FIGO stage Ib2–IIb were examined. They showed reduced active thymulin, decreased NK activity and IL-2 production, increased soluble IL-2 receptor (sIL-2R) and augmented α2-macroglobulin in the circulation, whereas plasma zinc levels were within the normal range for age. Significant positive correlations were found between zinc or active thymulin and α2-macroglobulin (r = 0.75, P< 0.01, r = 0.78, P< 0.01, respectively) in cancer patients. In vitro zinc increases IL-2 production from peripheral blood mononuclear cells (PBMCs) of cancer patients. These data suggest that an increase in α2-macroglobulin, which competes with thymulin for zinc binding, may be involved in causing a thymulin deficit with a consequent decrease of IL-2 and NK cytotoxicity. Thus, physiological zinc treatment in cervical carcinoma maybe restores impaired central and peripheral immune efficiency. © 1999 Cancer Research Campaign PMID:9888464

  6. [Effects of different fertilizer application on soil active organic carbon].

    PubMed

    Zhang, Rui; Zhang, Gui-Long; Ji, Yan-Yan; Li, Gang; Chang, Hong; Yang, Dian-Lin

    2013-01-01

    The variation characteristics of the content and components of soil active organic carbon under different fertilizer application were investigated in samples of calcareous fluvo-aquic soil from a field experiment growing winter wheat and summer maize in rotation in the North China Plain. The results showed that RF (recommended fertilization), CF (conventional fertilization) and NPK (mineral fertilizer alone) significantly increased the content of soil dissolved organic carbon and easily oxidized organic carbon by 24.92-38.63 mg x kg(-1) and 0.94-0.58 mg x kg(-1) respectively compared to CK (unfertilized control). The soil dissolved organic carbon content under OM (organic manure) increased greater than those under NPK and single fertilization, soil easily oxidized organic carbon content under OM and NPK increased greater than that under single chemical fertilization. OM and NPK showed no significant role in promoting the soil microbial biomass carbon, but combined application of OM and NPK significantly increased the soil microbial biomass carbon content by 36.06% and 20.69%, respectively. Soil easily oxidized organic carbon, dissolved organic carbon and microbial biomass carbon accounted for 8.41% - 14.83%, 0.47% - 0.70% and 0.89% - 1.20% of the total organic carbon (TOC), respectively. According to the results, the fertilizer application significantly increased the proportion of soil dissolved organic carbon and easily oxidized organic carbon, but there was no significant difference in the increasing extent of dissolved organic carbon. The RF and CF increased the proportion of soil easily oxidized organic carbon greater than OM or NPK, and significantly increased the proportion of microbial biomass carbon. OM or RF had no significant effect on the proportion of microbial biomass carbon. Therefore, in the field experiment, appropriate application of organic manure and chemical fertilizers played an important role for the increase of soil active organic carbon

  7. [Effects of different fertilizer application on soil active organic carbon].

    PubMed

    Zhang, Rui; Zhang, Gui-Long; Ji, Yan-Yan; Li, Gang; Chang, Hong; Yang, Dian-Lin

    2013-01-01

    The variation characteristics of the content and components of soil active organic carbon under different fertilizer application were investigated in samples of calcareous fluvo-aquic soil from a field experiment growing winter wheat and summer maize in rotation in the North China Plain. The results showed that RF (recommended fertilization), CF (conventional fertilization) and NPK (mineral fertilizer alone) significantly increased the content of soil dissolved organic carbon and easily oxidized organic carbon by 24.92-38.63 mg x kg(-1) and 0.94-0.58 mg x kg(-1) respectively compared to CK (unfertilized control). The soil dissolved organic carbon content under OM (organic manure) increased greater than those under NPK and single fertilization, soil easily oxidized organic carbon content under OM and NPK increased greater than that under single chemical fertilization. OM and NPK showed no significant role in promoting the soil microbial biomass carbon, but combined application of OM and NPK significantly increased the soil microbial biomass carbon content by 36.06% and 20.69%, respectively. Soil easily oxidized organic carbon, dissolved organic carbon and microbial biomass carbon accounted for 8.41% - 14.83%, 0.47% - 0.70% and 0.89% - 1.20% of the total organic carbon (TOC), respectively. According to the results, the fertilizer application significantly increased the proportion of soil dissolved organic carbon and easily oxidized organic carbon, but there was no significant difference in the increasing extent of dissolved organic carbon. The RF and CF increased the proportion of soil easily oxidized organic carbon greater than OM or NPK, and significantly increased the proportion of microbial biomass carbon. OM or RF had no significant effect on the proportion of microbial biomass carbon. Therefore, in the field experiment, appropriate application of organic manure and chemical fertilizers played an important role for the increase of soil active organic carbon

  8. Endocrine-like Signaling in Cnidarians: Current Understanding and Implications for Ecophysiology.

    PubMed

    Tarrant, Ann M

    2005-01-01

    The vertebrate endocrine system is well-characterized, with many reports of disruption by environmental chemicals. In contrast, cnidarians are less compartmentalized, physiological regulation is poorly understood, and the potential for disruption is unknown. Endocrine-like activity has not been systematically studied in cnidarians, but several classical vertebrate hormones (e.g., steroids, iodinated organic compounds, neuropeptides, and indoleamines) have been identified in cnidarian tissues. Investigators have made progress in identifying putative bioregulatory molecules in cnidarians, and testing the effects of these individual compounds. Less progress has been made in elucidating signaling pathways. For example, putative gonadotropin-releasing hormone and sex steroids have been identified in cnidarian tissues, but it is unknown whether these compounds are components of a larger signal cascade comparable to the vertebrate hypothalamic-pituitary-gonadal axis. Further, while sex steroids and iodinated organic compounds may help to regulate cnidarian physiology, the mechanisms of action are unknown. Homologs to the vertebrate steroid and thyroid receptors have not been identified in cnidarians, so more research is needed to understand the mechanisms of endocrine-like signaling in cnidarians. Elucidation of cnidarian regulatory pathways will provide insight into evolution of hormonal signaling. These studies will also improve understanding of how cnidarians respond to environmental cues and will provide a basis to investigate disruption of physiological processes by physical and chemical stressors.

  9. Activated persulfate for organic chemical degradation: A review.

    PubMed

    Matzek, Laura W; Carter, Kimberly E

    2016-05-01

    Activated persulfate reactions have widespread application for groundwater and environmental remediation, as many of these reactions involve destruction of environmental contaminants. Within the last five years, knowledge of activated persulfate degradation reactions has grown to include novel means of activating persulfate for enhanced removal of organic species. These current studies cover a long list of organic analytes, including pharmaceuticals, pesticides, halogenated compounds and dyes. An extensive review of recently published experimental parameters and results for the destruction of organic compounds via activated persulfate is presented. Focus is placed on emerging methodologies and manipulation of traditional activation techniques. Knowledge gaps are identified and discussed, as despite the number of publications on this subject, more broad-reaching guidelines are needed for optimizing applications of activated persulfate in water treatment.

  10. Endocrine causes of calcium disorders.

    PubMed

    Greco, Deborah S

    2012-11-01

    Endocrine diseases that may cause hypercalcemia and hypocalcemia include hyperparathyroidism, hypoparathyroidism, thyroid disorders, hyperadrenocorticism, hypoadrenocorticism, and less commonly pheochromocytoma and multiple endocrine neoplasias. The differential diagnosis of hypercalcemia may include malignancy (lymphoma, anal sac carcinoma, and squamous cell carcinoma), hyperparathyroidism, vitamin D intoxication, chronic renal disease, hypoadrenocorticism, granulomatous disorders, osteolysis, or spurious causes. Hypocalcemia may be caused by puerperal tetany, pancreatitis, intestinal malabsorption, ethlyene glycol intoxication, acute renal failure, hypopararthyroidism, hypovitaminosis D, hypomagnesemia, and low albumin. This article focuses on the endocrine causes of calcium imbalance and provides diagnostic and therapeutic guidelines for identifying the cause of hypercalcemia and hypocalcemia in veterinary patients.

  11. Computational model of the fathead minnow hypothalamic-pituitary-gonadal axis: Incorporating protein synthesis in improving predictability of responses to endocrine active chemicals.

    PubMed

    Breen, Miyuki; Villeneuve, Daniel L; Ankley, Gerald T; Bencic, David; Breen, Michael S; Watanabe, Karen H; Lloyd, Alun L; Conolly, Rory B

    2016-01-01

    There is international concern about chemicals that alter endocrine system function in humans and/or wildlife and subsequently cause adverse effects. We previously developed a mechanistic computational model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows exposed to a model aromatase inhibitor, fadrozole (FAD), to predict dose-response and time-course behaviors for apical reproductive endpoints. Initial efforts to develop a computational model describing adaptive responses to endocrine stress providing good fits to empirical plasma 17β-estradiol (E2) data in exposed fish were only partially successful, which suggests that additional regulatory biology processes need to be considered. In this study, we addressed short-comings of the previous model by incorporating additional details concerning CYP19A (aromatase) protein synthesis. Predictions based on the revised model were evaluated using plasma E2 concentrations and ovarian cytochrome P450 (CYP) 19A aromatase mRNA data from two fathead minnow time-course experiments with FAD, as well as from a third 4-day study. The extended model provides better fits to measured E2 time-course concentrations, and the model accurately predicts CYP19A mRNA fold changes and plasma E2 dose-response from the 4-d concentration-response study. This study suggests that aromatase protein synthesis is an important process in the biological system to model the effects of FAD exposure.

  12. Short-term fish reproduction assays with methyl tertiary butyl ether with zebrafish and fathead minnow: Implications for evaluation of potential for endocrine activity.

    PubMed

    Mihaich, Ellen; Erler, Steffen; Le Blanc, Gerald; Gallagher, Sean

    2015-09-01

    The authors report on short-term fish reproduction assays in zebrafish and fathead minnow conducted to examine the potential for methyl tertiary butyl ether (MTBE) to cause effects on the endocrine system. Both studies were performed under good laboratory practice and in accordance with Organisation for Economic Co-operation and Development and US Environmental Protection Agency test guidelines. The results of the first study demonstrated that exposure to a high test concentration (147 mg/L) of MTBE impaired reproductive output of female zebrafish, evident by a reduction in fecundity. Based on the endpoints evaluated in the present study however, there was no supporting evidence to indicate that this effect was caused by disruption of or interaction with the endocrine system. In the second study, fathead minnows exposed to a wider but lower range of test concentrations showed no effects on any reproductive parameter of male or female fish, at the maximum recommended testing concentration of 100 mg/L (62 mg/L measured). The results of these 2 guideline studies indicate that MTBE does not interact with the hypothalamic-pituitary-gonadal axis of zebrafish or fathead minnow. PMID:25866897

  13. Short-term fish reproduction assays with methyl tertiary butyl ether with zebrafish and fathead minnow: Implications for evaluation of potential for endocrine activity.

    PubMed

    Mihaich, Ellen; Erler, Steffen; Le Blanc, Gerald; Gallagher, Sean

    2015-09-01

    The authors report on short-term fish reproduction assays in zebrafish and fathead minnow conducted to examine the potential for methyl tertiary butyl ether (MTBE) to cause effects on the endocrine system. Both studies were performed under good laboratory practice and in accordance with Organisation for Economic Co-operation and Development and US Environmental Protection Agency test guidelines. The results of the first study demonstrated that exposure to a high test concentration (147 mg/L) of MTBE impaired reproductive output of female zebrafish, evident by a reduction in fecundity. Based on the endpoints evaluated in the present study however, there was no supporting evidence to indicate that this effect was caused by disruption of or interaction with the endocrine system. In the second study, fathead minnows exposed to a wider but lower range of test concentrations showed no effects on any reproductive parameter of male or female fish, at the maximum recommended testing concentration of 100 mg/L (62 mg/L measured). The results of these 2 guideline studies indicate that MTBE does not interact with the hypothalamic-pituitary-gonadal axis of zebrafish or fathead minnow.

  14. Endocrine Proxies Can Simplify Endocrine Complexity to Enable Evolutionary Prediction.

    PubMed

    Davidowitz, Goggy

    2016-08-01

    It is well understood that much of evolutionary change is mediated through the endocrine system with growing interest to identify how this occurs. This however, causes a conflict of sorts. To understand endocrine mechanism, a focus on detail is required. In contrast, to understand evolutionary change, reduction to a few key traits is essential. Endocrine proxies, measurable traits that accurately reflect specific hormonal titers or the timing of specific hormonal events, can reduce endocrine complexity to a few traits that enable predictions of how the endocrine system regulates evolutionary change. In the tobacco hornworm (Manduca sexta, Sphingidae), three endocrine proxies, measured on 5470 individuals, were used to test explicit predictions of how the endocrine system regulates the response to 10 generations of simultaneous selection on body size and development time. The critical weight (CW) reflects the variation in the cessation of juvenile hormone (JH) secretion in the last larval instar, the interval to cessation of growth (ICG) reflects the variation in prothoracicotropic hormone and 20-hydroxyecdysone (20E). Growth rate (GR) reflects the nutrient signaling pathways, primarily the insulin and TOR This is a standard identity similar to DNA signaling pathways. These three endocrine proxies explained 99% and 93% of the variation in body size and development time, respectively, following the 10 generations of simultaneous selection. When the two focal traits, body size and development time, were selected in the same direction, both to either increase or both to decrease, the response to selection was determined primarily by the CW and the ICG, proxies for the developmental hormones JH and 20E, and constrained by GR. In contrast, when the two focal traits were selected in opposite directions, one to increase and the other to decrease, the response to selection was determined primarily by the insulin and TOR signaling pathways as measured by their proxy, GR, and

  15. Endocrine Proxies Can Simplify Endocrine Complexity to Enable Evolutionary Prediction.

    PubMed

    Davidowitz, Goggy

    2016-08-01

    It is well understood that much of evolutionary change is mediated through the endocrine system with growing interest to identify how this occurs. This however, causes a conflict of sorts. To understand endocrine mechanism, a focus on detail is required. In contrast, to understand evolutionary change, reduction to a few key traits is essential. Endocrine proxies, measurable traits that accurately reflect specific hormonal titers or the timing of specific hormonal events, can reduce endocrine complexity to a few traits that enable predictions of how the endocrine system regulates evolutionary change. In the tobacco hornworm (Manduca sexta, Sphingidae), three endocrine proxies, measured on 5470 individuals, were used to test explicit predictions of how the endocrine system regulates the response to 10 generations of simultaneous selection on body size and development time. The critical weight (CW) reflects the variation in the cessation of juvenile hormone (JH) secretion in the last larval instar, the interval to cessation of growth (ICG) reflects the variation in prothoracicotropic hormone and 20-hydroxyecdysone (20E). Growth rate (GR) reflects the nutrient signaling pathways, primarily the insulin and TOR This is a standard identity similar to DNA signaling pathways. These three endocrine proxies explained 99% and 93% of the variation in body size and development time, respectively, following the 10 generations of simultaneous selection. When the two focal traits, body size and development time, were selected in the same direction, both to either increase or both to decrease, the response to selection was determined primarily by the CW and the ICG, proxies for the developmental hormones JH and 20E, and constrained by GR. In contrast, when the two focal traits were selected in opposite directions, one to increase and the other to decrease, the response to selection was determined primarily by the insulin and TOR signaling pathways as measured by their proxy, GR, and

  16. Alliance Affiliate Activities: Non-Governmental Organizations in Environmental Education.

    ERIC Educational Resources Information Center

    Disinger, John F., Comp.

    Short descriptions of organizational structure and goals and descriptions of environmental education interests, activities, and priorities are presented for 32 nongovernmental organizations affiliated with the Alliance for Environmental Education. The organizations included are listed in the table of contents. The groups included represent a…

  17. Cancer and developmental exposure to endocrine disruptors.

    PubMed

    Birnbaum, Linda S; Fenton, Suzanne E

    2003-04-01

    Developing organisms have increased susceptibility to cancer if they are exposed to environmental toxicants during rapid growth and differentiation. Human studies have demonstrated clear increases in cancer after prenatal exposure to ionizing radiation, and there is suggestive evidence that brain tumors and leukemia are associated with parental exposures to chemicals. Animal experiments have demonstrated increased tumor formation induced by prenatal or neonatal exposure to a variety of chemicals, including direct-acting carcinogens and drugs. Recently, natural estrogens have been classified as known human carcinogens. Prenatal exposure to natural and synthetic estrogens is associated with increases in breast and vaginal tumors in humans as well as uterine tumors in animals. Synthetic halogenated chemicals increase liver tumors after early life-stage exposure. Recently, a prototypical endocrine-disrupting compound, 2,3,7,8-tetrachlorodibenzo-p-dioxin, has been shown to be a developmental toxicant of the mammary gland in rodents. Dioxin alters multiple endocrine systems, and its effects on the developing breast involve delayed proliferation and differentiation of the mammary gland, as well as an elongation of the window of sensitivity to potential carcinogens. Implications of these new findings suggest that causes of endocrine-related cancers or susceptibility to cancer may be a result of developmental exposures rather than exposures existing at or near the time of tumor detection.

  18. Systemic Effects of Non-Endocrine Tumours

    PubMed Central

    Sullivan, James D.; Rona, George

    1964-01-01

    Tumours of non-endocrine origin may exert deleterious effects by elaborating active principles which disturb body regulation. Systemic manifestations are fairly common with neoplasms of the lung, kidney, gastro-intestinal tract and thymus. The secretion of these tumours may have a known chemical structure (serotonin), may present hormone-like action (parathormone, antidiuretic hormone, insulinoid), or have well-defined biological properties (erythropoietin, gastrin-like principle). Tumours may stimulate endocrine glands by an unknown mechanism, producing disorders such as Cushing's syndrome, hypercalcemia, gynecomastia and hypoglycemia. Thymomas may be associated with autoimmune diseases. Tumours may extensively utilize or excrete some metabolite (glucose) or electrolyte (Na or K). Awareness of the systemic effects of various neoplasms may lead to an early diagnosis and proper treatment of these manifestations. PMID:14204555

  19. Endocrine disrupting chemicals and endometriosis.

    PubMed

    Smarr, Melissa M; Kannan, Kurunthachalam; Buck Louis, Germaine M

    2016-09-15

    Endometriosis is an estrogen dependent gynecologic disease with lasting implications for many women's fertility, somatic health, and overall quality of life. Growing evidence suggests that endocrine disrupting chemicals (EDCs) may be etiologically involved in the development and severity of disease. We weigh the available human evidence focusing on EDCs and endometriosis, restricting to research that has individually quantified chemical concentrations for women, included a comparison group of unaffected women, and used multivariable analytic techniques. Evidence supporting an environmental etiology for endometriosis includes metals/trace elements, dioxins, and other persistent organic pollutants, as well as nonpersistent chemicals, such as benzophenones and phthalates. To address the equivocal findings for various EDCs, future research directions for filling data gaps include [1] use of integrated clinical and population sampling frameworks allowing for incorporation of new diagnostic modalities; [2] the collection of various biologic media, including target tissues for quantifying exposures; [3] study designs that offer various comparison groups to assess potentially shared etiologies with other gynecologic disorders; and [4] novel laboratory and statistical approaches that fully explore all measured EDCs for the assessment of mixtures and low dose effects and the use of directed acyclic graphs and supporting causal analysis for empirically delineating relationships between EDCs and endometriosis. PMID:27424048

  20. Endocrine dysfunction in patients of leprosy

    PubMed Central

    Singh, Rohit Kumar; Bhasin, Rohit; Bisht, Y. S.; Kumar, K. V. S. Hari

    2015-01-01

    Background: Leprosy is a chronic granulomatous disease and affects many internal organs in addition to the skin and peripheral nerves. Endocrine dysfunction is often silent and is often missed in patients of leprosy leading to significant morbidity. We studied the presence of occult endocrine disorders in leprosy patients and compared the same with disease parameters. Materials and Methods: We evaluated 40 patients of leprosy (aged 18–70 years, any duration) in this cross-sectional, observational study. All subjects were assessed for pituitary, thyroid, adrenal, gonadal function, and dynamic testing was done when deemed necessary. The participants were divided into two groups: Group 1 (Leprosy, n = 40) and Group 2 (Controls, n = 20) and the data were analyzed with appropriate statistical tests. Results: The study participants (35 males, 5 females) had a mean age of 36.4 ± 11.3 years, and duration of the disease was 2.5 ± 5.5 years. Eleven out of 40 patients showed results consistent with an endocrine disorder, including subclinical hypothyroidism (n = 4), sick euthyroid syndrome (n = 3), growth hormone (GH) deficiency (n = 2), primary hypogonadism (n = 2) and secondary hypogonadism in one patient. One patient had partial hypopituitarism (GH deficiency and secondary hypogonadism) and none of the controls showed any hormonal dysfunction. Testosterone levels showed inverse correlation with the number of skin patches (P = 0.0006). Conclusion: Occult endocrine dysfunction is seen in a quarter of patients with leprosy. Thyroid and gonadal axes abnormalities are common, and the severity is more in lepromatous forms of the disease. Further large studies are required to confirm the findings observed in our study. PMID:25932392

  1. REST represses a subset of the pancreatic endocrine differentiation program.

    PubMed

    Martin, David; Kim, Yung-Hae; Sever, Dror; Mao, Chai-An; Haefliger, Jacques-Antoine; Grapin-Botton, Anne

    2015-09-15

    To contribute to devise successful beta-cell differentiation strategies for the cure of Type 1 diabetes we sought to uncover barriers that restrict endocrine fate acquisition by studying the role of the transcriptional repressor REST in the developing pancreas. Rest expression is prevented in neurons and in endocrine cells, which is necessary for their normal function. During development, REST represses a subset of genes in the neuronal differentiation program and Rest is down-regulated as neurons differentiate. Here, we investigate the role of REST in the differentiation of pancreatic endocrine cells, which are molecularly close to neurons. We show that Rest is widely expressed in pancreas progenitors and that it is down-regulated in differentiated endocrine cells. Sustained expression of REST in Pdx1(+) progenitors impairs the differentiation of endocrine-committed Neurog3(+) progenitors, decreases beta and alpha cell mass by E18.5, and triggers diabetes in adulthood. Conditional inactivation of Rest in Pdx1(+) progenitors is not sufficient to trigger endocrine differentiation but up-regulates a subset of differentiation genes. Our results show that the transcriptional repressor REST is active in pancreas progenitors where it gates the activation of part of the beta cell differentiation program. PMID:26156633

  2. REST represses a subset of the pancreatic endocrine differentiation program

    PubMed Central

    Martin, David; Kim, Yung-Hae; Sever, Dror; Mao, Chai-An; Haefiiger, Jacques-Antoine; Grapin-Botton, Anne

    2016-01-01

    To contribute to devise successful beta-cell differentiation strategies for the cure of Type 1 diabetes we sought to uncover barriers that restrict endocrine fate acquisition by studying the role of the transcriptional repressor REST in the developing pancreas. Rest expression is prevented in neurons and in endocrine cells, which is necessary for their normal function. During development, REST represses a subset of genes in the neuronal differentiation program and Rest is down-regulated as neurons differentiate. Here, we investigate the role of REST in the differentiation of pancreatic endocrine cells, which are molecularly close to neurons. We show that Rest is widely expressed in pancreas progenitors and that it is down-regulated in differentiated endocrine cells. Sustained expression of REST in Pdx1+ progenitors impairs the differentiation of endocrine-committed Neurog3+ progenitors, decreases beta and alpha cell mass by E18.5, and triggers diabetes in adulthood. Conditional inactivation of Rest in Pdx1+ progenitors is not sufficient to trigger endocrine differentiation but up-regulates a subset of differentiation genes. Our results show that the transcriptional repressor REST is active in pancreas progenitors where it gates the activation of part of the beta cell differentiation program. PMID:26156633

  3. Prediction of the endocrine disruption profile of pesticides.

    PubMed

    Devillers, J; Bro, E; Millot, F

    2015-01-01

    Numerous manmade chemicals released into the environment can interfere with normal, hormonally regulated biological processes to adversely affect the development and reproductive functions of living species. Various in vivo and in vitro tests have been designed for detecting endocrine disruptors, but the number of chemicals to test is so high that to save time and money, (quantitative) structure-activity relationship ((Q)SAR) models are increasingly used as a surrogate for these laboratory assays. However, most of them focus only on a specific target (e.g. estrogenic or androgenic receptor) while, to be more efficient, endocrine disruption modelling should preferentially consider profiles of activities to better gauge this complex phenomenon. In this context, an attempt was made to evaluate the endocrine disruption profile of 220 structurally diverse pesticides using the Endocrine Disruptome simulation (EDS) tool, which simultaneously predicts the probability of binding of chemicals on 12 nuclear receptors. In a first step, the EDS web-based system was successfully applied to 16 pharmaceutical compounds known to target at least one of the studied receptors. About 13% of the studied pesticides were estimated to be potential disruptors of the endocrine system due to their high predicted affinity for at least one receptor. In contrast, about 55% of them were unlikely to be endocrine disruptors. The simulation results are discussed and some comments on the use of the EDS tool are made.

  4. REST represses a subset of the pancreatic endocrine differentiation program.

    PubMed

    Martin, David; Kim, Yung-Hae; Sever, Dror; Mao, Chai-An; Haefliger, Jacques-Antoine; Grapin-Botton, Anne

    2015-09-15

    To contribute to devise successful beta-cell differentiation strategies for the cure of Type 1 diabetes we sought to uncover barriers that restrict endocrine fate acquisition by studying the role of the transcriptional repressor REST in the developing pancreas. Rest expression is prevented in neurons and in endocrine cells, which is necessary for their normal function. During development, REST represses a subset of genes in the neuronal differentiation program and Rest is down-regulated as neurons differentiate. Here, we investigate the role of REST in the differentiation of pancreatic endocrine cells, which are molecularly close to neurons. We show that Rest is widely expressed in pancreas progenitors and that it is down-regulated in differentiated endocrine cells. Sustained expression of REST in Pdx1(+) progenitors impairs the differentiation of endocrine-committed Neurog3(+) progenitors, decreases beta and alpha cell mass by E18.5, and triggers diabetes in adulthood. Conditional inactivation of Rest in Pdx1(+) progenitors is not sufficient to trigger endocrine differentiation but up-regulates a subset of differentiation genes. Our results show that the transcriptional repressor REST is active in pancreas progenitors where it gates the activation of part of the beta cell differentiation program.

  5. Prediction of the endocrine disruption profile of pesticides.

    PubMed

    Devillers, J; Bro, E; Millot, F

    2015-01-01

    Numerous manmade chemicals released into the environment can interfere with normal, hormonally regulated biological processes to adversely affect the development and reproductive functions of living species. Various in vivo and in vitro tests have been designed for detecting endocrine disruptors, but the number of chemicals to test is so high that to save time and money, (quantitative) structure-activity relationship ((Q)SAR) models are increasingly used as a surrogate for these laboratory assays. However, most of them focus only on a specific target (e.g. estrogenic or androgenic receptor) while, to be more efficient, endocrine disruption modelling should preferentially consider profiles of activities to better gauge this complex phenomenon. In this context, an attempt was made to evaluate the endocrine disruption profile of 220 structurally diverse pesticides using the Endocrine Disruptome simulation (EDS) tool, which simultaneously predicts the probability of binding of chemicals on 12 nuclear receptors. In a first step, the EDS web-based system was successfully applied to 16 pharmaceutical compounds known to target at least one of the studied receptors. About 13% of the studied pesticides were estimated to be potential disruptors of the endocrine system due to their high predicted affinity for at least one receptor. In contrast, about 55% of them were unlikely to be endocrine disruptors. The simulation results are discussed and some comments on the use of the EDS tool are made. PMID:26548639

  6. Endocrine-Disrupting Chemicals: Associated Disorders and Mechanisms of Action

    PubMed Central

    De Coster, Sam; van Larebeke, Nicolas

    2012-01-01

    The incidence and/or prevalence of health problems associated with endocrine-disruption have increased. Many chemicals have endocrine-disrupting properties, including bisphenol A, some organochlorines, polybrominated flame retardants, perfluorinated substances, alkylphenols, phthalates, pesticides, polycyclic aromatic hydrocarbons, alkylphenols, solvents, and some household products including some cleaning products, air fresheners, hair dyes, cosmetics, and sunscreens. Even some metals were shown to have endocrine-disrupting properties. Many observations suggesting that endocrine disruptors do contribute to cancer, diabetes, obesity, the metabolic syndrome, and infertility are listed in this paper. An overview is presented of mechanisms contributing to endocrine disruption. Endocrine disruptors can act through classical nuclear receptors, but also through estrogen-related receptors, membrane-bound estrogen-receptors, and interaction with targets in the cytosol resulting in activation of the Src/Ras/Erk pathway or modulation of nitric oxide. In addition, changes in metabolism of endogenous hormones, cross-talk between genomic and nongenomic pathways, cross talk with estrogen receptors after binding on other receptors, interference with feedback regulation and neuroendocrine cells, changes in DNA methylation or histone modifications, and genomic instability by interference with the spindle figure can play a role. Also it was found that effects of receptor activation can differ in function of the ligand. PMID:22991565

  7. Photocatalytic activity of ZnO doped with Ag on the degradation of endocrine disrupting under UV irradiation and the investigation of its antibacterial activity

    NASA Astrophysics Data System (ADS)

    Bechambi, Olfa; Chalbi, Manel; Najjar, Wahiba; Sayadi, Sami

    2015-08-01

    Ag-doped ZnO photocatalysts with different Ag molar content (0.0, 0.5, 1.0, 2.0 and 4.0%) were prepared via hydrothermal method. The X-ray diffraction (XRD), Nitrogen physisorption at 77 K, Fourier transformed infrared spectroscopy (FTIR), UV--Visible spectroscopy, Photoluminescence spectra (PL) and Raman spectroscopy were used to characterize the structural, textural and optical properties of the samples. The results showed that Ag-doping does not change the average crystallite size with the Ag low content (≤1.0%) but slightly decreases with Ag high content (>1.0%). The specific surface area (SBET) increases with the increase of the Ag content. The band gap values of ZnO are decreased with the increase of the Ag doping level. The results of the photocatalytic degradation of bisphenol A (BPA) and nonylphenol (NP) in aqueous solutions under UV irradiation and in the presence of hydrogen peroxide (H2O2) showed that silver ions doping greatly improved the photocatalytic efficiency of ZnO. The TOC conversion BPA and NP are 72.1% and 81.08% respectively obtained using 1% Ag-doped ZnO. The enhancement of photocatalytic activity is ascribed to the fact that the modification of ZnO with an appropriate amount of Ag can increase the separation efficiency of the photogenerated electrons-holes in ZnO. The antibacterial activity of the catalysts which uses Escherichia coli as a model for Gram-negative bacteria confirmed that Ag-doped ZnO possessed more antibacterial activity than the pure ZnO.

  8. Potential enzyme activities in cryoturbated organic matter of arctic soils

    NASA Astrophysics Data System (ADS)

    Schnecker, J.; Wild, B.; Rusalimova, O.; Mikutta, R.; Guggenberger, G.; Richter, A.

    2012-12-01

    An estimated 581 Gt organic carbon is stored in arctic soils that are affected by cryoturbtion, more than in today's atmosphere (450 Gt). The high amount of organic carbon is, amongst other factors, due to topsoil organic matter (OM) that has been subducted by freeze-thaw processes. This cryoturbated OM is usually hundreds to thousands of years old, while the chemical composition remains largely unaltered. It has therefore been suggested, that the retarded decomposition rates cannot be explained by unfavourable abiotic conditions in deeper soil layers alone. Since decomposition of soil organic material is dependent on extracellular enzymes, we measured potential and actual extracellular enzyme activities in organic topsoil, mineral subsoil and cryoturbated material from three different tundra sites, in Zackenberg (Greenland) and Cherskii (North-East Siberia). In addition we analysed the microbial community structure by PLFAs. Hydrolytic enzyme activities, calculated on a per gram dry mass basis, were higher in organic topsoil horizons than in cryoturbated horizons, which in turn were higher than in mineral horizons. When calculated on per gram carbon basis, the activity of the carbon acquiring enzyme exoglucanase was not significantly different between cryoturbated and topsoil organic horizons in any of the three sites. Oxidative enzymes, i.e. phenoloxidase and peroxidase, responsible for degradation of complex organic substances, showed higher activities in topsoil organic and cryoturbated horizons than in mineral horizons, when calculated per gram dry mass. Specific activities (per g C) however were highest in mineral horizons. We also measured actual cellulase activities (by inhibiting microbial uptake of products and without substrate addition): calculated per g C, the activities were up to ten times as high in organic topsoil compared to cryoturbated and mineral horizons, the latter not being significantly different. The total amount of PLFAs, as a proxy for

  9. [Endocrine effects of antiepileptic drugs].

    PubMed

    Leśkiewicz, Monika; Budziszewska, Bogusława; Lasoń, Władysław

    2008-01-01

    Both seizures and antiepileptic drugs may induce disturbances in hormonal system. Regarding endocrine effects of anticonvulsants, an interaction of these drugs with gonadal, thyroid, and adrenal axis deserves attention. Since majority of antiepileptic drugs block voltage dependent sodium and calcium channels, enhance GABAergic transmission and/or antagonize glutamate receptors, one may expect that similar neurochemical mechanisms are engaged in the interaction of these drugs with synthesis of hypothalamic neurohormones such as gonadotropin-releasing hormone (GnRH), thyrotropin-releasing hormone (TRH), corticotropin-releasing hormone (CRH) and growth hormone releasing hormone (GHRH). Moreover some antiepileptic drugs may affect hormone metabolism via inhibiting or stimulating cytochrome P-450 iso-enzymes. An influence of antiepileptic drugs on hypothalamic-pituitary-gonadal axis appears to be sex-dependent. In males, valproate decreased follicle-stimulating hormone (FSH) and luteinizing hormone (LH) but elevated dehydroepiandrosterone sulfate (DHEAS) concentrations. Carbamazepine decreased testosterone/sex-hormone binding globulin (SHBG) ratio, whereas its active metabolite--oxcarbazepine--had no effect on androgens. In females, valproate decreased FSH-stimulated estradiol release and enhanced testosterone level. On the other hand, carbamazepine decreased testosterone level but enhanced SHBG concentration. It has been reported that carbamazepine, oxcarbazepine or joined administration of carbamazepine and valproate decrease thyroxine (T4) level in patients with no effect on thyrotropin (TSH). While valproate itself has no effect on T4, phenytoin, phenobarbital and primidone, as metabolic enzyme inducers, can decrease the level of free and bound thyroxine. On the other hand, new antiepileptics such as levetiracetam, tiagabine, vigabatrine or lamotrigine had no effect on thyroid hormones. With respect to hormonal regulation of metabolic processes, valproate was

  10. Endocrine resistance in breast cancer: Current status and a perspective on the roles of miRNAs (Review)

    PubMed Central

    ZHOU, JICHUN; TENG, RONGYUE; WANG, QINCHUAN; XU, CHENPU; GUO, JUFENG; YUAN, CHAO; SHEN, JIANGUO; HU, WENXIAN; WANG, LINBO; XIE, SHUDUO

    2013-01-01

    Current endocrine therapies for females with estrogen receptor-positive breast cancer have facilitated substantial improvements in outcomes. The effectiveness of endocrine therapy is limited by either initial de novo resistance or acquired endocrine resistance. Multiple mechanisms responsible for endocrine resistance have been proposed, including deregulation of various components of the estrogen receptor (ER) pathway, alterations in cell cycle and cell survival signaling molecules, and the activation of escape pathways. Dysregulation of miRNA expression has been associated with experimental and clinical endocrine therapy resistance. miRNAs are pivotal to understanding the complex biological mechanism of endocrine resistance, and may serve as novel candidate predictive and prognostic surrogates and therapeutic targets. This review focuses on current progress concerning the roles of miRNAs in endocrine resistance, and discusses the challenges and opportunities for implementing miRNA-based assays and treatment for patients with endocrine-resistant breast cancer. PMID:24137320

  11. Cloud condensation nuclei activation of limited solubility organic aerosol

    NASA Astrophysics Data System (ADS)

    Huff Hartz, Kara E.; Tischuk, Joshua E.; Chan, Man Nin; Chan, Chak K.; Donahue, Neil M.; Pandis, Spyros N.

    The cloud condensation nuclei (CCN) activation of 19 organic species with water solubilities ( Csat) ranging from 10 -4 to 10 2 g solute 100 g -1 H 2O was measured. The organic particles were generated by nebulization of an aqueous or an alcohol solution. Use of alcohols as solvents enables the measurement of low solubility, non-volatile organic CCN activity and reduces the likelihood of residual water in the aerosol. The activation diameter of organic species with very low solubility in water ( Csat<0.3 g 100 g -1 H 2O) is in agreement with Köhler theory using the bulk solubility (limited solubility case) of the organic in water. Many species, including 2-acetylbenzoic acid, aspartic acid, azelaic acid, glutamic acid, homophthalic acid, phthalic acid, cis-pinonic acid, and salicylic acid are highly CCN active in spite of their low solubility (0.3 g 100 g -1 H 2O< Csat<1 g 100 g -1 H 2O), and activate almost as if completely water soluble. The CCN activity of most species is reduced, if the particles are produced using non-aqueous solvents. The existence of the particles in a metastable state at low RH can explain the observed enhancement in CCN activity beyond the levels suggested by their solubility.

  12. Developmental effects of endocrine-disrupting chemicals in wildlife and humans.

    PubMed Central

    Colborn, T; vom Saal, F S; Soto, A M

    1993-01-01

    Large numbers and large quantities of endocrine-disrupting chemicals have been released into the environment since World War II. Many of these chemicals can disturb development of the endocrine system and of the organs that respond to endocrine signals in organisms indirectly exposed during prenatal and/or early postnatal life; effects of exposure during development are permanent and irreversible. The risk to the developing organism can also stem from direct exposure of the offspring after birth or hatching. In addition, transgenerational exposure can result from the exposure of the mother to a chemical at any time throughout her life before producing offspring due to persistence of endocrine-disrupting chemicals in body fat, which is mobilized during egg laying or pregnancy and lactation. Mechanisms underlying the disruption of the development of vital systems, such as the endocrine, reproductive, and immune systems, are discussed with reference to wildlife, laboratory animals, and humans. PMID:8080506

  13. Wilson's disease: An endocrine revelation

    PubMed Central

    Kapoor, Nitin; Shetty, Sahana; Thomas, Nihal; Paul, Thomas Vizhalil

    2014-01-01

    Wilson's disease is an inherited disorder of copper metabolism. The affected patients, who otherwise have a near normal life span, may often suffer from some potentially treatable and under recognized endocrine disorders that may hinder their quality of life. We explored previously published literature on the various endocrine aspects of this disease with their probable underlying mechanisms, highlighting the universal need of research in this area. PMID:25364683

  14. Wilson's disease: An endocrine revelation.

    PubMed

    Kapoor, Nitin; Shetty, Sahana; Thomas, Nihal; Paul, Thomas Vizhalil

    2014-11-01

    Wilson's disease is an inherited disorder of copper metabolism. The affected patients, who otherwise have a near normal life span, may often suffer from some potentially treatable and under recognized endocrine disorders that may hinder their quality of life. We explored previously published literature on the various endocrine aspects of this disease with their probable underlying mechanisms, highlighting the universal need of research in this area. PMID:25364683

  15. Ngn3+ endocrine progenitor cells control the fate and morphogenesis of pancreatic ductal epithelium

    PubMed Central

    Magenheim, Judith; Klein, Allon M.; Stanger, Ben Z.; Ashery-Padan, Ruth; Sosa-Pineda, Beatriz; Gu, Guoqiang; Dor, Yuval

    2013-01-01

    Summary During pancreas development, endocrine and exocrine cells arise from a common multipotent progenitor pool. How these cell fate decisions are coordinated with tissue morphogenesis is poorly understood. Here we have examined ductal morphology, endocrine progenitor cell fate and Notch signaling in Ngn3−/− mice, which do not produce islet cells. Ngn3 deficiency results in reduced branching and enlarged pancreatic duct-like structures, concomitant with Ngn3 promoter activation throughout the ductal epithelium and reduced Notch signaling. Conversely, forced generation of surplus endocrine progenitor cells causes reduced duct caliber and an excessive number of tip cells. Thus, endocrine progenitor cells normally provide a feedback signal to adjacent multipotent ductal progenitor cells that activates Notch signaling, inhibits further endocrine differentiation and promotes proper morphogenesis. These results uncover a novel layer of regulation coordinating pancreas morphogenesis and endocrine/exocrine differentiation, and suggest ways to enhance the yield of beta-cells from stem cells. PMID:21888903

  16. Active control of magnetoresistance of organic spin valves using ferroelectricity

    PubMed Central

    Sun, Dali; Fang, Mei; Xu, Xiaoshan; Jiang, Lu; Guo, Hangwen; Wang, Yanmei; Yang, Wenting; Yin, Lifeng; Snijders, Paul C.; Ward, T. Z.; Gai, Zheng; Zhang, X.-G.; Lee, Ho Nyung; Shen, Jian

    2014-01-01

    Organic spintronic devices have been appealing because of the long spin lifetime of the charge carriers in the organic materials and their low cost, flexibility and chemical diversity. In previous studies, the control of resistance of organic spin valves is generally achieved by the alignment of the magnetization directions of the two ferromagnetic electrodes, generating magnetoresistance. Here we employ a new knob to tune the resistance of organic spin valves by adding a thin ferroelectric interfacial layer between the ferromagnetic electrode and the organic spacer: the magnetoresistance of the spin valve depends strongly on the history of the bias voltage, which is correlated with the polarization of the ferroelectric layer; the magnetoresistance even changes sign when the electric polarization of the ferroelectric layer is reversed. These findings enable active control of resistance using both electric and magnetic fields, opening up possibility for multi-state organic spin valves. PMID:25008155

  17. Active control of magnetoresistance of organic spin valves using ferroelectricity.

    PubMed

    Sun, Dali; Fang, Mei; Xu, Xiaoshan; Jiang, Lu; Guo, Hangwen; Wang, Yanmei; Yang, Wenting; Yin, Lifeng; Snijders, Paul C; Ward, T Z; Gai, Zheng; Zhang, X-G; Lee, Ho Nyung; Shen, Jian

    2014-01-01

    Organic spintronic devices have been appealing because of the long spin lifetime of the charge carriers in the organic materials and their low cost, flexibility and chemical diversity. In previous studies, the control of resistance of organic spin valves is generally achieved by the alignment of the magnetization directions of the two ferromagnetic electrodes, generating magnetoresistance. Here we employ a new knob to tune the resistance of organic spin valves by adding a thin ferroelectric interfacial layer between the ferromagnetic electrode and the organic spacer: the magnetoresistance of the spin valve depends strongly on the history of the bias voltage, which is correlated with the polarization of the ferroelectric layer; the magnetoresistance even changes sign when the electric polarization of the ferroelectric layer is reversed. These findings enable active control of resistance using both electric and magnetic fields, opening up possibility for multi-state organic spin valves. PMID:25008155

  18. Active control of magnetoresistance of organic spin valves using ferroelectricity

    NASA Astrophysics Data System (ADS)

    Shen, Jian

    Organic spintronic devices have been appealing because of the long spin lifetime of the charge carriers in the organic materials and their low cost, flexibility and chemical diversity. In previous studies, the control of resistance of organic spin valves is generally achieved by the alignment of the magnetization directions of the two ferromagnetic electrodes, generating magnetoresistance. Here we employ a new knob to tune the resistance of organic spin valves by adding a thin ferroelectric interfacial layer between the ferromagnetic electrode and the organic spacer: the magnetoresistance of the spin valve depends strongly on the history of the bias voltage, which is correlated with the polarization of the ferroelectric layer; the magnetoresistance even changes sign when the electric polarization of the ferroelectric layer is reversed. These findings enable active control of resistance using both electric and magnetic fields, opening up possibility for multi-state organic spin valves.

  19. [Endocrine abnormalities in patients with chronic renal failure - part II].

    PubMed

    Krysiak, Robert; Kędzia, Agnieszka; Krupej-Kędzierska, Joanna; Kowalska, Beata; Okopień, Bogusław

    2015-05-01

    The kidneys play a crucial role in maintaining homeostasis of fluids and electrolytes, acid-base balance, and volume regulation. In subjects with chronic renal failure, particularly at its later stages, these adaptive responses are impaired and some of these alterations are of clinical relevance. The ways in which chronic renal failure affects function of endocrine organs include impaired secretion of kidney-derived hormones, altered peripheral hormone metabolism, disturbed binding to carrier proteins, accumulation of hormone inhibitors, as well as abnormal target organ responsiveness. Apart from secondary hyperparathyroidism, thyroid dysfunction and impaired growth, reviewed in our previous study, endocrine disturbances that most frequently affect this group of patients include: abnormal functioning of the hypothalamic-pituitary-adrenal and hypothalamicpituitary- gonadal axes, bone loss and gynecomastia. The clinical picture and laboratory findings of these endocrine disturbances depend on the treatment strategy.

  20. Recent Advances on Endocrine Disrupting Effects of UV Filters.

    PubMed

    Wang, Jiaying; Pan, Liumeng; Wu, Shenggan; Lu, Liping; Xu, Yiwen; Zhu, Yanye; Guo, Ming; Zhuang, Shulin

    2016-01-01

    Ultraviolet (UV) filters are used widely in cosmetics, plastics, adhesives and other industrial products to protect human skin or products against direct exposure to deleterious UV radiation. With growing usage and mis-disposition of UV filters, they currently represent a new class of contaminants of emerging concern with increasingly reported adverse effects to humans and other organisms. Exposure to UV filters induce various endocrine disrupting effects, as revealed by increasing number of toxicological studies performed in recent years. It is necessary to compile a systematic review on the current research status on endocrine disrupting effects of UV filters toward different organisms. We therefore summarized the recent advances on the evaluation of the potential endocrine disruptors and the mechanism of toxicity for many kinds of UV filters such as benzophenones, camphor derivatives and cinnamate derivatives. PMID:27527194

  1. Recent Advances on Endocrine Disrupting Effects of UV Filters

    PubMed Central

    Wang, Jiaying; Pan, Liumeng; Wu, Shenggan; Lu, Liping; Xu, Yiwen; Zhu, Yanye; Guo, Ming; Zhuang, Shulin

    2016-01-01

    Ultraviolet (UV) filters are used widely in cosmetics, plastics, adhesives and other industrial products to protect human skin or products against direct exposure to deleterious UV radiation. With growing usage and mis-disposition of UV filters, they currently represent a new class of contaminants of emerging concern with increasingly reported adverse effects to humans and other organisms. Exposure to UV filters induce various endocrine disrupting effects, as revealed by increasing number of toxicological studies performed in recent years. It is necessary to compile a systematic review on the current research status on endocrine disrupting effects of UV filters toward different organisms. We therefore summarized the recent advances on the evaluation of the potential endocrine disruptors and the mechanism of toxicity for many kinds of UV filters such as benzophenones, camphor derivatives and cinnamate derivatives. PMID:27527194

  2. Recent Advances on Endocrine Disrupting Effects of UV Filters.

    PubMed

    Wang, Jiaying; Pan, Liumeng; Wu, Shenggan; Lu, Liping; Xu, Yiwen; Zhu, Yanye; Guo, Ming; Zhuang, Shulin

    2016-08-03

    Ultraviolet (UV) filters are used widely in cosmetics, plastics, adhesives and other industrial products to protect human skin or products against direct exposure to deleterious UV radiation. With growing usage and mis-disposition of UV filters, they currently represent a new class of contaminants of emerging concern with increasingly reported adverse effects to humans and other organisms. Exposure to UV filters induce various endocrine disrupting effects, as revealed by increasing number of toxicological studies performed in recent years. It is necessary to compile a systematic review on the current research status on endocrine disrupting effects of UV filters toward different organisms. We therefore summarized the recent advances on the evaluation of the potential endocrine disruptors and the mechanism of toxicity for many kinds of UV filters such as benzophenones, camphor derivatives and cinnamate derivatives.

  3. Endocrine Function In Naturally Long-Living Small Mammals

    PubMed Central

    Buffenstein, Rochelle; Pinto, Mario

    2015-01-01

    The complex, highly integrative endocrine system regulates all aspects of somatic maintenance and reproduction and has been widely implicated as an important determinant of longevity in short-lived traditional model organisms of aging research. Genetic or experimental manipulation of hormone profiles in mice has been proven to definitively alter longevity. These hormonally induced lifespan extension mechanisms may not necessarily be relevant to humans and other long-lived organisms that naturally show successful slow aging. Long-lived species may have evolved novel anti-aging defenses germane to naturally retarding the aging process. Here we examine the available endocrine data associated with the vitamin D, insulin, grlucocorticoid and thyroid endocrine systems of naturally long-living small mammals. Generally, long-living rodents and bats maintain tightly regulated lower basal levels of these key pleiotropic hormones than shorter-lived rodents. Similarities with genetically manipulated suggest that evolutionarily wellconserved hormonal mechanisms are integrally involved in lifespan determination. PMID:18674586

  4. Hormones in the city: endocrine ecology of urban birds.

    PubMed

    Bonier, Frances

    2012-05-01

    Urbanization dramatically changes the landscape, presenting organisms with novel challenges and often leading to reduced species diversity. Urban ecologists have documented numerous biotic and abiotic consequences of urbanization, such as altered climate, species interactions, and community composition, but we lack an understanding of the mechanisms underlying organisms' responses to urbanization. Here, I review findings from the nascent field of study of the endocrine ecology of urban birds. Thus far, no clear or consistent patterns have been revealed, but we do have evidence that urban habitat can shape endocrine traits, and that those traits might contribute to adaptation to the urban environment. I suggest strong approaches for future work addressing exciting questions about the role of endocrine traits in mediating responses to urbanization within species across the globe.

  5. HOXB7 is an ERα cofactor in the activation of HER2 and multiple ER target genes leading to endocrine resistance

    PubMed Central

    Jin, Kideok; Park, Sunju; Teo, Wei Wen; Korangath, Preethi; Cho, Sean Soonweng; Yoshida, Takahiro; Győrffy, Balázs; Goswami, Chirayu Pankaj; Nakshatri, Harikrishna; Cruz, Leigh-Ann; Zhou, Weiqiang; Ji, Hongkai; Su, Ying; Ekram, Muhammad; Wu, Zhengsheng; Zhu, Tao; Polyak, Kornelia; Sukumar, Saraswati

    2015-01-01

    Why breast cancers become resistant to tamoxifen despite continued expression of the estrogen receptor alpha (ERα) and what factors are responsible for high HER2 expression in these tumors remains an enigma. HOXB7 ChIP analysis followed by validation showed that HOXB7 physically interacts with ERα, and that the HOXB7-ERα complex enhances transcription of many ERα target genes including HER2. Investigating strategies for controlling HOXB7, our studies revealed that MYC, stabilized via phosphorylation mediated by EGFR-HER2 signaling, inhibits transcription of miRNA-196a, a HOXB7 repressor. This leads to increased expression of HOXB7, ER-target genes and HER2. Repressing MYC using small molecule inhibitors reverses these events, and causes regression of breast cancer xenografts. The MYC-HOXB7-HER2 signaling pathway is eminently targetable in endocrine-resistant breast cancer. PMID:26180042

  6. Activism or "Slacktivism?": Digital Media and Organizing for Social Change

    ERIC Educational Resources Information Center

    Glenn, Cerise L.

    2015-01-01

    The influence of social media and technological developments has changed how groups and organizations advocating for social change generate awareness and participation in their causes. In this single class activity students will (a) analyze notions of activism and "slacktivism" from scholarly and popular sources to apply these concepts…

  7. Organic Mastery: An Activity for the Undergraduate Classroom

    ERIC Educational Resources Information Center

    Mosher, Michael D.; Mosher, Melvyn W.; Garoutte, Michael P.

    2012-01-01

    A group activity for use in the classroom or recitation section of an organic chemistry course is described. This activity, a board game using trivia and concepts from the course material, can be used periodically throughout the semester to introduce or reinforce content knowledge. Alternate versions can be easily constructed for other courses.…

  8. Non-invasive endocrine monitoring of ovarian and adrenal activity in chinchilla (Chinchilla lanigera) females during pregnancy, parturition and early post-partum period.

    PubMed

    Mastromonaco, Gabriela F; Cantarelli, Verónica I; Galeano, María G; Bourguignon, Nadia S; Gilman, Christine; Ponzio, Marina F

    2015-03-01

    The chinchilla is a rodent that bears one of the finest and most valuable pelts in the world. The wild counterpart is, however, almost extinct because of a drastic past and ongoing population decline. The present work was developed to increase our knowledge of the reproductive physiology of pregnancy and post-partum estrus in the chinchilla, characterizing the endocrine patterns of urinary progesterone, estradiol, LH and cortisol metabolites throughout gestation and post-partum estrus and estimating the ovulation timing at post-partum estrus. Longitudinal urine samples were collected once per week throughout pregnancy and analyzed for creatinine, cortisol, LH, estrogen and progesterone metabolite concentrations. To indirectly determine the ovulation timing at post-partum estrus, a second experiment was performed using pregnant females subjected to a post-partum in vivo fertilization scheme. Urinary progestagen metabolites increased above baseline levels in early pregnancy between weeks-8 and -11 respectively to parturition, and slightly declined at parturition time. Urinary estrogens showed rising levels throughout mid- and late pregnancy (weeks-9 to -6 and a further increase at week-5 to parturition) and decreased in a stepwise manner after parturition, returning to baseline levels two weeks thereafter. Cortisol metabolite levels were relatively constant throughout pregnancy with a tendency for higher levels in the last third of gestation and after the pups' birth. Parturition was associated with dramatic reductions in urinary concentrations of sex steroids (especially progestagens). Observations in breeding farms indicated that the females that resulted in a second pregnancy after mating, did so on the second day after parturition. These data were in agreement with an LH peak detected 24h after parturition. Urinary steroid hormone patterns of estrogen and progestagen metabolites provided valuable information on endocrine events during pregnancy and after

  9. Non-invasive endocrine monitoring of ovarian and adrenal activity in chinchilla (Chinchilla lanigera) females during pregnancy, parturition and early post-partum period.

    PubMed

    Mastromonaco, Gabriela F; Cantarelli, Verónica I; Galeano, María G; Bourguignon, Nadia S; Gilman, Christine; Ponzio, Marina F

    2015-03-01

    The chinchilla is a rodent that bears one of the finest and most valuable pelts in the world. The wild counterpart is, however, almost extinct because of a drastic past and ongoing population decline. The present work was developed to increase our knowledge of the reproductive physiology of pregnancy and post-partum estrus in the chinchilla, characterizing the endocrine patterns of urinary progesterone, estradiol, LH and cortisol metabolites throughout gestation and post-partum estrus and estimating the ovulation timing at post-partum estrus. Longitudinal urine samples were collected once per week throughout pregnancy and analyzed for creatinine, cortisol, LH, estrogen and progesterone metabolite concentrations. To indirectly determine the ovulation timing at post-partum estrus, a second experiment was performed using pregnant females subjected to a post-partum in vivo fertilization scheme. Urinary progestagen metabolites increased above baseline levels in early pregnancy between weeks-8 and -11 respectively to parturition, and slightly declined at parturition time. Urinary estrogens showed rising levels throughout mid- and late pregnancy (weeks-9 to -6 and a further increase at week-5 to parturition) and decreased in a stepwise manner after parturition, returning to baseline levels two weeks thereafter. Cortisol metabolite levels were relatively constant throughout pregnancy with a tendency for higher levels in the last third of gestation and after the pups' birth. Parturition was associated with dramatic reductions in urinary concentrations of sex steroids (especially progestagens). Observations in breeding farms indicated that the females that resulted in a second pregnancy after mating, did so on the second day after parturition. These data were in agreement with an LH peak detected 24h after parturition. Urinary steroid hormone patterns of estrogen and progestagen metabolites provided valuable information on endocrine events during pregnancy and after

  10. Urban Endocrine Disruptors Targeting Breast Cancer Proteins.

    PubMed

    Montes-Grajales, Diana; Bernardes, Gonçalo J L; Olivero-Verbel, Jesus

    2016-02-15

    Humans are exposed to a huge amount of environmental pollutants called endocrine disrupting chemicals (EDCs). These molecules interfere with the homeostasis of the body, usually through mimicking natural hormones leading to activation or blocking of their receptors. Many of these compounds have been associated with a broad range of diseases including the development or increased susceptibility to breast cancer, the most prevalent cancer in women worldwide, according to the World Health Organization. Thus, this article presents a virtual high-throughput screening (vHTS) to evaluate the affinity of proteins related to breast cancer, such as ESR1, ERBB2, PGR, BCRA1, and SHBG, among others, with EDCs from urban sources. A blind docking strategy was employed to screen each protein-ligand pair in triplicate in AutoDock Vina 2.0, using the computed binding affinities as ranking criteria. The three-dimensional structures were previously obtained from EDCs DataBank and Protein Data Bank, prepared and optimized by SYBYL X-2.0. Some of the chemicals that exhibited the best affinity scores for breast cancer proteins in each category were 1,3,7,8-tetrachlorodibenzo-p-dioxin, bisphenol A derivatives, perfluorooctanesulfonic acid, and benzo(a)pyrene, for catalase, several proteins, sex hormone-binding globulin, and cytochrome P450 1A2, respectively. An experimental validation of this approach was performed with a complex that gave a moderate binding affinity in silico, the sex hormone binding globulin (SHBG), and bisphenol A (BPA) complex. The protein was obtained using DNA recombinant technology and the physical interaction with BPA assessed through spectroscopic techniques. BPA binds on the recombinant SHBG, and this results in an increase of its α helix content. In short, this work shows the potential of several EDCs to bind breast cancer associated proteins as a tool to prioritize compounds to perform in vitro analysis to benefit the regulation or exposure prevention by the

  11. Enzyme activities by indicator of quality in organic soil

    NASA Astrophysics Data System (ADS)

    Raigon Jiménez, Mo; Fita, Ana Delores; Rodriguez Burruezo, Adrián

    2016-04-01

    The analytical determination of biochemical parameters, as soil enzyme activities and those related to the microbial biomass is growing importance by biological indicator in soil science studies. The metabolic activity in soil is responsible of important processes such as mineralization and humification of organic matter. These biological reactions will affect other key processes involved with elements like carbon, nitrogen and phosphorus , and all transformations related in soil microbial biomass. The determination of biochemical parameters is useful in studies carried out on organic soil where microbial processes that are key to their conservation can be analyzed through parameters of the metabolic activity of these soils. The main objective of this work is to apply analytical methodologies of enzyme activities in soil collections of different physicochemical characteristics. There have been selective sampling of natural soils, organic farming soils, conventional farming soils and urban soils. The soils have been properly identified conserved at 4 ° C until analysis. The enzyme activities determinations have been: catalase, urease, cellulase, dehydrogenase and alkaline phosphatase, which bring together a representative group of biological transformations that occur in the soil environment. The results indicate that for natural and agronomic soil collections, the values of the enzymatic activities are within the ranges established for forestry and agricultural soils. Organic soils are generally higher level of enzymatic, regardless activity of the enzyme involved. Soil near an urban area, levels of activities have been significantly reduced. The vegetation cover applied to organic soils, results in greater enzymatic activity. So the quality of these soils, defined as the ability to maintain their biological productivity is increased with the use of cover crops, whether or spontaneous species. The practice of cover based on legumes could be used as an ideal choice

  12. α-Galactosidase A expressed in the salivary glands partially corrects organ biochemical deficits in the fabry mouse through endocrine trafficking.

    PubMed

    Passineau, Michael J; Fahrenholz, Timothy; Machen, Laurie; Zourelias, Lee; Nega, Katherine; Paul, Rachel; MacDougall, Mary J; Mamaeva, Olga; Steet, Richard; Barnes, Jarrod; Kingston, H M; Benza, Raymond L

    2011-03-01

    Fabry disease is caused by an X-linked deficiency of the lysosomal enzyme α-galactosidase A (GLA) and has been treated successfully with enzyme replacement therapy (ERT). Gene therapy has been proposed as an alternative to ERT due to the presumed advantages of continuous, endogenous production of the therapeutic enzyme. GLA production in the liver and its therapeutic efficacy in the Fabry mouse have been demonstrated previously with various viral vector systems. In consideration of the potential advantages of using the salivary glands as endogenous GLA biosynthesis sites, we explored the feasibility of this approach in the Fabry mouse. GLA -/0 or -/- mice received an adenoviral vector (2 × 10(10) or 1 × 10(9) viral particles) expressing GLA to the right submandibular gland via oral cannulation of the submandibular duct. Four days later, animals were sacrificed; saliva, plasma, kidney, liver, and brain were collected and assayed using ELISA, Western blot, and a GLA enzymatic activity assay using both traditional fluorescence methods and isotope dilution mass spectrometry by following the U.S. EPA Method 6800. GLA activity was significantly elevated in the serum and liver of both treatment groups, and improvement in the kidney was marginally significant (P < 0.069) in the high-dose group. Notably, we found that liver and salivary gland produce different glycoforms of the GLA transgene. Only small numbers of adenoviral genomes were observed in the livers of treated animals, but in four of 14 in the high-dose groups, liver levels of adenovirus exceeded 20 copies/μg, indicating that the sequestration in the salivary gland was imperfect at high doses. Taken together, these results indicate that the salivary gland-based gene therapy for Fabry disease is promising, and further studies with advanced viral vector gene delivery systems (e.g., adeno-associated virus) for long-term treatment appear to be warranted. PMID:20858137

  13. Health Disparities in Endocrine Disorders: Biological, Clinical, and Nonclinical Factors—An Endocrine Society Scientific Statement

    PubMed Central

    Brown, Arleen; Cauley, Jane A.; Chin, Marshall H.; Gary-Webb, Tiffany L.; Kim, Catherine; Sosa, Julie Ann; Sumner, Anne E.; Anton, Blair

    2012-01-01

    Objective: The aim was to provide a scholarly review of the published literature on biological, clinical, and nonclinical contributors to race/ethnic and sex disparities in endocrine disorders and to identify current gaps in knowledge as a focus for future research needs. Participants in Development of Scientific Statement: The Endocrine Society's Scientific Statement Task Force (SSTF) selected the leader of the statement development group (S.H.G.). She selected an eight-member writing group with expertise in endocrinology and health disparities, which was approved by the Society. All discussions regarding the scientific statement content occurred via teleconference or written correspondence. No funding was provided to any expert or peer reviewer, and all participants volunteered their time to prepare this Scientific Statement. Evidence: The primary sources of data on global disease prevalence are from the World Health Organization. A comprehensive literature search of PubMed identified U.S. population-based studies. Search strategies combining Medical Subject Headings terms and keyword terms and phrases defined two concepts: 1) racial, ethnic, and sex differences including specific populations; and 2) the specific endocrine disorder or condition. The search identified systematic reviews, meta-analyses, large cohort and population-based studies, and original studies focusing on the prevalence and determinants of disparities in endocrine disorders. Consensus Process: The writing group focused on population differences in the highly prevalent endocrine diseases of type 2 diabetes mellitus and related conditions (prediabetes and diabetic complications), gestational diabetes, metabolic syndrome with a focus on obesity and dyslipidemia, thyroid disorders, osteoporosis, and vitamin D deficiency. Authors reviewed and synthesized evidence in their areas of expertise. The final statement incorporated responses to several levels of review: 1) comments of the SSTF and the

  14. Telomerase and the endocrine system.

    PubMed

    Pacini, Furio; Cantara, Silvia; Capezzone, Marco; Marchisotta, Stefania

    2011-03-29

    Telomeres are nucleoprotein complexes located at the ends of chromosomes that have a critical role in the maintenance of chromosomal integrity. This involvement is based on complex secondary and tertiary structures that rely on DNA-DNA, DNA-protein and protein-protein interactions. De novo synthesis and maintenance of telomere repeats is controlled by telomerase, a specialized complex that consists of a telomerase RNA component and a protein component--telomerase reverse transcriptase. When telomerase is silent (its default state in differentiated somatic cells), chromosomes shorten with every cell division, thus limiting the lifespan of the cells (the process of senescence) and preventing unlimited cell proliferation, which might eventually lead to the development of cancer. During this process, occasionally, a cell can activate telomerase, which stabilizes short telomeres and enables immortalization-a process essential for malignant transformation. Thus, although telomere erosion is a barrier to malignant progression, paradoxically, in certain circumstances it might also trigger tumorigenesis. A number of studies have demonstrated unequivocally that reactivation of telomerase in the presence of short telomeres is one of the most common features of human cancers, including those of the endocrine system.

  15. Endocrine disrupters: a human risk?

    PubMed

    Waring, R H; Harris, R M

    2005-12-01

    Endocrine disrupters (EDs) alter normal hormonal regulation and may be naturally occurring or environmental contaminants. Classically, EDs act genomically, with agonistic or antagonistic effects on steroid receptors and may alter reproductive function and/or cause feminisation by binding to oestrogen or androgen receptors; their binding to the thyroid receptor may dysregulate the neuroendocrine system. Recently, it has been shown that EDs can also act by non-genomic mechanisms, altering steroid synthesis (inhibition of cytochrome P450 isoforms) or steroid metabolism. The alkylphenol and phthalate plasticisers inhibit the inactivation of oestrogens by sulphation (via SULT 1A1 and 1E1 isoforms) and so cause a rise in levels of the free active endogenous oestrogens. A range of ED effects have been shown in mammals, fish, birds, reptiles, amphibia and aquatic invertebrates but it is not yet clear whether these processes also occur in human beings. It is evident that EDs, as well as altering reproduction, can cause changes in neurosteroid levels and so have the potential to affect immune function, behaviour and memory. This may be of long-term concern since traces of EDs such as plasticisers, brominated fire retardants, sunscreen agents and cosmetic ingredients are widely distributed in the environment and in human biofluids. PMID:16271281

  16. Endocrine remodelling of the adult intestine sustains reproduction in Drosophila.

    PubMed

    Reiff, Tobias; Jacobson, Jake; Cognigni, Paola; Antonello, Zeus; Ballesta, Esther; Tan, Kah Junn; Yew, Joanne Y; Dominguez, Maria; Miguel-Aliaga, Irene

    2015-01-01

    The production of offspring is energetically costly and relies on incompletely understood mechanisms that generate a positive energy balance. In mothers of many species, changes in key energy-associated internal organs are common yet poorly characterised functionally and mechanistically. In this study, we show that, in adult Drosophila females, the midgut is dramatically remodelled to enhance reproductive output. In contrast to extant models, organ remodelling does not occur in response to increased nutrient intake and/or offspring demands, but rather precedes them. With spatially and temporally directed manipulations, we identify juvenile hormone (JH) as an anticipatory endocrine signal released after mating. Acting through intestinal bHLH-PAS domain proteins Methoprene-tolerant (Met) and Germ cell-expressed (Gce), JH signals directly to intestinal progenitors to yield a larger organ, and adjusts gene expression and sterol regulatory element-binding protein (SREBP) activity in enterocytes to support increased lipid metabolism. Our findings identify a metabolically significant paradigm of adult somatic organ remodelling linking hormonal signals, epithelial plasticity, and reproductive output.

  17. Endocrine remodelling of the adult intestine sustains reproduction in Drosophila

    PubMed Central

    Reiff, Tobias; Jacobson, Jake; Cognigni, Paola; Antonello, Zeus; Ballesta, Esther; Tan, Kah Junn; Yew, Joanne Y; Dominguez, Maria; Miguel-Aliaga, Irene

    2015-01-01

    The production of offspring is energetically costly and relies on incompletely understood mechanisms that generate a positive energy balance. In mothers of many species, changes in key energy-associated internal organs are common yet poorly characterised functionally and mechanistically. In this study, we show that, in adult Drosophila females, the midgut is dramatically remodelled to enhance reproductive output. In contrast to extant models, organ remodelling does not occur in response to increased nutrient intake and/or offspring demands, but rather precedes them. With spatially and temporally directed manipulations, we identify juvenile hormone (JH) as an anticipatory endocrine signal released after mating. Acting through intestinal bHLH-PAS domain proteins Methoprene-tolerant (Met) and Germ cell-expressed (Gce), JH signals directly to intestinal progenitors to yield a larger organ, and adjusts gene expression and sterol regulatory element-binding protein (SREBP) activity in enterocytes to support increased lipid metabolism. Our findings identify a metabolically significant paradigm of adult somatic organ remodelling linking hormonal signals, epithelial plasticity, and reproductive output. DOI: http://dx.doi.org/10.7554/eLife.06930.001 PMID:26216039

  18. [Endocrine disease in adrenoleukodystrophy].

    PubMed

    Girard, S; Bruckert, E; Turpin, G

    2001-02-01

    X-linked adrenoleukodysrophy is the most frequent genetic disorder affecting central and peripheral nervous system myelin. One of the biochemical abnormalities is the accumulation of very long chain fatty acids (VLCFA) in tissues and body fluids subsequent to defective catabolism in the peroxysomes. The principal characteristic of the disease is an association between a neurological disorder and an endocrine disorder: primary adrenal insufficiency and testicular failure. Clinical manifestations are variable. There are two main forms, one affecting boys between the age of 5 and 10 years with severe rapidly fatal cerebral involvement, and the other affecting young adults between the age of 20 and 30 years with degeneration of the anterior and posterior long spinal cord tracts, similar to the disorders observed in multiple sclerosis. About 20% of the heterozygous women may develop a syndrome which resembles adrenomyeloneuropathy, rarely adrenal insufficiency. Adrenal insufficiency is present in 85% of the childhood cerebral forms and in about 70% of the adult forms. It may occur before, after or at the same time as the neurological disease but is not correlated with the severity of the neurological disorder. Careful screening is required to avoid missing subclinical forms. Adrenoleukodystrophy should be envisaged in young boys with primary adrenal insufficiency, accounting for about 30% of the cases of primary adrenal insufficiency in children under 3 years of age and about 13% of those in adults. Experience with dietary therapy (low-VLCFA diet and supplementation with unsaturated fatty acids such as glyceryl trioleate (GTO) and glyceryl trierucate (GTE), commonly called Lorenzo's oil) has not demonstrated any clinical improvement in the cerebral forms. Bone marrow transplantation is recommended for children who show early evidence of cerebral involvement. Gene therapy is a promising perspective. Lovastatin and 4-phenlbutyrate have recently been shown to normalize

  19. Drug Trafficking Organizations and Local Economic Activity in Mexico.

    PubMed

    González, Felipe

    2015-01-01

    Little is known about the relationship between illegal firms and local economic activity. In this paper I study changes in satellite night lights across Mexican municipalities after the arrival of large drug trafficking organizations in the period 2000-2010. After accounting for state trends and differences in political regimes, results indicate no significant change in night lights after the arrival of these illegal firms. Estimated coefficients are precise, robust, and similar across different drug trafficking organizations.

  20. Drug Trafficking Organizations and Local Economic Activity in Mexico.

    PubMed

    González, Felipe

    2015-01-01

    Little is known about the relationship between illegal firms and local economic activity. In this paper I study changes in satellite night lights across Mexican municipalities after the arrival of large drug trafficking organizations in the period 2000-2010. After accounting for state trends and differences in political regimes, results indicate no significant change in night lights after the arrival of these illegal firms. Estimated coefficients are precise, robust, and similar across different drug trafficking organizations. PMID:26348041

  1. Drug Trafficking Organizations and Local Economic Activity in Mexico

    PubMed Central

    González, Felipe

    2015-01-01

    Little is known about the relationship between illegal firms and local economic activity. In this paper I study changes in satellite night lights across Mexican municipalities after the arrival of large drug trafficking organizations in the period 2000–2010. After accounting for state trends and differences in political regimes, results indicate no significant change in night lights after the arrival of these illegal firms. Estimated coefficients are precise, robust, and similar across different drug trafficking organizations. PMID:26348041

  2. Effects of Common Pesticides on Prostaglandin D2 (PGD2) Inhibition in SC5 Mouse Sertoli Cells, Evidence of Binding at the COX-2 Active Site, and Implications for Endocrine Disruption

    PubMed Central

    Kugathas, Subramaniam; Audouze, Karine; Ermler, Sibylle; Orton, Frances; Rosivatz, Erika; Scholze, Martin; Kortenkamp, Andreas

    2015-01-01

    Background: There are concerns that diminished prostaglandin action in fetal life could increase the risk of congenital malformations. Many endocrine-disrupting chemicals have been found to suppress prostaglandin synthesis, but to our knowledge, pesticides have never been tested for these effects. Objectives: We assessed the ability of pesticides that are commonly used in the European Union to suppress prostaglandin D2 (PGD2) synthesis. Methods: Changes in PGD2 secretion in juvenile mouse Sertoli cells (SC5 cells) were measured using an ELISA. Coincubation with arachidonic acid (AA) was conducted to determine the site of action in the PGD2 synthetic pathway. Molecular modeling studies were performed to assess whether pesticides identified as PGD2-active could serve as ligands of the cyclooxygenase-2 (COX-2) binding pocket. Results: The pesticides boscalid, chlorpropham, cypermethrin, cyprodinil, fenhexamid, fludioxonil, imazalil (enilconazole), imidacloprid, iprodione, linuron, methiocarb, o-phenylphenol, pirimiphos-methyl, pyrimethanil, and tebuconazole suppressed PGD2 production. Strikingly, some of these substances—o-phenylphenol, cypermethrin, cyprodinil, linuron, and imazalil (enilconazole)—showed potencies (IC50) in the range between 175 and 1,500 nM, similar to those of analgesics intended to block COX enzymes. Supplementation with AA failed to reverse this effect, suggesting that the sites of action of these pesticides are COX enzymes. The molecular modeling studies revealed that the COX-2 binding pocket can accommodate most of the pesticides shown to suppress PGD2 synthesis. Some of these pesticides are also capable of antagonizing the androgen receptor. Conclusions: Chemicals with structural features more varied than previously thought can suppress PGD2 synthesis. Our findings signal a need for in vivo studies to establish the extent of endocrine-disrupting effects that might arise from simultaneous interference with PGD2 signaling and androgen action

  3. Tankyrase Activity in Organs and Tissues of Mice.

    PubMed

    Kuimov, A N; Zhozhikashvili, A S; Manskikh, V N; Platonova, L V; Dyuzheva, T G

    2016-03-01

    Tankyrase, one of the NAD+ ADP-ribosyltransferases, is a target for drugs developed for their anticancer and other pharmacological activities. We designed an assay for estimation of the inhibition or activation of the enzyme in preclinical studies. In mice, the highest specific activity of tankyrase was observed in thymus, spleen, pancreas, and bone marrow. In murine liver, tankyrase is active in ontogenesis and during reparative regeneration; however, the basal activity is hardly detectable in normal liver and most of other organs of adult animals. We suggest that tankyrase is a part of the tissue growth and repair machinery, while its age-dependent inhibition, when an organism stops growing, turns on phenoptosis. PMID:27262195

  4. The evolving role of physician organizations in quality related activities

    PubMed Central

    2014-01-01

    As the fields of quality assessment and improvement become integral parts of medical practice, the roles of National Medical Associations, and other physician organizations in these endeavors have undergone major changes in scope and intensity as well. The survey based report in this journal by Levi et al. suggests some major overall trends but also notes wide variation from country to country. In this commentary, we touch on some likely reasons for the variation seen in the focus of physician organization participation in quality activities, and offer some suggestions for why expanded involvement by physician organizations may be critical to quality efforts going forward. PMID:24959345

  5. Are Endocrine Disrupting Compounds a Health Risk in Drinking Water?

    PubMed Central

    Falconer, Ian R.

    2006-01-01

    There has been a great deal of international discussion on the nature and relevance of endocrine disrupting compounds in the environment. Changes in reproductive organs of fish and mollusks have been demonstrated in rivers downstream of sewage discharges in Europe and in North America, which have been attributed to estrogenic compounds in the effluent. The anatomical and physiological changes in the fauna are illustrated by feminization of male gonads. The compounds of greatest hormonal activity in sewage effluent are the natural estrogens 17β-estradiol, estrone, estriol and the synthetic estrogen ethinylestradiol. Androgens are also widely present in wastewaters. Investigations of anthropogenic chemical contaminants in freshwaters and wastewaters have shown a wide variety of organic compounds, many of which have low levels of estrogenic activity. In many highly populated countries the drinking water is sourced from the same rivers and lakes that are the recipients of sewage and industrial discharge. The River Thames which flows through London, England, has overall passed through drinking water and sewage discharge 5 times from source to mouth of the river. Under these types of circumstance, any accumulation of endocrine disrupting compounds from sewage or industry potentially affects the quality of drinking water. Neither basic wastewater treatment nor basic drinking water treatment will eliminate the estrogens, androgens or detergent breakdown products from water, due to the chemical stability of the structures. Hence a potential risk to health exists; however present data indicate that estrogenic contamination of drinking water is very unlikely to result in physiologically detectable effects in consumers. Pesticide, detergent and industrial contamination remain issues of concern. As a result of this concern, increased attention is being given to enhanced wastewater treatment in locations where the effluent is directly or indirectly in use for drinking water. In

  6. Are endocrine disrupting compounds a health risk in drinking water?

    PubMed

    Falconer, Ian R

    2006-06-01

    There has been a great deal of international discussion on the nature and relevance of endocrine disrupting compounds in the environment. Changes in reproductive organs of fish and mollusks have been demonstrated in rivers downstream of sewage discharges in Europe and in North America, which have been attributed to estrogenic compounds in the effluent. The anatomical and physiological changes in the fauna are illustrated by feminization of male gonads. The compounds of greatest hormonal activity in sewage effluent are the natural estrogens 17Beta-estradiol, estrone, estriol and the synthetic estrogen ethinylestradiol. Androgens are also widely present in wastewaters. Investigations of anthropogenic chemical contaminants in freshwaters and wastewaters have shown a wide variety of organic compounds, many of which have low levels of estrogenic activity. In many highly populated countries the drinking water is sourced from the same rivers and lakes that are the recipients of sewage and industrial discharge. The River Thames which flows through London, England, has overall passed through drinking water and sewage discharge 5 times from source to mouth of the river. Under these types of circumstance, any accumulation of endocrine disrupting compounds from sewage or industry potentially affects the quality of drinking water. Neither basic wastewater treatment nor basic drinking water treatment will eliminate the estrogens, androgens or detergent breakdown products from water, due to the chemical stability of the structures. Hence a potential risk to health exists; however present data indicate that estrogenic contamination of drinking water is very unlikely to result in physiologically detectable effects in consumers. Pesticide, detergent and industrial contamination remain issues of concern. As a result of this concern, increased attention is being given to enhanced wastewater treatment in locations where the effluent is directly or indirectly in use for drinking water

  7. Evaluation of Water Treatment Methods for Endocrine Disrupting Compounds

    NASA Astrophysics Data System (ADS)

    Thomas, S. M.; Murray, K. E.

    2006-05-01

    Endocrine disrupting compounds (EDCs) have caught recent attention as one of the major concerns in the environment. They are known to interfere with the activity of growth-related hormones and usually, as a result, cause disruption in normal functioning of the body. The compounds currently classified as EDCs range from a variety of both natural and synthetic organic compounds and also some heavy metals. Most of these compounds are used in household, pharmaceutical, industrial, agricultural activities, the consumption or usage of which increases with population. There is a lack of detailed chemical and biological analysis as to what concentrations each of these EDCs pose harmless to the environment because of the large number of the suspected compounds. However, several published reports have established that endocrine disruption is observed in aquatic species due to chronic exposure to concentrations of some EDCs as low as a few ng/l. Conventional water treatment facilities do not usually suffice to remove EDCs in concentrations below 1 ng/l. Available technologies for removal of EDCs include adsorption, degradation and membrane treatment. The removal rates, however, are dependant on the properties of the compound, such as molecular weight, water- octanol partition coefficient and vapor pressure; physiochemical conditions of the matrix such as, redox and temperature conditions; type and dose of degrading agent and the concentration of the EDCs. Since, EDCs comprise a vast variety of compounds, their response to each of these treatment methods will be different and hence it is plausible that a single treatment technique will not be sufficient to remove the EDCs to very low concentrations. Based on our review of existing water treatment methods, we believe that a sequential treatment technique that consists of an adsorption, a degradation and finally a fine membrane treatment, each optimized for favorable, efficient and inexpensive removal may be required to remove

  8. The development and endocrine functions of adipose tissue

    Technology Transfer Automated Retrieval System (TEKTRAN)

    White adipose tissue is a mesenchymal tissue that begins developing in the fetus. Classically known for storing the body’s fuel reserves, adipose tissue is now recognized as an endocrine organ. As such, the secretions from adipose tissue are known to affect several systems such as the vascular and...

  9. Endocrine dysfunction in hereditary hemochromatosis.

    PubMed

    Pelusi, C; Gasparini, D I; Bianchi, N; Pasquali, R

    2016-08-01

    Hereditary hemochromatosis (HH) is a genetic disorder of iron overload and subsequent organ damage. Five types of HH are known, classified by age of onset, genetic cause, clinical manifestations and mode of inheritance. Except for the rare form of juvenile haemochromatosis, symptoms do not usually appear until after decades of progressive iron loading and may be triggered by environmental and lifestyle factors. Despite the last decades discovery of genetic and phenotype diversity of HH, early studies showed a frequent involvement of the endocrine glands where diabetes and hypogonadism are the most common encountered endocrinopathies. The pathogenesis of diabetes is still relatively unclear, but the main mechanisms include the loss of insulin secretory capacity and insulin resistance secondary to liver damage. The presence of obesity and/or genetic predisposition may represent addictive risk factor for the development of this metabolic disease. Although old cases of primary gonad involvement are described, hypogonadism is mainly secondary to selective deposition of iron on the gonadotropin-producing cells of the pituitary gland, leading to hormonal impaired secretion. Cases of hypopituitarism or selected tropin defects, and abnormalities of adrenal, thyroid and parathyroid glands, even if rare, are reported. The prevalence of individual gland dysfunction varies enormously within studies for several bias due to small numbers of and selected cases analyzed, mixed genotypes and missing data on medical history. Moreover, in the last few years early screening and awareness of the disease among physicians have allowed hemochromatosis to be diagnosed in most cases at early stages when patients have no symptoms. Therefore, the clinical presentation of this disease has changed significantly and the recognized common complications are encountered less frequently. This review summarizes the current knowledge on HH-associated endocrinopathies. PMID:26951056

  10. Endocrine dysfunction in hereditary hemochromatosis.

    PubMed

    Pelusi, C; Gasparini, D I; Bianchi, N; Pasquali, R

    2016-08-01

    Hereditary hemochromatosis (HH) is a genetic disorder of iron overload and subsequent organ damage. Five types of HH are known, classified by age of onset, genetic cause, clinical manifestations and mode of inheritance. Except for the rare form of juvenile haemochromatosis, symptoms do not usually appear until after decades of progressive iron loading and may be triggered by environmental and lifestyle factors. Despite the last decades discovery of genetic and phenotype diversity of HH, early studies showed a frequent involvement of the endocrine glands where diabetes and hypogonadism are the most common encountered endocrinopathies. The pathogenesis of diabetes is still relatively unclear, but the main mechanisms include the loss of insulin secretory capacity and insulin resistance secondary to liver damage. The presence of obesity and/or genetic predisposition may represent addictive risk factor for the development of this metabolic disease. Although old cases of primary gonad involvement are described, hypogonadism is mainly secondary to selective deposition of iron on the gonadotropin-producing cells of the pituitary gland, leading to hormonal impaired secretion. Cases of hypopituitarism or selected tropin defects, and abnormalities of adrenal, thyroid and parathyroid glands, even if rare, are reported. The prevalence of individual gland dysfunction varies enormously within studies for several bias due to small numbers of and selected cases analyzed, mixed genotypes and missing data on medical history. Moreover, in the last few years early screening and awareness of the disease among physicians have allowed hemochromatosis to be diagnosed in most cases at early stages when patients have no symptoms. Therefore, the clinical presentation of this disease has changed significantly and the recognized common complications are encountered less frequently. This review summarizes the current knowledge on HH-associated endocrinopathies.

  11. Hybrid energy storage systems utilizing redox active organic compounds

    SciTech Connect

    Wang, Wei; Xu, Wu; Li, Liyu; Yang, Zhenguo

    2015-09-08

    Redox flow batteries (RFB) have attracted considerable interest due to their ability to store large amounts of power and energy. Non-aqueous energy storage systems that utilize at least some aspects of RFB systems are attractive because they can offer an expansion of the operating potential window, which can improve on the system energy and power densities. One example of such systems has a separator separating first and second electrodes. The first electrode includes a first current collector and volume containing a first active material. The second electrode includes a second current collector and volume containing a second active material. During operation, the first source provides a flow of first active material to the first volume. The first active material includes a redox active organic compound dissolved in a non-aqueous, liquid electrolyte and the second active material includes a redox active metal.

  12. Self-Organized Transition to Coherent Activity in Disordered Media

    NASA Astrophysics Data System (ADS)

    Singh, Rajeev; Xu, Jinshan; Garnier, Nicolas G.; Pumir, Alain; Sinha, Sitabhra

    2012-02-01

    Synchronized oscillations are of critical functional importance in many biological systems. We show that such oscillations can arise without centralized coordination in a disordered system of electrically coupled excitable and passive cells. Increasing the coupling strength results in waves that lead to coherent periodic activity, exhibiting cluster, local and global synchronization under different conditions. Our results may explain the self-organized transition in a pregnant uterus from transient, localized activity initially to system-wide coherent excitations just before delivery.

  13. ALTERATIONS IN DEVELOPMENT OF REPRODUCTIVE AND ENDOCRINE SYSTEMS OF WILDLIFE POPULATIONS EXPOSED TO ENDOCRINE-DISRUPTING CONTAMINANTS.

    EPA Science Inventory

    Wildlife and human populations are affected by contaminants in natural settings. This problem has been a growing concern over the last decade with the realization that various environmental chemicals can alter the development and functioning of endocrine organs, cells and target ...

  14. The heart as an endocrine organ.

    PubMed

    Sagnella, Guiseppe A

    2002-12-01

    The discovery of atrial natruietic peptide firmly established that the heart was not just a pump and provided the long-sought-after link between the heart and the kidney in the control of soduim balance. Pharmacological targeting of the natruiretic peptide system is now leading to novel advances in the treatment of hypertension and of heart failure - two of the most common causes of human disability and death.

  15. Removal of Biologically Active Organic Contaminants using Atomic Oxygen

    NASA Technical Reports Server (NTRS)

    Banks, Bruce A. (Inventor); Banks, Michael A. (Inventor); Banks, Eric B. (Inventor)

    2003-01-01

    Biomedical devices that are to come into contact with living tissue, such as prosthetic and other implants for the human body and the containers used to store and transport them, are together cleaned of non-living, but biologically active organic materials, including endotoxins such as lipopolysaccharides, and assembled into a hermetically sealed package without recontamination. This is achieved by cleaning both the device and package components together in an apparatus, which includes a hermetically sealed chamber, in which they are contacted with atomic oxygen which biocleans them, by oxidizing the biologically active organic materials. The apparatus also includes means for manipulating the device and container and hermetically sealing the cleaned device into the cleaned container to form the package. A calibrated witness coupon visually indicates whether or not the device and container have received enough exposure to the atomic oxygen to have removed the organic materials from their surfaces. Gamma radiation is then used to sterilize the device in the sealed container.

  16. Effects of organic dairy manure amendment on soil phosphatase activities

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Organic dairy production is increasing in the U.S. due to concerns over environmental, human, and animal health. It is well known that the application of livestock manure to soil can influence enzyme activities involved in nutrient cycling and soil fertility, such as soil phosphatases; however, orga...

  17. The Reciprocal Organization of Constructive Activity in Drug Addiction

    ERIC Educational Resources Information Center

    Akhmetzyanova, Anna I.; Nikishina, Vera B.; Klyueva, Nadezhda V.; Petrash, Ekaterina A.

    2016-01-01

    The urgency of the problem stated in the article is caused by the fact that modern scientific studies show that sustainable neuro-associative connections with the object of addiction arise at chemical addiction. The aim of this study is to examine the features of the reciprocal organization of constructive activities in drug addiction. Study of…

  18. 42 CFR 423.162 - Quality improvement organization activities.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 3 2011-10-01 2011-10-01 false Quality improvement organization activities. 423.162 Section 423.162 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM VOLUNTARY MEDICARE PRESCRIPTION DRUG BENEFIT Cost Control and Quality Improvement Requirements §...

  19. 42 CFR 423.162 - Quality improvement organization activities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Quality improvement organization activities. 423.162 Section 423.162 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM VOLUNTARY MEDICARE PRESCRIPTION DRUG BENEFIT Cost Control and Quality Improvement Requirements §...

  20. Prospective Relations between Organized Activity Participation and Psychopathology during Adolescence

    ERIC Educational Resources Information Center

    Bohnert, Amy M.; Garber, Judy

    2007-01-01

    This longitudinal study examined psychopathology as a predictor and outcome of organized activity involvement during high school among 198 adolescents who varied in risk for psychopathology as a function of their mother's depression history. Higher levels of internalizing and externalizing symptoms in eighth grade significantly predicted lower…

  1. Musculoskeletal manifestations of endocrine disorders.

    PubMed

    Boswell, Stephanie B; Patel, Dakshesh B; White, Eric A; Gottsegen, Christopher J; Forrester, Deborah M; Masih, Sulabha; Matcuk, George R

    2014-01-01

    Endocrine disorders can lead to disturbances in numerous systems within the body, including the musculoskeletal system. Radiological evaluation of these conditions can demonstrate typical appearances of the bones and soft tissues. Knowledge of these patterns can allow the radiologist to suggest a diagnosis that may not be clinically apparent. This review will highlight the typical musculoskeletal findings of acromegaly, hypercortisolism, hyperthyroidism, hypothyroidism, hyperparathyroidism, pseudo- and pseudopseudohypoparathyroidism, and diabetes mellitus. The radiological manifestations of each of these endocrine disorders, along with a brief discussion of the pathophysiology and clinical implications, will be discussed. PMID:24642251

  2. Endocrine hypertension in small animals.

    PubMed

    Reusch, Claudia E; Schellenberg, Stefan; Wenger, Monique

    2010-03-01

    Hypertension is classified as idiopathic or secondary. In animals with idiopathic hypertension, persistently elevated blood pressure is not caused by an identifiable underlying or predisposing disease. Until recently, more than 95% of cases of hypertension in humans were diagnosed as idiopathic. New studies have shown, however, a much higher prevalence of secondary causes, such as primary hyperaldosteronism. In dogs and cats, secondary hypertension is the most prevalent form and is subclassified into renal and endocrine hypertension. This review focuses on the most common causes of endocrine hypertension in dogs and cats.

  3. Endocrine Disorders in Cystic Fibrosis.

    PubMed

    Blackman, Scott M; Tangpricha, Vin

    2016-08-01

    Cystic fibrosis is frequently complicated by endocrine disorders. Diabetes can be expected to affect most with CF and pancreatic insufficiency and varies widely in age of onset, but early identification and treatment improve morbidity and mortality. Short stature can be exacerbated by relative delay of puberty and by use of inhaled corticosteroids. Bone disease in CF causes fragility fractures and should be assessed by monitoring bone mineral density and optimizing vitamin D status. Detecting and managing endocrine complications in CF can reduce morbidity and mortality in CF. These complications can be expected to become more common as the CF population ages. PMID:27469183

  4. Single-cell approaches for molecular classification of endocrine tumors

    PubMed Central

    Koh, James; Allbritton, Nancy L.; Sosa, Julie A.

    2015-01-01

    Purpose of review In this review, we summarize recent developments in single-cell technologies that can be employed for the functional and molecular classification of endocrine cells in normal and neoplastic tissue. Recent findings The emergence of new platforms for the isolation, analysis, and dynamic assessment of individual cell identity and reactive behavior enables experimental deconstruction of intratumoral heterogeneity and other contexts, where variability in cell signaling and biochemical responsiveness inform biological function and clinical presentation. These tools are particularly appropriate for examining and classifying endocrine neoplasias, as the clinical sequelae of these tumors are often driven by disrupted hormonal responsiveness secondary to compromised cell signaling. Single-cell methods allow for multidimensional experimental designs incorporating both spatial and temporal parameters with the capacity to probe dynamic cell signaling behaviors and kinetic response patterns dependent upon sequential agonist challenge. Summary Intratumoral heterogeneity in the provenance, composition, and biological activity of different forms of endocrine neoplasia presents a significant challenge for prognostic assessment. Single-cell technologies provide an array of powerful new approaches uniquely well suited for dissecting complex endocrine tumors. Studies examining the relationship between clinical behavior and tumor compositional variations in cellular activity are now possible, providing new opportunities to deconstruct the underlying mechanisms of endocrine neoplasia. PMID:26632769

  5. History of the endocrine effects of licorice.

    PubMed

    Armanini, D; Fiore, C; Mattarello, M J; Bielenberg, J; Palermo, M

    2002-09-01

    The history of licorice as an officinal plant dates back thousands of years, and licorice is still appreciated as a medicinal root. Many of its endocrine properties can be derived from observations of Authors of the ancient world, when hormones were not known. Inappropriate use of licorice can produce pseudoaldosteronism, by inactivating 11beta-hydroxysteroiod-dehydrogenase and by binding to mineralocorticoid receptors. Licorice possesses many other therapeutic properties as to potentiate the action of cortisol, to reduce testosterone synthesis, especially in women, to exert an estrogen-like activity and to reduce body fat mass. The chronological development of research on these effects is described. PMID:12373628

  6. Integrated Neural and Endocrine Control of Gastrointestinal Function.

    PubMed

    Furness, John B

    2016-01-01

    The activity of the digestive system is dynamically regulated by external factors, including body nutritional and activity states, emotions and the contents of the digestive tube. The gut must adjust its activity to assimilate a hugely variable mixture that is ingested, particularly in an omnivore such as human for which a wide range of food choices exist. It must also guard against toxins and pathogens. These nutritive and non-nutritive components of the gut contents interact with the largest and most vulnerable surface in the body, the lining of the gastrointestinal tract. This requires a gut sensory system that can detect many classes of nutrients, non-nutrient components of food, physicochemical conditions, toxins, pathogens and symbionts (Furness et al., Nat Rev Gastroenterol Hepatol 10:729-740, 2013). The gut sensors are in turn coupled to effector systems that can respond to the sensory information. The responses are exerted through enteroendocrine cells (EEC), the enteric nervous system (ENS), the central nervous system (CNS) and the gut immune and tissue defence systems. It is apparent that the control of the digestive organs is an integrated function of these effectors. The peripheral components of the EEC, ENS and CNS triumvirate are extensive. EEC cells have traditionally been classified into about 12 types (disputed in this review), releasing about 20 hormones, together making the gut endocrine system the largest endocrine organ in the body. Likewise, in human the ENS contains about 500 million neurons, far more than the number of neurons in the remainder of the peripheral autonomic nervous system. Together gut hormones, the ENS and the CNS control or influence functions including satiety, mixing and propulsive activity, release of digestive enzymes, induction of nutrient transporters, fluid transport, local blood flow, gastric acid secretion, evacuation and immune responses. Gut content receptors, including taste, free fatty acid, peptide and

  7. Endocrine and Nutritional Management After Bariatric Surgery

    MedlinePlus

    Endocrine and Nutritional Management After Bariatric Surgery A Patient’s Guide Bariatric (weight loss) surgery is a treatment ... This guide for patients is based on The Endocrine Society’s practice guidelines for physicians that focus on ...

  8. ENVIRONMENTAL ENGINEERING AND ENDOCRINE DISRUPTING CHEMICALS

    EPA Science Inventory

    Endocrine disruptors are a class of chemicals of growing interest to the environmental community. USEPA's Risk Assessment Forum defined an endocrine disrupting chemical (EDC) as "an exogenous agent that interferes with the synthesis, secretion, transport, binding, action, or elim...

  9. ANALYTICAL CHALLENGES OF ENVIRONMENTAL ENDOCRINE DISRUPTOR MONITORING

    EPA Science Inventory

    Reported increases in the incidence of endocrine-related conditions have led to speculation about environmental causes. Environmental scientists are focusing increased research effort into understanding the mechanisms by which endocrine disruptors affect human and ecological h...

  10. Why do crown ethers activate enzymes in organic solvents?

    PubMed

    van Unen, Dirk-Jan; Engbersen, Johan F J; Reinhoudt, David N

    2002-02-01

    One of the major drawbacks of enzymes in nonaqueous solvents is that their activity is often dramatically low compared to that in water. This limitation can be largely overcome by crown ether treatment of enzymes. In this paper, we describe a number of carefully designed new experiments that have improved the insights into the mechanisms that are operative in the crown ether activation of enzymes in organic solvents. The enhancement of enzyme activity upon addition of 18-crown-6 to the organic solvent can be reconciled with a mechanism in which macrocyclic interactions of 18-crown-6 with the enzyme play an important role. Macrocyclic interactions (e.g., complexation with lysine ammonium groups of the enzyme) can lead to a reduced formation of inter- and intramolecular salt bridges and, consequently, to lowering of the kinetic conformational barriers, enabling the enzyme to refold into thermodynamically stable, catalytically (more) active conformations. This assumption is supported by the observation that the crown-ether-enhanced enzyme activity is retained after removal of the crown by washing with a dry organic solvent. A much stronger crown ether activation is observed when 18-crown-6 is added prior to lyophilization, and this can be explained by a combination of two effects: the before-mentioned macrocyclic complexation effect, and a less specific, nonmacrocyclic, lyoprotecting effect. The magnitude of the total crown ether effect depends on the polarity and thermodynamic water activity of the solvent, the activation being highest in dry and apolar media, where kinetic conformational barriers are highest. By determination of the specific activity of crown-ether-lyophilized enzyme as a function of the enzyme concentration, the macrocyclic crown ether (linearly dependent on the enzyme concentration) and the nonmacrocyclic lyoprotection effect (not dependent on the enzyme concentration) could be separated. These measurements reveal that the contribution of the

  11. Environmental endocrine disruptors: Effects on the human male reproductive system.

    PubMed

    Sweeney, M F; Hasan, N; Soto, A M; Sonnenschein, C

    2015-12-01

    Incidences of altered development and neoplasia of male reproductive organs have increased during the last 50 years, as shown by epidemiological data. These data are associated with the increased presence of environmental chemicals, specifically "endocrine disruptors," that interfere with normal hormonal action. Much research has gone into testing the effects of specific endocrine disrupting chemicals (EDCs) on the development of male reproductive organs and endocrine-related cancers in both in vitro and in vivo models. Efforts have been made to bridge the accruing laboratory findings with the epidemiological data to draw conclusions regarding the relationship between EDCs, altered development and carcinogenesis. The ability of EDCs to predispose target fetal and adult tissues to neoplastic transformation is best explained under the framework of the tissue organization field theory of carcinogenesis (TOFT), which posits that carcinogenesis is development gone awry. Here, we focus on the available evidence, from both empirical and epidemiological studies, regarding the effects of EDCs on male reproductive development and carcinogenesis of endocrine target tissues. We also critique current research methodology utilized in the investigation of EDCs effects and outline what could possibly be done to address these obstacles moving forward.

  12. Environmental endocrine disruptors: Effects on the human male reproductive system.

    PubMed

    Sweeney, M F; Hasan, N; Soto, A M; Sonnenschein, C

    2015-12-01

    Incidences of altered development and neoplasia of male reproductive organs have increased during the last 50 years, as shown by epidemiological data. These data are associated with the increased presence of environmental chemicals, specifically "endocrine disruptors," that interfere with normal hormonal action. Much research has gone into testing the effects of specific endocrine disrupting chemicals (EDCs) on the development of male reproductive organs and endocrine-related cancers in both in vitro and in vivo models. Efforts have been made to bridge the accruing laboratory findings with the epidemiological data to draw conclusions regarding the relationship between EDCs, altered development and carcinogenesis. The ability of EDCs to predispose target fetal and adult tissues to neoplastic transformation is best explained under the framework of the tissue organization field theory of carcinogenesis (TOFT), which posits that carcinogenesis is development gone awry. Here, we focus on the available evidence, from both empirical and epidemiological studies, regarding the effects of EDCs on male reproductive development and carcinogenesis of endocrine target tissues. We also critique current research methodology utilized in the investigation of EDCs effects and outline what could possibly be done to address these obstacles moving forward. PMID:26847433

  13. RELATIVE BINDING AFFINITY OF ENDOCRINE DISRUPTING CHEMICALS TO ESTROGEN RECEPTOR IN TWO SPECIES OF FRESHWATER FISH

    EPA Science Inventory

    The US EPA has been mandated to screen industrial chemicals and pesticides for potential endocrine activity. To evaluate the potential for chemicals to cause endocrine disruption in fish we have previously measured the affinity of a number of chemicals for the rainbow trout estr...

  14. DETERMINING INDICATORS OF EXPOSURE AND EFFECTS FOR ENDOCRINE DISRUPTING CHEMICALS (EDCS): AN OVERVIEW.

    EPA Science Inventory

    Endocrine disruptors are characterized by their influence on animal endocrine systems resulting in reproductive, developmental, neurological, and immune dysfunction. The purpose of this overview is to provide the reader with a sense of the activities within the U.S. Environmental...

  15. PROGRESS IN THE OECD WORK ON ENDOCRINE DISRUPTORS TESTING AND ASSESSMENT FOR ENVIRONMENTAL SPECIES

    EPA Science Inventory

    The OECD Special Activity on endocrine disruptors testing and assessment (EDTA) started in 1996 at the request of member countries and industry with the objective to develop test methods for the detection and characterization of endocrine disrupting chemicals. The purpose of the ...

  16. Precommitment low-level Neurog3 expression defines a long-lived mitotic endocrine-biased progenitor pool that drives production of endocrine-committed cells.

    PubMed

    Bechard, Matthew E; Bankaitis, Eric D; Hipkens, Susan B; Ustione, Alessandro; Piston, David W; Yang, Yu-Ping; Magnuson, Mark A; Wright, Christopher V E

    2016-08-15

    The current model for endocrine cell specification in the pancreas invokes high-level production of the transcription factor Neurogenin 3 (Neurog3) in Sox9(+) bipotent epithelial cells as the trigger for endocrine commitment, cell cycle exit, and rapid delamination toward proto-islet clusters. This model posits a transient Neurog3 expression state and short epithelial residence period. We show, however, that a Neurog3(TA.LO) cell population, defined as Neurog3 transcriptionally active and Sox9(+) and often containing nonimmunodetectable Neurog3 protein, has a relatively high mitotic index and prolonged epithelial residency. We propose that this endocrine-biased mitotic progenitor state is functionally separated from a pro-ductal pool and endows them with long-term capacity to make endocrine fate-directed progeny. A novel BAC transgenic Neurog3 reporter detected two types of mitotic behavior in Sox9(+) Neurog3(TA.LO) progenitors, associated with progenitor pool maintenance or derivation of endocrine-committed Neurog3(HI) cells, respectively. Moreover, limiting Neurog3 expression dramatically increased the proportional representation of Sox9(+) Neurog3(TA.LO) progenitors, with a doubling of its mitotic index relative to normal Neurog3 expression, suggesting that low Neurog3 expression is a defining feature of this cycling endocrine-biased state. We propose that Sox9(+) Neurog3(TA.LO) endocrine-biased progenitors feed production of Neurog3(HI) endocrine-committed cells during pancreas organogenesis. PMID:27585590

  17. Refractory Organic Compounds in Enceladus' Ice Grains and Hydrothermal Activity

    NASA Astrophysics Data System (ADS)

    Postberg, F.; Khawaja, N.; Hsu, H. W.; Sekine, Y.; Shibuya, T.

    2015-12-01

    Cassini's Cosmic Dust Analyzer (CDA) generates time-of-flight mass spectra of individual grains impinging on the instruments target-plate. Following the analysis of salt rich ice grains emitted by Enceladus that indicated a salt-water ocean in contact with the moon's rocky core [1,2] a recent CDA analysis of nano-phase silica particles pointed at hydrothermal activity at the moon's rock/water interface [3]. The results imply temperatures above 80 - 90°C and alkaline pH values around 10 reminiscent of alkaline hydrothermal vents on Earth like the Lost City Hydrothermal Field. In this context the compositional analysis of organic components in CDA mass spectra of the ejected ice grains is of particular relevance. A multitude of volatile organic species has already been identified in the gas component of the plume [4]. As expected, we find more complex organic molecules in ice grains than in the gas indicating aromatic species, amines, and carbonyl group species. The composition of organic-bearing ice grains displays a great diversity indicating a variety of different organic species in varying concentrations. Recent spatially resolved CDA in situ measurements inside Enceladus' plume indicate that these organic compounds are especially frequent in 'young' ice grains that have just been ejected by high velocity jets. We investigate the implications of our findings with respect to ice grain formation at the water surface and inside the icy vents. We constrain the generation of organic compounds at the rock/water interface in the light of hydrothermal activity and the potential for the formation of life precursor molecules in Enceladus' ocean. Ref:[1] Postberg et al., Nature 459, 1098-1101 (2009). [2] Postberg et al., Nature 474, 620-622 (2011). [3]. Hsu, Postberg, Sekine et al., Nature, 519, 207-210 (2015). [4] Waite et al., Nature 460, 487-490 (2009).

  18. Laminated active matrix organic light-emitting devices

    NASA Astrophysics Data System (ADS)

    Liu, Hongyu; Sun, Runguang

    2008-02-01

    Laminated active matrix organic light-emitting device (AMOLED) realizing top emission by using bottom-emitting organic light-emitting diode (OLED) structure was proposed. The multilayer structure of OLED deposited in the conventional sequence is not on the thin film transistor (TFT) backplane but on the OLED plane. The contact between the indium tin oxide (ITO) electrode of TFT backplane and metal cathode of OLED plane is implemented by using transfer electrode. The stringent pixel design for aperture ratio of the bottom-emitting AMOLED, as well as special technology for the top ITO electrode of top-emitting AMOLED, is unnecessary in the laminated AMOLED.

  19. [Endocrine abnormalities in HIV infections].

    PubMed

    Verges, B; Chavanet, P; Desgres, J; Kisterman, J P; Waldner, A; Vaillant, G; Portier, H; Brun, J M; Putelat, R

    The finding of endocrine gland lesions at pathological examination in AIDS and reports of several cases of endocrine disease in patients with this syndrome have prompted us to study endocrine functions in 63 patients (51 men, 12 women) with HIV-1 infection. According to the Center for Disease Control (CDC) classification system, 13 of these patients were stage CDC II, 27 stage CDC III and 23 stage CDC IV. We explored the adrenocortical function (ACTH, immediate tetracosactrin test) and the thyroid function (free T3 and T4 levels, TRH on TSH test) in all 63 patients. The hypothalamic-pituitary-gonadal axis (testosterone levels, LHRH test) and prolactin secretion (THR test) were explored in the 51 men. The results obtained showed early peripheral testicular insufficiency at stage CDC II and early pituitary gland abnormalities with hypersecretion of ACTH and prolactin also at stage CDC II. On the other hand, adrenocortical and pituitary abnormalities were not frequently found. The physiopathology of the endocrine abnormalities observed in HIV-1-infected patients remains unclear, but one may suspect that it involves interleukin-1 since this protein factor has recently been shown to stimulate the corticotropin-releasing hormone secretion and to act directly on the glycoprotein capsule of the virus (gp 120) whose structure is similar to that of some neurohormones.

  20. CURRENT CHALLENGES ON ENDOCRINE DISRUPTORS

    EPA Science Inventory

    For over ten years, major international efforts have been aimed at understanding the mechanism and extent of endocrine disruption in experimental models, wildlife, and people; the occurrence of this in the real world and in developing tools for screening and prediction of risk. ...

  1. The Vitamin D Endocrine System.

    ERIC Educational Resources Information Center

    Norman, Anthony W.

    1985-01-01

    Discusses the physiology and biochemistry of the vitamin D endocrine system, including role of biological calcium and phosphorus, vitamin D metabolism, and related diseases. A 10-item, multiple-choice test which can be used to obtain continuing medical education credit is included. (JN)

  2. Test Driving ToxCast: Endocrine Profiling for 1858 Chemicals Included in Phase II

    PubMed Central

    Filer, Dayne; Patisaul, Heather B.; Schug, Thaddeus; Reif, David; Thayer, Kristina

    2014-01-01

    Identifying chemicals, beyond those already implicated, to test for potential endocrine disruption is a challenge and high throughput approaches have emerged as a potential tool for this type of screening. This review focused the Environmental Protection Agency’s (EPA) ToxCast™ high throughput in vitro screening (HTS) program. Utility for identifying compounds was assessed and reviewed by using it to run the recently expanded chemical library (from 309 compounds to 1858) through the ToxPi™ prioritization scheme for endocrine disruption. The analysis included metabolic and neuroendocrine targets. This investigative approach simultaneously assessed the utility of ToxCast, and helped identify novel chemicals which may have endocrine activity. Results from this exercise suggest the spectrum of environmental chemicals with potential endocrine activity is much broader than indicated, and that some aspects of endocrine disruption are not fully covered in ToxCast. PMID:25460227

  3. Ultraviolet filters differentially impact the expression of key endocrine and stress genes in embryos and larvae of Chironomus riparius.

    PubMed

    Ozáez, Irene; Morcillo, Gloria; Martínez-Guitarte, José-Luis

    2016-07-01

    Several organic UV filters have hormonal activity in vertebrates, as demonstrated in fishes, rodents and human cells. Despite the accumulation of filter contaminants in aquatic systems, research on their effects on the endocrine systems of freshwaters invertebrates is scarce. In this work, the effects of five frequently used UV filters were investigated in embryos and larvae of Chironomus riparius, which is a reference organism in ecotoxicology. LC50 values for larvae as well as the percentage of eclosion of eggs were determined following exposures to: octyl-p-methoxycinnamate (OMC) also known as 2-ethylhexyl-4-methoxycinnamate (EHMC); 4-methylbenzylidene camphor (4MBC); 4-hydroxybenzophenone (4HB); octocrylene (OC); and octyldimethyl-p-aminobenzoate (OD-PABA). To assess sublethal effects, expression levels of the genes coding for the ecdysone receptor (EcR) and heat shock protein HSP70 were investigated as biomarkers for endocrine and stress effects at the cellular level. Life-stage-dependent sensitivity was found. In embryos, all of the UV filters provoked a significant overexpression of EcR at 24h after exposure. OC, 4MBC and OD-PABA also triggered transcriptional activation of the hsp70 stress gene in embryos. In contrast, in larvae, only 4MBC and OMC/EHMC increased EcR and hsp70 mRNA levels and OD-PABA upregulated only the EcR gene. These results revealed that embryos are particularly sensitive to UV filters, which affect endocrine regulation during development. Most UV filters also triggered the cellular stress response, and thus exhibit proteotoxic effects. The differences observed between embryos and larvae and the higher sensitivity of embryos highlight the importance of considering different life stages when evaluating the environmental risks of pollutants, particularly when analyzing endocrine effects. PMID:26994811

  4. Ultraviolet filters differentially impact the expression of key endocrine and stress genes in embryos and larvae of Chironomus riparius.

    PubMed

    Ozáez, Irene; Morcillo, Gloria; Martínez-Guitarte, José-Luis

    2016-07-01

    Several organic UV filters have hormonal activity in vertebrates, as demonstrated in fishes, rodents and human cells. Despite the accumulation of filter contaminants in aquatic systems, research on their effects on the endocrine systems of freshwaters invertebrates is scarce. In this work, the effects of five frequently used UV filters were investigated in embryos and larvae of Chironomus riparius, which is a reference organism in ecotoxicology. LC50 values for larvae as well as the percentage of eclosion of eggs were determined following exposures to: octyl-p-methoxycinnamate (OMC) also known as 2-ethylhexyl-4-methoxycinnamate (EHMC); 4-methylbenzylidene camphor (4MBC); 4-hydroxybenzophenone (4HB); octocrylene (OC); and octyldimethyl-p-aminobenzoate (OD-PABA). To assess sublethal effects, expression levels of the genes coding for the ecdysone receptor (EcR) and heat shock protein HSP70 were investigated as biomarkers for endocrine and stress effects at the cellular level. Life-stage-dependent sensitivity was found. In embryos, all of the UV filters provoked a significant overexpression of EcR at 24h after exposure. OC, 4MBC and OD-PABA also triggered transcriptional activation of the hsp70 stress gene in embryos. In contrast, in larvae, only 4MBC and OMC/EHMC increased EcR and hsp70 mRNA levels and OD-PABA upregulated only the EcR gene. These results revealed that embryos are particularly sensitive to UV filters, which affect endocrine regulation during development. Most UV filters also triggered the cellular stress response, and thus exhibit proteotoxic effects. The differences observed between embryos and larvae and the higher sensitivity of embryos highlight the importance of considering different life stages when evaluating the environmental risks of pollutants, particularly when analyzing endocrine effects.

  5. The endocrine system and sarcopenia: potential therapeutic benefits.

    PubMed

    McIntire, Kevin L; Hoffman, Andrew R

    2011-12-01

    Age related muscle loss, known as sarcopenia, is a major factor in disability, loss of mobility and quality of life in the elderly. There are many proposed mechanisms of age-related muscle loss that include the endocrine system. A variety of hormones regulate growth, development and metabolism throughout the lifespan. Hormone activity may change with age as a result of reduced hormone secretion or decreased tissue responsiveness. This review will focus on the complex interplay between the endocrine system, aging and skeletal muscle and will present possible benefits of therapeutic interventions for sarcopenia.

  6. Insect-plant interactions: endocrine defences.

    PubMed

    Bowers, W S

    1984-01-01

    It is the inevitable consequence of evolution that competitive species living together in a restricted space must try to exclude each other. Plants and insects are prime examples of this eternal competition, and although neither of these is in danger of extinction, their mutual defensive strategies are of compelling interest to the human race. Plant defences based on the insecticidal activity of certain of their secondary chemicals are readily apparent. Only through research into the fundamentals of insect physiology and biochemistry are more subtle defensive mechanisms revealed, linked to the disruption of the insect endocrine system. A diverse number of chemical structures are found in plants, which interfere with hormone-mediated processes in insects. Examples include: mimics of the insect's juvenile hormones such as juvabione from the balsam fir and the juvocimenes from sweet basil, which lethally disrupt insect development, and the precocenes found in Ageratum species, which act as anti-juvenile hormonal agents. The latter appear to serve as 'suicide substrates', undergoing activation into cytotoxins when acted on by specialized enzymes resident in the insect endocrine gland (corpus allatum) that is responsible for juvenile hormone biosynthesis and secretion. Consideration of these plant defensive strategies, which have been reached through aeons of evolutionary experimentation, may assist the human race in its defences against its principal competitors for food, fibre and health.

  7. Impact of Physical Exercise on Endocrine Aging.

    PubMed

    Janssen, Joseph A M J L

    2016-01-01

    Physical exercise may be vital to the maintenance of the endocrine system with aging and its helps to restore loss of activity of the endocrine system with aging. There is evidence that physical exercise induces activity of the growth hormone-insulin-like growth factor-1 axis and so produces anabolic effects in skeletal muscles. Mechano growth factor (MGF), a locally produced isoform of IGF-1, has been hypothesized to be important for the maintenance of skeletal muscles with aging. Short-term high-resistance exercise results in an increase of MGF mRNA in young but not in elderly subjects. Reported changes in levels of circulating sex steroid hormones in men after different types of (acute and chronic) physical exercise are mixed and not consistent. In addition, physical exercise may increase local effects of sex steroid hormones, and this may be more important than levels of circulating sex steroids for the maintenance and function of skeletal muscles. In elderly women, both increased physical exercise and reduced body fat may decrease levels of circulating sex hormones. Aging is further associated with changes in the dynamic functions of the hypothalamic-pituitary axis, but these changes may be attenuated/modified by aerobic training. Chronic exercise does not alter circulating cortisol levels in elderly subjects. PMID:27348867

  8. Endocrine modulation of the adolescent brain: a review.

    PubMed

    Vigil, Pilar; Orellana, Renán F; Cortés, Manuel E; Molina, Carmen T; Switzer, Barbara E; Klaus, Hanna

    2011-12-01

    Neurophysiological and behavioral development is particularly complex in adolescence. Youngsters experience strong emotions and impulsivity, reduced self-control, and preference for actions which offer immediate rewards, among other behavioral patterns. Given the growing interest in endocrine effects on adolescent central nervous system development and their implications on later stages of life, this article reviews the effects of gonadal steroid hormones on the adolescent brain. These effects are classified as organizational, the capacity of steroids to determine nervous system structure during development, and activational, the ability of steroids to modify nervous activity to promote certain behaviors. During transition from puberty to adolescence, steroid hormones trigger various organizational phenomena related to structural brain circuit remodelling, determining adult behavioral response to steroids or sensory stimuli. These changes account for most male-female sexual dimorphism. In this stage sex steroids are involved in the main functional mechanisms responsible for organizational changes, namely myelination, neural pruning, apoptosis, and dendritic spine remodelling, activated only during embryonic development and during the transition from puberty to adolescence. This stage becomes a critical organizational window when the appropriately and timely exerted functions of steroid hormones and their interaction with some neurotransmitters on adolescent brain development are fundamental. Thus, understanding the phenomena linking steroid hormones and adolescent brain organization is crucial in the study of teenage behavior and in later assessment and treatment of anxiety, mood disorders, and depression. Adolescent behavior clearly evidences a stage of brain development influenced for the most part by steroid hormones.

  9. Self-organization via active exploration in robotic applications

    NASA Technical Reports Server (NTRS)

    Ogmen, H.; Prakash, R. V.

    1992-01-01

    We describe a neural network based robotic system. Unlike traditional robotic systems, our approach focussed on non-stationary problems. We indicate that self-organization capability is necessary for any system to operate successfully in a non-stationary environment. We suggest that self-organization should be based on an active exploration process. We investigated neural architectures having novelty sensitivity, selective attention, reinforcement learning, habit formation, flexible criteria categorization properties and analyzed the resulting behavior (consisting of an intelligent initiation of exploration) by computer simulations. While various computer vision researchers acknowledged recently the importance of active processes (Swain and Stricker, 1991), the proposed approaches within the new framework still suffer from a lack of self-organization (Aloimonos and Bandyopadhyay, 1987; Bajcsy, 1988). A self-organizing, neural network based robot (MAVIN) has been recently proposed (Baloch and Waxman, 1991). This robot has the capability of position, size rotation invariant pattern categorization, recognition and pavlovian conditioning. Our robot does not have initially invariant processing properties. The reason for this is the emphasis we put on active exploration. We maintain the point of view that such invariant properties emerge from an internalization of exploratory sensory-motor activity. Rather than coding the equilibria of such mental capabilities, we are seeking to capture its dynamics to understand on the one hand how the emergence of such invariances is possible and on the other hand the dynamics that lead to these invariances. The second point is crucial for an adaptive robot to acquire new invariances in non-stationary environments, as demonstrated by the inverting glass experiments of Helmholtz. We will introduce Pavlovian conditioning circuits in our future work for the precise objective of achieving the generation, coordination, and internalization

  10. Developmental effects of endocrine-disrupting chemicals in wildlife and humans

    SciTech Connect

    Colborn, T. ); vom Saal, F.S. ); Soto, A.M. )

    1993-10-01

    Large numbers and large quantities of endoncrine-disrupting chemicals have been released into the environment since World War II. Many of these chemicals can disturb development of the endocrine system and of the organs that respond to endocrine signals in organisms indirectly exposed during prenatal and/or early postnatal life; effects of exposure during development are permanent and irreversible. The risk to the developing organism can also stem from direct exposure of the offspring after birth or hatching. In addition, trangenerational exposure can result from the exposure of the mother to a chemical at any time throughout her life before producing offspring due to persistent of endocrine-disrupting chemicals in body fat, which is mobilized during egg laying or pregnancy and lactation. Mechanisms underlying the disruption of the development of vital systems, such as the endocrine, reproductive, and immune systems, are discussed with reference to wildlife, laboratory animals, and humans.

  11. Endocrine and Metabolic Disorders

    MedlinePlus

    ... Main Navigation Home Preface & Reader's Guide Introduction Population Characteristics Health Status Health Behaviors Health Indicators Self-Reported Health Status Life Expectancy Leading Causes of Death Activity Limitations and ...

  12. Spontaneous neuronal activity as a self-organized critical phenomenon

    NASA Astrophysics Data System (ADS)

    de Arcangelis, L.; Herrmann, H. J.

    2013-01-01

    Neuronal avalanches are a novel mode of activity in neuronal networks, experimentally found in vitro and in vivo, and exhibit a robust critical behaviour. Avalanche activity can be modelled within the self-organized criticality framework, including threshold firing, refractory period and activity-dependent synaptic plasticity. The size and duration distributions confirm that the system acts in a critical state, whose scaling behaviour is very robust. Next, we discuss the temporal organization of neuronal avalanches. This is given by the alternation between states of high and low activity, named up and down states, leading to a balance between excitation and inhibition controlled by a single parameter. During these periods both the single neuron state and the network excitability level, keeping memory of past activity, are tuned by homeostatic mechanisms. Finally, we verify if a system with no characteristic response can ever learn in a controlled and reproducible way. Learning in the model occurs via plastic adaptation of synaptic strengths by a non-uniform negative feedback mechanism. Learning is a truly collective process and the learning dynamics exhibits universal features. Even complex rules can be learned provided that the plastic adaptation is sufficiently slow.

  13. Effects of organic carbon sequestration strategies on soil enzymatic activities

    NASA Astrophysics Data System (ADS)

    Puglisi, E.; Suciu, N.; Botteri, L.; Ferrari, T.; Coppolecchia, D.; Trevisan, M.; Piccolo, A.

    2009-04-01

    Greenhouse gases emissions can be counterbalanced with proper agronomical strategies aimed at sequestering carbon in soils. These strategies must be tested not only for their ability in reducing carbon dioxide emissions, but also for their impact on soil quality: enzymatic activities are related to main soil ecological quality, and can be used as early and sensitive indicators of alteration events. Three different strategies for soil carbon sequestration were studied: minimum tillage, protection of biodegradable organic fraction by compost amendment and oxidative polimerization of soil organic matter catalyzed by biometic porfirins. All strategies were compared with a traditional agricultural management based on tillage and mineral fertilization. Experiments were carried out in three Italian soils from different pedo-climatic regions located respectively in Piacenza, Turin and Naples and cultivated with maize or wheat. Soil samples were taken for three consecutive years after harvest and analyzed for their content in phosphates, ß-glucosidase, urease and invertase. An alteration index based on these enzymatic activities levels was applied as well. The biomimetic porfirin application didn't cause changes in enzymatic activities compared to the control at any treatment or location. Enzymatic activities were generally higher in the minimum tillage and compost treatment, while differences between location and date of samplings were limited. Application of the soil alteration index based on enzymatic activities showed that soils treated with compost or subjected to minimum tillage generally have a higher biological quality. The work confirms the environmental sustainability of the carbon sequestering agronomical practices studied.

  14. Orientations of psychotic activity in defensive pathological organizations.

    PubMed

    Williams, Paul

    2014-06-01

    The author reviews some clinical experiences of the treatment of personality disordered patients suffering from internal domination of ego functioning by a defensive pathological organization. In particular, the function and purpose of perverse, sadistic attacks by the organization on the ego are considered and questions pertaining to technique are raised. It is suggested that different forms of sadistic, subjugating activity by pathological organizations may denote differences in intent borne of the type and severity of the psychopathology of the individual. Patients with severe narcissistic psychopathology for whom object contact has become associated with the arousal of intense psychotic anxieties seem more likely to be subjected to an invasive, annihilatory imperative by the pathological organization, the purpose of which appears to be to obliterate the experience of contact with any differentiated object, to avoid emotion and to use coercion to enforce a primitive identification by the ego with the psychotic organization in the mind. Certain patients with less severe narcissistic psychopathology, yet for whom object contact can also be associated with the arousal of psychotic anxieties due to intense or persistent conflict with the object, sometimes expressed as organized sadomasochistic clinging to a punishing and punished object (for example, in certain borderline or depressed patients) exhibit sadistic attacks that serve less to annihilate object contact and more to intrusively control and punish the object. Observations of these phenomena have been made by a number of psychoanalysts in recent decades and these contributions are discussed. This paper is addressed primarily to the implications for technique with such patients, particularly a need for triangulation of their experiences of oppression in order to loosen the controls over the ego by the pathological organization. PMID:24620792

  15. Turing patterns in network-organized activator-inhibitor systems

    NASA Astrophysics Data System (ADS)

    Nakao, Hiroya; Mikhailov, Alexander S.

    2010-07-01

    Turing instability in activator-inhibitor systems provides a paradigm of non-equilibrium self-organization; it has been extensively investigated for biological and chemical processes. Turing instability should also be possible in networks, and general mathematical methods for its treatment have been formulated previously. However, only examples of regular lattices and small networks were explicitly considered. Here we study Turing patterns in large random networks, which reveal striking differences from the classical behaviour. The initial linear instability leads to spontaneous differentiation of the network nodes into activator-rich and activator-poor groups. The emerging Turing patterns become furthermore strongly reshaped at the subsequent nonlinear stage. Multiple coexisting stationary states and hysteresis effects are observed. This peculiar behaviour can be understood in the framework of a mean-field theory. Our results offer a new perspective on self-organization phenomena in systems organized as complex networks. Potential applications include ecological metapopulations, synthetic ecosystems, cellular networks of early biological morphogenesis, and networks of coupled chemical nanoreactors.

  16. Bone endocrine regulation of energy metabolism and male reproduction.

    PubMed

    Karsenty, Gerard

    2011-10-01

    Usually vertebrate physiology is studied within the confined limits of a given organ, if not cell type. This approach has progressively changed with the emergence of mouse genetics that has rejuvenated the concept of a whole body study of physiology. A vivid example of how mouse genetics has profoundly affected our understanding of physiology is skeleton physiology. A genetic approach to bone physiology revealed that bone via osteocalcin, an osteoblast-secreted molecule, is a true endocrine organ regulating energy metabolism and male reproduction. This ongoing body of work that takes bone out of its traditional roles is connecting it to a growing number of peripheral organs. These novel important hormonal connections between bone, energy metabolism and reproduction underscore the concept of functional dependence in physiology and the importance of genetic approaches to identify novel endocrine regulations.

  17. Water Activity Limits the Hygroscopic Growth Factor of Organic Aerosols

    NASA Astrophysics Data System (ADS)

    Rodriguez, L. I.; Cabrera, J. A.; Golden, D.; Tabazadeh, A.

    2007-12-01

    In this work we study the hygroscopic behavior of organic aerosols, which has important implications for Earth's climate. The hygroscopic growth factor (HGF) is defined as the ratio of the diameter of a spherical particle when it is exposed to dry conditions to that at humid conditions. We present a new formulation to express the HGF of an aerosol particle as a function of water activity (aw) in the aqueous phase. This new formulation matches reported HGFs for common inorganic salts and water-miscible organic particles that are known to deliquesce into aqueous drops at high relative humidities (RH). Many studies use tandem differential mobility analyzers (TDMA) to determine the HGF of organic aerosols. For example, Brooks et al. used a TDMA to measure a HGF of 1.2 for 2 μm phthalic acid (PA) particles at 90% RH (aw= 0.9). However, water activity limits the growth of a particle that can be attributed to water uptake. We have assembled a vapor pressure apparatus to measure aw of aqueous solutions at room temperature. Measured water activities for PA, used in our growth formulation, yield a HGF of ~ 1.0005 for 2 μm PA particles at 90% RH. Comparing our results against Brooks et al. suggests that TDMA experiments may grossly overestimate the HGF of PA particles since water activity limits this growth to below 1.0005. Alternatively, we suggest that the adsorption of a negligible mass of water by a highly porous PA particle can lead to an apparent growth in particle size by changing its morphology. Other studies also use TDMAs to measure HGFs of secondary organic aerosols (SOAs). HGFs reported for SOAs are very similar to PA, suggesting that the observed growth may be due to morphological changes in particle size rather than water uptake as commonly assumed. We built a smog chamber where an organic precursor, such as d-limonene, reacts with nitrogen oxides under UV radiation to produce SOAs. We compare the HGFs for SOAs obtained with our method to those obtained with

  18. Constitutive Ret activity in knock-in multiple endocrine neoplasia type B mice induces profound elevation of brain dopamine concentration via enhanced synthesis and increases the number of TH-positive cells in the substantia nigra.

    PubMed

    Mijatovic, Jelena; Airavaara, Mikko; Planken, Anu; Auvinen, Petri; Raasmaja, Atso; Piepponen, T Petteri; Costantini, Frank; Ahtee, Liisa; Saarma, Mart

    2007-05-01

    Ret is the common signaling receptor for glial cell line-derived neurotrophic factor (GDNF) and other ligands of the GDNF family that have potent effects on brain dopaminergic neurons. The Met918Thr mutation leads to constitutive activity of Ret receptor tyrosine kinase, causing the cancer syndrome called multiple endocrine neoplasia type B (MEN2B). We used knock-in MEN2B mice with the Ret-MEN2B mutation to study the effects of constitutive Ret activity on the brain dopaminergic system and found robustly increased concentrations of dopamine (DA) and its metabolites in the striatum, cortex, and hypothalamus. The concentrations of brain serotonin were not affected and those of noradrenaline were slightly increased only in the lower brainstem. Tyrosine hydroxylase (TH) protein levels were increased in the striatum and substantia nigra/ventral tegmental area (SN/VTA), and TH mRNA levels were increased in SN/VTA of MEN2B mice, suggesting that constitutive Ret activity increases DA levels by increasing its synthesis. Also, the striatal DA transporter protein levels in the MEN2B mice were increased, which agrees with increased sensitivity of these mice to the stimulatory effects of cocaine. In the SN pars compacta of homozygous MEN2B mice, we found a 26% increase in the number of TH-positive cells, but no differences were found in the VTA. Thus, we show here that the constitutive Ret activity in mice is sufficient to increase the number of dopaminergic neurons and leads to profound elevation of brain DA concentration. These data clearly suggest that Ret activity per se can have a direct biological function that actively changes and shapes the brain dopaminergic system. PMID:17475787

  19. Cloud condensation nuclei activity of isoprene secondary organic aerosol

    NASA Astrophysics Data System (ADS)

    Engelhart, Gabriella J.; Moore, Richard H.; Nenes, Athanasios; Pandis, Spyros N.

    2011-01-01

    This work explores the cloud condensation nuclei (CCN) activity of isoprene secondary organic aerosol (SOA), likely a significant source of global organic particulate matter and CCN, produced from the oxidation with OH from HONO/HOOH photolysis in a temperature-controlled SOA chamber. CCN concentrations, activation diameter, and droplet growth kinetic information were monitored as a function of supersaturation (from 0.3% to 1.5%) for several hours using a cylindrical continuous-flow streamwise thermal gradient CCN counter connected to a scanning mobility particle sizer. The initial SOA concentrations ranged from 2 to 30 μg m-3 and presented CCN activity similar to monoterpene SOA with an activation diameter of 35 nm for 1.5% supersaturation and 72 nm for 0.6% supersaturation. The CCN activity improved slightly in some experiments as the SOA aged chemically and did not depend significantly on the level of NOx during the SOA production. The measured activation diameters correspond to a hygroscopicity parameter κ value of 0.12, similar to κ values of 0.1 ± 0.04 reported for monoterpene SOA. Analysis of the water-soluble carbon extracted from filter samples of the SOA suggest that it has a κ of 0.2-0.3 implying an average molar mass between 90 and 150 g mol-1 (assuming a zero and 5% surface tension reduction with respect to water, respectively). These findings are consistent with known oxidation products of isoprene. Using threshold droplet growth analysis, the CCN activation kinetics of isoprene SOA was determined to be similar to pure ammonium sulfate aerosol.

  20. Determination of endocrine disrupting compounds using temperature-dependent inclusion chromatography: II. Fast screening of free steroids and related low-molecular-mass compounds fraction in the environmental samples derived from surface waters, treated and untreated sewage waters as well as activated sludge material.

    PubMed

    Zarzycki, Paweł K; Włodarczyk, Elzbieta; Baran, Michał J

    2009-10-30

    In the present work solid-phase extraction protocol based on C18 tubes and organic water washing solvents as well as isocratic HPLC procedure focused on quantification of free steroids and related low-molecular-mass endocrine disrupting compounds (EDCs), characterized by different polarity varied from estetrol to progesterone, were studied. Described separation method involves temperature-dependent inclusion chromatography with mobile phase modified with beta-cyclodextrin. Using such analytical approach the environmental samples derived from Baltic Sea, selected lakes and rivers of the Middle Pomerania in northern part of Poland as well as untreated and treated sewage water from municipal sewage treatment plant near Koszalin were analyzed. Moreover, some preliminary data concerning estriol, testosterone and equilin biodegradation involving activated sludge material were reported. Cluster and principal components analysis of the acquired data sets confirms a high separation and quantification throughput of the solid-phase extraction and isocratic HPLC protocols presented. The method can be useful for simple and rapid classification of the environmental samples characterized by different sources of EDCs loading. The results of this work extend the utility of temperature-dependent inclusion chromatography as an inexpensive, efficient and accurate analytical tool appropriate for characterisation and quantification of complex environmental samples. PMID:19356767

  1. Patterns of Adolescents' Participation in Organized Activities: Are Sports Best when Combined with Other Activities?

    ERIC Educational Resources Information Center

    Linver, Miriam R.; Roth, Jodie L.; Brooks-Gunn, Jeanne

    2009-01-01

    Although many adolescents participate in sports and other types of organized activities, little extant research explores how youth development outcomes may vary for youth involved in different combinations of activities. The present study uses the Child Development Supplement of the Panel Study of Income Dynamics, a large, nationally…

  2. Optogenetically enhanced pituitary corticotroph cell activity post-stress onset causes rapid organizing effects on behaviour.

    PubMed

    De Marco, Rodrigo J; Thiemann, Theresa; Groneberg, Antonia H; Herget, Ulrich; Ryu, Soojin

    2016-01-01

    The anterior pituitary is the major link between nervous and hormonal systems, which allow the brain to generate adequate and flexible behaviour. Here, we address its role in mediating behavioural adjustments that aid in coping with acutely threatening environments. For this we combine optogenetic manipulation of pituitary corticotroph cells in larval zebrafish with newly developed assays for measuring goal-directed actions in very short timescales. Our results reveal modulatory actions of corticotroph cell activity on locomotion, avoidance behaviours and stimulus responsiveness directly after the onset of stress. Altogether, the findings uncover the significance of endocrine pituitary cells for rapidly optimizing behaviour in local antagonistic environments. PMID:27646867

  3. Optogenetically enhanced pituitary corticotroph cell activity post-stress onset causes rapid organizing effects on behaviour

    PubMed Central

    De Marco, Rodrigo J.; Thiemann, Theresa; Groneberg, Antonia H.; Herget, Ulrich; Ryu, Soojin

    2016-01-01

    The anterior pituitary is the major link between nervous and hormonal systems, which allow the brain to generate adequate and flexible behaviour. Here, we address its role in mediating behavioural adjustments that aid in coping with acutely threatening environments. For this we combine optogenetic manipulation of pituitary corticotroph cells in larval zebrafish with newly developed assays for measuring goal-directed actions in very short timescales. Our results reveal modulatory actions of corticotroph cell activity on locomotion, avoidance behaviours and stimulus responsiveness directly after the onset of stress. Altogether, the findings uncover the significance of endocrine pituitary cells for rapidly optimizing behaviour in local antagonistic environments. PMID:27646867

  4. [The informative mechanisms of systemic organization of psychic activity].

    PubMed

    Sudakov, K V

    2012-01-01

    In this review on the basis of functional systems theory developed by P. Anokhin theoretical approaches to informative mechanisms of systemic organization of psychic activity are presented. Author formulates the conception on discrete system quantums of psychic and behavioral activity from needs to its satisfaction and develops its informative equivalents. It was shown that informative equivalents of needs and its satisfaction are reflected in structures of action acceptors in the form of dynamic informative images. On the basis of acceptors of results of action informative systemic quantums are developed which constantly control its manifestation in behavioral systemic quantums. Informative systemic quantums are extracted in advance by predominate motivations and are associated with negative emotions of needs and positive emotions of their satisfaction. The content of this review confirms I.P. Pavlov's foresight on possible confluence of material and idealistic processes in psychic human activity.

  5. Multiple endocrine neoplasia type 2.

    PubMed

    Lodish, Maya

    2013-01-01

    Multiple endocrine neoplasia type 2 (MEN2) is an autosomal-dominant cancer syndrome characterized by variable penetrance of medullary thyroid carcinoma(MTC), pheochromocytoma (PHEO), and primary hyperparathyroidism (PHPT). MEN2 consists of two clinical subtypes, MEN2A and MEN2B. Familial medullary thyroid cancer is now viewed as a phenotypic variant of MEN2A with decreased penetrance for PHEO and PHPT rather than a distinct entity. All subtypes are caused by gain-of-function mutations of the RET proto-oncogene. Genotype-phenotype correlations exist that help predict the presence of other associated endocrine neoplasms as well as the timing of thyroid cancer development. Recognition of the clinical entity in individuals and families at risk of harboring a germline RET mutation is crucial for the management and prevention of associated malignancies. Recent guidelines released by the American Thyroid Association regarding the management of MTC will be summarized in this chapter.

  6. Classical endocrine diseases causing obesity.

    PubMed

    Weaver, Jolanta U

    2008-01-01

    Obesity is associated with several endocrine diseases, including common ones such as hypothyroidism and polycystic ovarian syndrome to rare ones such as Cushing's syndrome, central hypothyroidism and hypothalamic disorders. The mechanisms for the development of obesity vary in according to the endocrine condition. Hypothyroidism is associated with accumulation of hyaluronic acid within various tissues, additional fluid retention due to reduced cardiac output and reduced thermogenesis. The pathophysiology of obesity associated with polycystic ovarian syndrome remains complex as obesity itself may simultaneously be the cause and the effect of the syndrome. Net excess of androgen appears to be pivotal in the development of central obesity. In Cushing's syndrome, an interaction with thyroid and growth hormones plays an important role in addition to an increased adipocyte differentiation and adipogenesis. This review also describes remaining rare cases: hypothalamic obesity due to central hypothyroidism and combined hormone deficiencies. PMID:18230905

  7. Male reprotoxicity and endocrine disruption

    PubMed Central

    Campion, Sarah; Catlin, Natasha; Heger, Nicholas; McDonnell, Elizabeth V.; Pacheco, Sara E.; Saffarini, Camelia; Sandrof, Moses A.; Boekelheide, Kim

    2013-01-01

    Mammalian reproductive tract development is a tightly regulated process that can be disrupted following exposure to drugs, toxicants, endocrine disrupting chemicals or other compounds via alterations to gene and protein expression or epigenetic regulation. Indeed, the impacts of developmental exposure to certain toxicants may not be fully realized until puberty or adulthood when the reproductive tract becomes sexually mature and altered functionality is manifested. Exposures that occur later in life, once development is complete, can also disrupt the intricate hormonal and paracrine interactions responsible for adult functions, such as spermatogenesis. In this chapter, the biology and toxicology of the male reproductive tract is explored, proceeding through the various life stages including in utero development, puberty, adulthood and senescence. Special attention is given to the discussion of endocrine disrupting chemicals, chemical mixtures, low dose effects, transgenerational effects, and potential exposure-related causes of male reproductive tract cancers. PMID:22945574

  8. Endocrine therapy of breast cancer

    SciTech Connect

    Cavalli, F.

    1986-01-01

    This book results from a meeting of the ESO (European School of Oncology) Task Force on endocrine aspects of breast cancer. The contributions stem from some of the most outstanding researchers in Europe and highlight mainly methodological issues and new avenues for future research. The chapters on basic research deal primarily with experimental strategies for studying the relationship between steroid hormones, growth factors, and oncongenes. The clinically oriented chapters treat the methodology of clinical trials. Provocative questions are raised, such as: What are the pitfalls in endocrine trials. What does statistical proof mean. How can we consider a quality of life endpoint in the adjuvant setting. Two special reports deal with the controversial issues of chemoprevention in high-risk normal women and the optimization of the hormonal contribution to the adjuvant therapy of breast cancer. Topics considered included oncogenic transformations, radiotherapy, steroid hormones, cell proliferation, tamoxifen, and preventive medicine.

  9. SEQUESTERING AGENTS FOR ACTIVE CAPS - REMEDIATION OF METALS AND ORGANICS

    SciTech Connect

    Knox, A; Michael Paller, M; Danny D. Reible, D; Xingmao Ma, X; Ioana G. Petrisor, I

    2007-05-10

    This research evaluated organoclays, zeolites, phosphates, and a biopolymer as sequestering agents for inorganic and organic contaminants. Batch experiments were conducted to identify amendments and mixtures of amendments for metal and organic contaminants removal and retention. Contaminant removal was evaluated by calculating partitioning coefficients. Metal retention was evaluated by desorption studies in which residue from the removal studies was extracted with 1 M MgCl{sub 2} solution. The results indicated that phosphate amendments, some organoclays, and the biopolymer, chitosan, were very effective sequestering agents for metals in fresh and salt water. Organoclays were very effective sorbents for phenanthrene, pyrene, and benzo(a)pyrene. Partitioning coefficients for the organoclays were 3000-3500 ml g{sup -1} for benzo(a)pyrene, 400-450 ml g{sup -1} for pyrene, and 50-70 ml g{sup -1} for phenanthrene. Remediation of sites with a mixture of contaminants is more difficult than sites with a single contaminant because metals and organic contaminants have different fate and transport mechanisms in sediment and water. Mixtures of amendments (e.g., organoclay and rock phosphate) have high potential for remediating both organic and inorganic contaminants under a broad range of environmental conditions, and have promise as components in active caps for sediment remediation.

  10. Impact of endocrine disruptors on ovarian steroidogenesis.

    PubMed

    Mlynarcikova, A; Fickova, M; Scsukova, S

    2014-10-01

    Production of steroid hormones by the ovary plays a key role in the female phenotype maintenance, as well as is critical for regular ovarian processes, including follicle growth, oocyte maturation and ovulation. Thus, optimal ovarian steroid synthesis is an indispensable requisite for the female reproductive health. In the past decades, along with an increased incidence of female reproductive disorders, an increasing concern for the potential reproductive impact of exogenous factors, particularly of environmental pollutants with endocrine disrupting properties, has risen. The scientific studies report that ovarian steroid hormone production is being recognized as an important target for the action of endocrine disrupting chemicals (EDCs). The fact that these chemicals have been detected in the biological samples of general population, and even directly in the follicular fluid of women, emphasizes the demands for testing the influence of EDCs on ovarian steroidogenesis. For these purposes, different methodological approaches have been employed, from in vivo studies on female rodents to in vitro experimental procedures using steroidogenically active follicular cells. In the present review, the effects of selected EDCs (pesticides, phthalate and phenol derivatives, and halogenated arylhydrocarbons) on the processes of ovarian steroidogenesis are summarized, and possible mechanisms of action of these agents are outlined.

  11. Ferrocene Functionalized Endocrine Modulators as Anticancer Agents

    NASA Astrophysics Data System (ADS)

    Hillard, Elizabeth A.; Vessières, Anne; Jaouen, Gerard

    We present here some of our studies on the synthesis and behaviour of ferrocenyl selective endocrine receptor modulators against cancer cells, particularly breast and prostate cancers. The proliferative/anti-proliferative effects of compounds based on steroidal and non-steroidal endocrine modulators have been extensively explored in vitro. Structure-activity relationship studies of such molecules, particularly the hydroxyferrocifens and ferrocene phenols, have shown the effect of (1) the presence and the length of the N,N-dimethylamino side chain, (2) the presence and position of the phenol group, (3) the role of the ferrocenyl moiety, (4) that of conjugation, (5) phenyl functionalisation and (6) the placement of the phenyl group. Compounds possessing a ferrocene moiety linked to a p-phenol by a conjugated π-system are among the most potent of the series, with IC50 values ranging from 0.090 to 0.6µM on hormone independent breast cancer cells. Based on the SAR data and electrochemical studies, we have proposed an original mechanism to explain the unusual behaviour of these bioorganometallic species and coin the term "kronatropic" to qualify this effect, involving ROS production and bio-oxidation. In addition, the importance of formulation is underlined. We also discuss the behaviour of ferrocenyl androgens and anti-androgens for possible use against prostate cancers. In sum, ferrocene has proven to be a fascinating substituent due to its vast potential for oncology.

  12. Endocrine Factors Modulating Immune Responses in Pregnancy

    PubMed Central

    Schumacher, Anne; Costa, Serban-Dan; Zenclussen, Ana Claudia

    2014-01-01

    How the semi-allogeneic fetus is tolerated by the maternal immune system remains a fascinating phenomenon. Despite extensive research activity in this field, the mechanisms underlying fetal tolerance are still not well understood. However, there are growing evidences that immune–immune interactions as well as immune–endocrine interactions build up a complex network of immune regulation that ensures fetal survival within the maternal uterus. In the present review, we aim to summarize emerging research data from our and other laboratories on immune modulating properties of pregnancy hormones with a special focus on progesterone, estradiol, and human chorionic gonadotropin. These pregnancy hormones are critically involved in the successful establishment, maintenance, and termination of pregnancy. They suppress detrimental maternal alloresponses while promoting tolerance pathways. This includes the reduction of the antigen-presenting capacity of dendritic cells (DCs), monocytes, and macrophages as well as the blockage of natural killer cells, T and B cells. Pregnancy hormones also support the proliferation of pregnancy supporting uterine killer cells, retain tolerogenic DCs, and efficiently induce regulatory T (Treg) cells. Furthermore, they are involved in the recruitment of mast cells and Treg cells into the fetal–maternal interface contributing to a local accumulation of pregnancy-protective cells. These findings highlight the importance of endocrine factors for the tolerance induction during pregnancy and encourage further research in the field. PMID:24847324

  13. Growing new endocrine pancreas in situ.

    PubMed

    Hammerman, Marc R

    2006-03-01

    Type 1 diabetes mellitus is a major cause of endstage renal disease in young adults. Maintenance of normoglycemia in type 1 diabetics using exogenous insulin is difficult under the best of circumstances. Transplantation therapies are limited by the scarcity of human donor organs, rendering a priority the identification of an alternative source for replacing insulin-secreting cells. Embryonic pancreatic primordia transplanted into diabetic animal hosts undergo selective endocrine differentiation in situ and normalize glucose tolerance. Pancreatic primordia can be transplanted across isogeneic, allogeneic, and both concordant (rat-to-mouse) and highly disparate (pig-to-rodent) xenogeneic barriers. Successful transplantation of pancreatic primordia depends on obtaining them at defined windows during embryonic development within which the risk of teratogenicity is eliminated, growth potential is maximized, and immunogenicity is reduced. Here we review studies exploring the potential for pancreatic organogenesis post-transplantation of embryonic primordia as a therapy for type 1 diabetes.

  14. Endocrine abnormalities of obesity.

    PubMed

    Björntorp, P

    1995-09-01

    Studies have shown that patients with central obesity have increased cortisol secretion, probably because they have increased activity of the hypothalamic-pituitary-adrenal (HPA) axis. A high waist-to-hip ratio (WHR) is associated with low production of sex steroids, such as testosterone in men, and a low rate of secretion of growth hormone. High levels of cortisol and insulin combined with low levels of growth hormone and sex steroid can cause lipid accumulation. These hormonal changes probably produce more deposition of visceral than subcutaneous fat. Patients who are deficient in either testosterone or growth hormone show a reduction in visceral adiposity when their hormone levels are normalized. Stress has been shown to activate the HPA axis and may cause the hormonal changes associated with obesity. Individuals with elevated WHR have indications of high levels of stress and anxiety. Monkeys that were stressed by social disruption were found to have increased cortisol levels and low sex steroid levels. Many of these animals had insulin resistance and visceral adiposity. Stimulants, such as alcohol and smoking, also increase the activity of the HPA axis.

  15. Endocrine manifestations in celiac disease

    PubMed Central

    Freeman, Hugh James

    2016-01-01

    Celiac disease (CD) is an autoimmune small intestinal mucosal disorder that often presents with diarrhea, malabsorption and weight loss. Often, one or more associated endocrine disorders may be associated with CD. For this review, methods involved an extensive review of published English-language materials. In children and adolescents, prospective studies have demonstrated a significant relationship to insulin-dependent or type 1 diabetes, whereas in adults, autoimmune forms of thyroid disease, particularly hypothyroidism, may commonly co-exist. In some with CD, multiple glandular endocrinopathies may also occur and complicate the initial presentation of the intestinal disease. In others presenting with an apparent isolated endocrine disorder, serological screening for underlying subclinical CD may prove to be positive, particularly if type 1 diabetes, autoimmune thyroid or other autoimmune endocrine diseases, such as Addison’s disease are first detected. A number of reports have also recorded hypoparathyroidism or hypopituitarism or ovarian failure in CD and these may be improved with a strict gluten-free diet. PMID:27784959

  16. [Contamination, endocrine disruptors and cancer].

    PubMed

    Arvelo, Francisco; Sojo, Felipe; Cotte, Carlos

    2016-03-01

    Since the mid-twentieth century, many species, very different from each other and located in all areas and comers of the planet, began presenting various alterations, many of which suggested to be related to endocrine disorders. Research has shown that such alterations were caused by exposure to various chemical contaminants that could affect the health and cause serious illnesses. Among them stands a diverse and large group of compounds, with very different chemical structures, capable of altering the hormonal balance, act at very low doses and with different mechanisms of action, that are called "endocrine disrupting chemicals". When released into the environment or as part of objects, food or medicines, constitute a major risk to animals and humans, which produces not only endocrine dysfunctions but also different cancers, which include the most common types. Despite the importance and significance of the impact of these compounds, they are not sufficiently known or understood, so the aim of this review is to show their origin and impact in the field of human health, highlighting their role as inducers of cancer, which has led to multiple clinical and biological investigations. PMID:27382804

  17. Fundamental differences in the neural invasion behavior of pancreatic endocrine tumors: relevance for local recurrence rates?

    PubMed

    Bergmann, Frank; Ceyhan, Güralp O; Rieker, Ralf J; Esposito, Irene; Fischer, Lars; Herpel, Esther; Friess, Helmut; Schirmacher, Peter; Kern, Michael A

    2009-01-01

    Neural invasion represents an important prognostic factor in pancreatic cancer, and it is thought to be one of the main causes for the high rate of postoperative local recurrences in pancreatic ductal adenocarcinomas. In contrast to the latter, systematic investigations of the mode and extent of neural invasion in pancreatic endocrine tumors have not yet been carried out, although this process represents an important feature in the classification of these tumors. In the present study, a total of 48 pancreatic endocrine tumors were analyzed including 10 well-differentiated endocrine tumors of uncertain behavior, 33 well-differentiated endocrine carcinomas, and 5 poorly differentiated endocrine carcinomas. Neural invasion was found in a large subset (73%) of pancreatic endocrine tumors. The frequency of neural invasion correlated with the grade of malignancy but occurred irrespective of functional activity, hormone phenotype, or histomorphology. Analogous to pancreatic ductal adenocarcinoma, the expression of epidermal growth factor receptor and nerve growth factor, which were expressed in 50% and 100% of the tumors, respectively, seemed to be associated with the frequency of neural invasion. However, in contrast to pancreatic ductal adenocarcinoma, neural invasion in pancreatic endocrine