Clinical outcome and patient satisfaction using biodegradable (NasoPore) and non-biodegradable packing, a double-blind, prospective, randomized study.

PubMed

Burduk, Pawel Krzysztof; Wierzchowska, Malgorzata; Grześkowiak, Blazej; Kaźmierczak, Wojciech; Wawrzyniak, Katarzyna

Nasal packing after endoscopic sinus surgery is used as a standard procedure. The optimum solution to minimize or eliminate all disadvantages of this procedure may be accomplished using biodegradable packs. The aim of this study was to compare patient satisfaction and clinical outcome associated with absorbable and non-absorbable packing after FESS. In total, 50 patients were included in a prospective, double-blind, randomized trial. One side was packed with polyurethane foam, while the opposite side was packed with gauze packing. On the 2nd, 10th, and 30th postoperative day, the patients were questioned with the aid of a visual analog scale. The standardized questionnaires for bleeding, nasal breathing, feeling of pressure, and headache were used. The presence of synechiae, infection, or granulation was noted and recorded with the video-endoscopy. A significant difference according to lower pressure was found in the NasoPore group compared to the controls on day ten after surgery. The NasoPore packing had lower scores with respect to postoperative nose blockage on the 2nd and 10th days. Mucosal healing was better for the NasoPore group, both at day ten and 30 compared with the control group. The overall patient comfort is higher when using NasoPore compared to non-resorbable traditional impregnated gauze packing. Intensive saline douches applied three to four times per day are mandatory after the operation to prevent synechiae formation and fluid resorption by the packing. Published by Elsevier Editora Ltda.

Novel use of tissue expander for dilation of oropharyngeal stenosis.

PubMed

Banerjee, Debdeep; Wang, James C; Demke, Joshua C

2014-11-01

Naso/oropharyngeal stenoses are uncommon surgical complications. We present a child having undergone previous adenoidectomy without complication who developed naso/oropharyngeal scarring after subsequent tonsillectomy. She presented with nasal obstruction and frequent gasping at night worrisome for obstructive sleep apnea. Scar was initially excised and the defect allografted. Conventional esophageal dilators were undersized, and ultimately a tissue expander was used intraoperatively as a balloon dilator. The patient's symptoms and sleep apnea resolved. We found use of a tissue expander as a balloon dilator to be at least minimally effective in dilating the oropharynx when all other methods at our disposal proved ineffective. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Neuro-Modulation of Immuno-Endocrine Response Induced by Kaliotoxin of Androctonus Scorpion Venom.

PubMed

Ladjel-Mendil, Amina; Martin-Eauclaire, Marie-France; Laraba-Djebari, Fatima

2016-12-01

Kaliotoxin (KTX), a specific blocker of potassium channels, exerts various toxic effects due to its action on the central nervous system. Its use in experimental model could help the understanding of the cellular and molecular mechanisms involved in the neuropathological processes related to potassium channel dysfunctions. In this study, the ability of KTX to stimulate neuro-immuno-endocrine axis was investigated. As results, the intracerebroventricular injection of KTX leads to severe structural-functional alterations of both hypothalamus and thyroid. These alterations were characterized by a massive release of hormones' markers of thyroid function associated with damaged tissue which was infiltrated by inflammatory cell and an imbalanced redox status. Taken together, these data highlight that KTX is able to modulate the neuro-endocrine response after binding to its targets leading to the hypothalamus and the thyroid stimulation, probably by inflammatory response activation and the installation of oxidative stress in these organs. © 2016 Wiley Periodicals, Inc.

Scientists find promising predictor of HPV-related oropharynx cancer

Cancer.gov

Researchers have found that antibodies against the human papillomavirus (HPV) may help identify individuals who are at greatly increased risk of HPV-related cancer of the oropharynx, which is a portion of the throat that contains the tonsils.

Biomechanical investigation of naso-orbitoethmoid trauma by finite element analysis.

PubMed

Huempfner-Hierl, Heike; Schaller, Andreas; Hemprich, Alexander; Hierl, Thomas

2014-11-01

Naso-orbitoethmoid fractures account for 5% of all facial fractures. We used data derived from a white 34-year-old man to make a transient dynamic finite element model, which consisted of about 740 000 elements, to simulate fist-like impacts to this anatomically complex area. Finite element analysis showed a pattern of von Mises stresses beyond the yield criterion of bone that corresponded with fractures commonly seen clinically. Finite element models can be used to simulate injuries to the human skull, and provide information about the pathogenesis of different types of fracture. Copyright © 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Paclitaxel and Carboplatin Before Radiation Therapy With Paclitaxel in Treating HPV-Positive Patients With Stage III-IV Oropharynx, Hypopharynx, or Larynx Cancer

ClinicalTrials.gov

2017-04-19

Human Papilloma Virus Infection; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Verrucous Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Verrucous Carcinoma of the Larynx

Foreign body in ear, nose and oropharynx: experience from a tertiary hospital.

PubMed

Tiago, Romualdo Suzano Louzeiro; Salgado, Daniel Cauduro; Corrêa, Juliano Piotto; Pio, Márcio Ricardo Barros; Lambert, Ernani Edney

2006-01-01

The occurrence of foreign bodies in otorhinolaryngology is reason of constant searches for emergency services. To value the incidence of patients with foreign body, to analyze the clinical situation and the treatment in these cases. The prospective study was realized in 81 patients with diagnosis of foreign body of nose, ear or oropharynx in the otorhinolaryngology service of the Hospital do Servidor Público Municipal de São Paulo between april/2003 and march/2005. 57 cases of foreign body of ear, 13 cases of nose and 11 of oropharynx. These patients, 51.85% were men and 48.15% were women. The age average was 23 years old. The average of the evolution time was 18.36 days, being that 38.27% these cases were taken care in less 24 hours of evolution. Inside the total of patients, 83.95% received initial attendance in the otorhinolaryngology clinic, and 16.05% came of another service after some previous removal attempt. The most common symptom of the foreign bodies cases of oropharynx it was odinofagia present in 90.91% of the cases; in the foreign bodies of nose, the unilateral rhinorrhea and cacosmia were present in 46.15 of the cases; in the foreign bodies of ear, 38.60% evolved without symptoms and 28.07 with hipoacusia. The most frequent foreign body of oropharynx it was the fish spine (54.55%); in the nose it was the paper (30.77%); and in the ear it was the cotton (31.58%). The complications resulting of the presence of foreign body or about the manipulation of these had been found in 13 cases (16.05%). Most cases of foreign body conditions, in which a non-specialist professional or a non-professional person previously handles its removal, have a bad evolution with emerging complications. Such outcomes strengthen the fact that an otorhinolaryngologist using the proper equipment must treat patients with foreign body.

EPIGENETIC TRANSGENERATIONAL ACTIONS OF ENDOCRINE DISRUPTORS

PubMed Central

Skinner, Michael K.; Manikkam, Mohan; Guerrero-Bosagna, Carlos

2010-01-01

Environmental factors have a significant impact on biology. Therefore, environmental toxicants through similar mechanisms can modulate biological systems to influence physiology and promote disease states. The majority of environmental toxicants do not have the capacity to modulate DNA sequence, but can alter the epigenome. In the event an environmental toxicant such as an endocrine disruptor modifies the epigenome of a somatic cell, this may promote disease in the individual exposed, but not be transmitted to the next generation. In the event a toxicant modifies the epigenome of the germ line permanently, then the disease promoted can become transgenerationaly transmitted to subsequent progeny. The current review focuses on the ability of environmental factors such as endocrine disruptors to promote transgenerational phenotypes. PMID:21055462

K3Na(SO4)2 : Eu nanoparticles for high dose of ionizing radiation

NASA Astrophysics Data System (ADS)

Sahare, P. D.; Ranjan, Ranju; Salah, Numan; Lochab, S. P.

2007-02-01

K3Na(SO4)2 : Eu nanocrystalline powder was synthesized by the chemical co-precipitation method. The x-ray diffraction pattern of the nanomaterials shows a hexagonal structure for its crystals having grain size of ~28 nm. Transmission electron microscopy revealed that the K3Na(SO4)2 : Eu nanoparticles are single crystals with almost a uniform shape and size. Thermoluminescence (TL) was taken after irradiating the samples at various exposures of γ-rays from a 60Co source. A prominent TL glow peak is observed at 423 K along with three small peaks/shoulders at around 382, 460 and 509 K. The observed TL sensitivity of the prepared nanocrystalline powder is around 4 times more than that of LiF : Mg,Ti (TLD-100) phosphor. The 423 K peak of the nanomaterial phosphor eventually shows a near linear response with exposures increasing up to very high values (as high as 70 kGy), where all the other TLD phosphors saturate. This property along with its other desired properties such as high sensitivity, relatively simple glow curve structure and low fading makes the nanocrystalline phosphor a suitable dosimeter to estimate low as well as high exposures of γ-rays. TL analysis using the glow curve deconvolution technique was also done for determining different trapping parameters.

ENDOCRINE DISRUPTORS FROM COMBUSTION AND VEHICULAR EMISSIONS: IDENTIFICATION AND SOURCE NOMINATION

EPA Science Inventory

During the last decade, concerns have been raised regarding the possible harmful effects of exposure to certain chemicals that are capable of modulating or disrupting the function of the endocrine system. These chemicals, which are referred to as endocrine disrupting chemicals (E...

Monte Carlo evaluation of RapidArc™ oropharynx treatment planning strategies for sparing of midline structures

NASA Astrophysics Data System (ADS)

Bush, K.; Zavgorodni, S.; Gagne, I.; Townson, R.; Ansbacher, W.; Beckham, W.

2010-08-01

The aim of the study was to perform the Monte Carlo (MC) evaluation of RapidArc™ (Varian Medical Systems, Palo Alto, CA) dose calculations for four oropharynx midline sparing planning strategies. Six patients with squamous cell cancer of the oropharynx were each planned with four RapidArc head and neck treatment strategies consisting of single and double photon arcs. In each case, RTOG0522 protocol objectives were used during planning optimization. Dose calculations performed with the analytical anisotropic algorithm (AAA) are compared against BEAMnrc/DOSXYZnrc dose calculations for the 24-plan dataset. Mean dose and dose-to-98%-of-structure-volume (D98%) were used as metrics in the evaluation of dose to planning target volumes (PTVs). Mean dose and dose-to-2%-of-structure-volume (D2%) were used to evaluate dose differences within organs at risk (OAR). Differences in the conformity index (CI) and the homogeneity index (HI) as well as 3D dose distributions were also observed. AAA calculated PTV mean dose, D98%, and HIs showed very good agreement with MC dose calculations within the 0.8% MC (statistical) calculation uncertainty. Regional node volume (PTV-80%) mean dose and D98% were found to be overestimated (1.3%, σ = 0.8% and 2.3%, σ = 0.8%, respectively) by the AAA with respect to MC calculations. Mean dose and D2% to OAR were also observed to be consistently overestimated by the AAA. Increasing dose calculation differences were found in planning strategies exhibiting a higher overall fluence modulation. From the plan dataset, the largest local dose differences were observed in heavily shielded regions and within the esophageal and sinus cavities. AAA dose calculations as implemented in RapidArc™ demonstrate excellent agreement with MC calculations in unshielded regions containing moderate inhomogeneities. Acceptable agreement is achieved in regions of increased MLC shielding. Differences in dose are attributed to inaccuracies in the AAA-modulated fluence

Correlation between CD4 count and intensity of Candida colonization in the oropharynx of HIV-infected/ AIDS patient.

PubMed

Bandar, Ivo Novita Sah; Widodo, Djoko; Djauzi, Samsuridjal; Muthalib, Abdul; Soegondo, Sidartawan; Wahyuningsih, Retno

2006-01-01

To know the correlation between CD4 count and intensity of Candida colonizations in the oropharynx of HIV-infected/AIDS patients, to get the prevalence of oropharyngeal candidiasis (OPC), and to know what kind of Candida species that causes oropharynx candidiasis of HIV-infected/AIDS patients. A cross-sectional study was conducted in HIV-infected/AIDS patients who came as outpatients and inpatients in Cipto Mangunkusumo Hospital. The patients were interviewed, physically examined, their CD4 counts were checked, and their mouth rinse samples were taken to be cultured. Candida species was identified in CHROMagar media, and data were processed. From September 2004 until January 2005, 60 HIV-infected/AIDS patients were included in this study. There were 86.7% males and 13.3% females. Majority of the patients were from 20-30 years age group (85%). The most frequent transmission was among drug users (75%) followed by sexual contact (18.3%). The median of CD4 counts was 100 cells/il, ranged from 2 to 842 cells/il. Proportion of the OPC was 63.3% (CI 95% = 51.1 - 75.5). From 59 Candida isolates in this study, 74.58% were C. albicans. Candida non C. albicans species that were found in this trial were C. krusei, C. parapsilosis and C. tropicalis. There was significant correlation between low CD4 counts and high intensity of Candida colonization on the oropharynx of the subjects (r = -0.756). There was strong negative correlation (r = -0.756) between CD4 count and intensity of Candida colonization in the oropharynx of HIV-infected/AIDS patients. Proportion of OPC in this study was 63.3%. The most frequent species found in the oropharynx of the subjects was C. albicans.

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.

Long term results of postoperative Intensity-Modulated Radiation Therapy (IMRT) in the treatment of Squamous Cell Carcinoma (SCC) located in the oropharynx or oral cavity.

PubMed

Hoffmann, M; Saleh-Ebrahimi, L; Zwicker, F; Haering, P; Schwahofer, A; Debus, J; Huber, P E; Roeder, F

2015-12-04

To report our long-term results with postoperative intensity-modulated radiation therapy (IMRT) in patients suffering from squamous-cell carcinoma (SCC) of the oral cavity or oropharynx. Seventy five patients were retrospectively analyzed. Median age was 58 years and 84 % were male. 76 % of the primaries were located in the oropharynx. Surgery resulted in negative margins (R0) in 64 % of the patients while 36 % suffered from positive margins (R1). Postoperative stages were as follows: stage 1:4 %, stage 2:9 %, stage 3:17 %, stage 4a:69 % with positive nodes in 84 %. Perineural invasion (Pn+) and extracapsular extension (ECE) were present in 7 % and 29 %, respectively. All patients received IMRT using the step-and-shoot approach with a simultaneously integrated boost (SIB) in 84 %. Concurrent systemic therapy was applied to 53 patients, mainly cisplatin weekly. Median follow-up was 55 months (5-150). 13 patients showed locoregional failures (4 isolated local, 4 isolated neck, 5 combined) transferring into 5-year-LRC rates of 85 %. Number of positive lymph nodes (n > 2) and presence of ECE were significantly associated with decreased LRC in univariate analysis, but only the number of nodes remained significant in multivariate analysis. Overall treatment failures occurred in 20 patients (9 locoregional only, 7 distant only, 4 combined), transferring into 3-and 5-year-FFTF rates of 77 % and 75 %, respectively. The 3-and 5-year-OS rates were 80 % and 72 %, respectively. High clinical stage, high N stage, number of positive nodes (n > 2), ECE and Pn1 were significantly associated with worse FFTF and OS in univariate analysis, but only number of nodes remained significant for FFTF in multivariate analysis. Maximum acute toxicity was grade 3 in 64 % and grade 4 in 1 %, mainly hematological or mucositis/dysphagia. Maximum late toxicity was grade 3 in 23 % of the patients, mainly long-term tube feeding dependency. Postoperative IMRT achieved excellent LRC and good OS

[Prevalence of human papillomavirus infection in squamous cell carcinoma of the oral cavity, oropharynx and larynx].

PubMed

Villagómez-Ortíz, Vicente José; Paz-Delgadillo, Diana Estela; Marino-Martínez, Iván; Ceseñas-Falcón, Luis Ángel; Sandoval-de la Fuente, Anabel; Reyes-Escobedo, Alfonso

2016-01-01

Cancer of the head and neck comprises a group of neoplasms that share a similar anatomical origin. Most originate from the epithelium of the aerodigestive tract and 90% correspond to squamous cell carcinoma. In the last 15 years, an increase in the incidence of squamous cell carcinoma induced by human papillomavirus (HPV) has been seen, mainly types 16 and 18, which are the most frequent found in cancers of the oral cavity and oropharynx, and types 6 and 11 in laryngeal cancer. There are reports in the literature that show HPV as the leading cause of oropharyngeal squamous cell carcinoma. Determine the prevalence of infection with high-risk HPV in patients diagnosed with squamous cell carcinoma of the oral cavity, oropharynx and larynx. An observational, cross-sectional, descriptive, unblinded study was performed. Prevalence of HPV infection was determined by polymerase chain reaction (PCR) in DNA samples from tumour tissue of patients with squamous cell carcinoma of the oral cavity, oropharynx and larynx. Typing was subsequently performed in HPV positive samples in order to detect types 18, 16, 11 and 6, using custom primers. A total of 45 patients were included. The association between laryngeal squamous cell carcinoma and HPV was established in two patients, which represented an overall prevalence of 4.4% in our population, and 10% for laringeal tumours. There is a low prevalence of HPV infection in squamous cell carcinoma of the oral cavity, oropharynx and larynx, in our population. Prospective studies on younger patients could provide more information. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

Plasma biomarkers in juvenile marine fish provide evidence for endocrine modulation potential of organotin compounds.

PubMed

Min, Byung Hwa; Kim, Bo-Mi; Kim, Moonkoo; Kang, Jung-Hoon; Jung, Jee-Hyun; Rhee, Jae-Sung

2018-08-01

Organotin compounds, such as tributyltin (TBT) and triphenyltin (TPT), have been widely used to control marine fouling. Here, we show that organotin stimulation reduces the hormone levels in the plasma of two economically important aquaculture fish. Blood plasma samples were collected from juvenile red seabream and black rockfish exposed to environmentally realistic concentrations of TBT and TPT for 14 days. The levels of two plasma biomarkers, namely the yolk protein precursor vitellogenin (VTG) and the sex steroid 17β-estradiol (E2), were measured to determine the endocrine disrupting potential of the organotin compounds. Both organotin compounds were dose-dependently accumulated in the blood of two fish. Exposure to waterborne TBT and TBT significantly decreased the plasma VTG levels in both the juvenile fish in a dose-dependent manner. In contrast, the treatment with E2, a well-known VTG inducer, significantly increased the plasma VTG levels in both the fish. In addition, the mRNA levels of vtg were also downregulated in the liver tissues of both the fish at 100 and/or 1000 ng L -1 of TBT or TPT exposure. The plasma E2 titers were significantly suppressed at 100 and/or 1000 ng L -1 of TBT or TPT exposure for 14 days compared to their titer in the control. Since estrogen directly regulates vtg gene expression and VTG synthesis, our results reveal the endocrine disrupting potential of organotin compounds, and subsequently the endocrine modulation at early stage of fish can trigger further fluctuations in sexual differentiation, maturation, sex ration or egg production. In addition, the results demonstrate their effects on non-target organisms, particularly on animals reared in aquaculture and fisheries. Copyright © 2018 Elsevier Inc. All rights reserved.

Use of the probiotic Lactobacillus plantarum 299 to reduce pathogenic bacteria in the oropharynx of intubated patients: a randomised controlled open pilot study

PubMed Central

Klarin, Bengt; Molin, Göran; Jeppsson, Bengt; Larsson, Anders

2008-01-01

Introduction Ventilator-associated pneumonia (VAP) is usually caused by aspiration of pathogenic bacteria from the oropharynx. Oral decontamination with antiseptics, such as chlorhexidine (CHX) or antibiotics, has been used as prophylaxis against this complication. We hypothesised that the probiotic bacteria Lactobacillus plantarum 299 (Lp299) would be as efficient as CHX in reducing the pathogenic bacterial load in the oropharynx of tracheally intubated, mechanically ventilated, critically ill patients. Methods Fifty critically ill patients on mechanical ventilation were randomised to either oral mechanical cleansing followed by washing with 0.1% CHX solution or to the same cleansing procedure followed by oral application of an emulsion of Lp299. Samples for microbiological analyses were taken from the oropharynx and trachea at inclusion and at defined intervals thereafter. Results Potentially pathogenic bacteria that were not present at inclusion were identified in oropharyngeal samples from eight of the patients treated with Lp299 and 13 of those treated with CHX (p = 0.13). Analysis of tracheal samples yielded similar results. Lp299 was recovered from the oropharynx of all patients in the Lp299 group. Conclusions In this pilot study, we found no difference between the effect of Lp299 and CHX used in oral care procedures, when we examined the effects of those agents on colonisation of potentially pathogenic bacteria in the oropharynx of intubated, mechanically ventilated patients. PMID:18990201

Modulation of Food Reward by Endocrine and Environmental Factors: Update and Perspective.

PubMed

Figlewicz, Dianne P

2015-01-01

Palatable foods are frequently high in energy density. Chronic consumption of high-energy density foods can contribute to the development of cardiometabolic pathology including obesity, diabetes, and cardiovascular disease. This article reviews the contributions of extrinsic and intrinsic factors that influence the reward components of food intake. A narrative review was conducted to determine the behavioral and central nervous system (CNS) related processes involved in the reward components of high-energy density food intake. The rewarding aspects of food, particularly palatable and preferred foods, are regulated by CNS circuitry. Overlaying this regulation is modulation by intrinsic endocrine systems and metabolic hormones relating to energy homeostasis, developmental stage, or gender. It is now recognized that extrinsic or environmental factors, including ambient diet composition and the provocation of stress or anxiety, also contribute substantially to the expression of food reward behaviors such as motivation for, and seeking of, preferred foods. High-energy density food intake is influenced by both physiological and pathophysiological processes. Contextual, behavioral, and psychological factors and CNS-related processes represent potential targets for multiple types of therapeutic intervention.

ACTOplus Met XR in Treating Patients With Stage I-IV Oral Cavity or Oropharynx Cancer Undergoing Definitive Treatment | Division of Cancer Prevention

Cancer.gov

This randomized phase IIb trial studies how well ACTOplus met XR works in treating in patients with stage I-IV oral cavity or oropharynx cancer that are undergoing definitive treatment. Chemoprevention is the use of drugs to keep oral cavity or oropharynx cancer from forming or coming back. The use of ACTOplus met XR may slow disease progression in patients with oral cavity or

Human papillomavirus-associated oropharynx cancer (HPV-OPC): treatment options.

PubMed

Chau, Nicole G; Rabinowits, Guilherme; Haddad, Robert I

2014-12-01

Human papillomavirus-associated oropharynx cancer (HPV-OPC) is growing in incidence and has distinct clinical, pathologic, molecular, and epidemiologic features. However, the management of HPV-OPC does not presently differ from HPV-negative OPC based on the current evidence and requires complex multidisciplinary approaches. The superior prognosis of HPV-OPC and the toxicities of current multimodality treatment in a young population serve as the impetus to evaluate de-intensification treatment regimens aimed at reducing toxicity while maintaining therapeutic efficacy. Clinical trials are underway to evaluate reduced doses of radiation or less toxic systemic therapy regimens in HPV-OPC. Minimally invasive surgical approaches in the HPV-OPC population with early tumor stage also are being investigated. De-intensification strategies should only be employed in the context of clinical trials, and HPV-OPC patients should be offered clinical trials' participation. Appropriate patient selection is critical to the development of de-intensification regimens, and this requires greater understanding of risk factors within the HPV-OPC population, HPV-OPC biology, and how HPV modulates response to specific therapies. Smoking history and bulky nodal disease have been shown to impact negatively the favorable prognosis of HPV association. Validated biomarkers within the HPV-OPC population are lacking, although alterations in the PI3K pathway and markers of immune response may emerge as important considerations in the future. Novel therapeutic strategies are desperately needed particularly for HPV-OPC patients who fail definitive therapy, and select patients with recurrent or metastatic disease may benefit from aggressive approaches.

Mandibular osteoradionecrosis in squamous cell carcinoma of the oral cavity and oropharynx: incidence and risk factors.

PubMed

Monnier, Yan; Broome, Martin; Betz, Michael; Bouferrache, Kahina; Ozsahin, Mahmut; Jaques, Bertrand

2011-05-01

Mandibular osteoradionecrosis (ORN) is a serious complication of radiotherapy (RT) in head and neck cancer patients. The aim of this study was to analyze the incidence of and risk factors for mandibular ORN in squamous cell carcinoma (SCC) of the oral cavity and oropharynx. Case series with chart review. University tertiary care center for head and neck oncology. Seventy-three patients treated for stage I to IV SCC of the oral cavity and oropharynx between 2000 and 2007, with a minimum follow-up of 2 years, were included in the study. Treatment modalities included both RT with curative intent and adjuvant RT following tumor surgery. The log-rank test and Cox model were used for univariate and multivariate analyses. The incidence of mandibular ORN was 40% at 5 years. Using univariate analysis, the following risk factors were identified: oral cavity tumors (P < .01), bone invasion (P < .02), any surgery prior to RT (P < .04), and bone surgery (P < .0001). By multivariate analysis, mandibular surgery proved to be the most important risk factor and the only one reaching statistical significance (P < .0002). Mandibular ORN is a frequent long-term complication of RT for oral cavity and oropharynx cancers. Mandibular surgery before irradiation is the only independent risk factor. These aspects must be considered when planning treatment for these tumors.

Endocrine correlates of susceptibility to motion sickness

NASA Technical Reports Server (NTRS)

Kohl, R. L.

1985-01-01

Motion sickness releases ACTH, epinerphrine, and norepinephrine. The endocrine responses to motion sickness, adaptive responses leading to the resolution of the syndrome, and the way in which antimotion-sickness drugs influence the endocrine responses were studied. Susceptible or insusceptible subjects were administered antimotion-sickness drugs prior to stressful stimulation. Insusceptible subjects displayed more pronounced elevations of ACTH, epinephrine, and norepinephrine after stressful motion. Predrug levels of ACTH were higher in insusceptible subjects (p less than 0.01). Acute blockade of hormone responses to stressful motion or alteration of levels of ACTH by drugs were not correlated with individual susceptibility. No correlation was apparent between epinephrine and ACTH release. These endocrine differences may represent neurochemical markers for susceptibility to motion, stress, or general adaptability, and it may be that the chronic modulation of their levels might be more effective in preventing motion sickness than the acute blockage or stimulation of specific receptors.

Proton pump inhibitor medication is associated with colonisation of gut flora in the oropharynx.

PubMed

Tranberg, A; Thorarinsdottir, H R; Holmberg, A; Schött, U; Klarin, B

2018-03-08

The normal body exists in mutualistic balance with a large range of microbiota. The primary goal of this study was to establish whether there is an imbalance in the oropharyngeal flora early after hospital or ICU admittance, and whether flora differs between control, ward and critically ill patients. The secondary goal was to explore whether there are patient characteristics that can be associated with a disturbed oropharyngeal flora. Oropharyngeal cultures were obtained from three different study groups: (1) controls from the community, (2) ward patients and (3) critically ill patients, the two latter within 24 h after admittance. Cultures were obtained from 487 individuals: 77 controls, 193 ward patients and 217 critically ill patients. Abnormal pharyngeal flora was more frequent in critically ill and ward patients compared with controls (62.2% and 10.4% vs. 1.3%, P < 0.001 and P = 0.010, respectively). Colonisation of gut flora in the oropharynx was more frequent in critically ill patients compared with ward patients or controls (26.3% vs. 4.7% and 1.3%, P < 0.001 and P < 0.001, respectively). Proton pump inhibitor medication was the strongest independent factor associated with the presence of gut flora in the oropharynx in both ward and critically ill patients (P = 0.030 and P = 0.044, respectively). This study indicates that abnormal oropharyngeal flora is an early and frequent event in hospitalised patients and more so in the critically ill, compared to controls. Proton pump inhibitor medication is associated with colonisation of gut flora in the oropharynx. © 2018 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

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

PubMed Central

Seccia, V.; Cocuzza, P.; Ferrazza, P.; Briganti, T.; Matteucci, F.; Fatigante, L.; Giusti, P.; Grosso, M.; Locantore, L.; Morganti, R.; Nacci, A.; Sellari Franceschini, S.; Paiar, F.; Caramella, D.; Fattori, B.

2016-01-01

SUMMARY The objective of this study is to report the initial results of a prospective trial assessing instrumental deglutition function in nasopharynx and oropharynx cancers after radio or chemoradiotherapy using intensity-modulated radiotherapy (IMRT). IMRT was delivered aiming to spare the swallowing organ at risk (SWOARs) for Stage II-IV naso- and oropharynx cancer. Objective instrumental assessment included videofluoroscopy (VFS), fiberoptic endoscopic evaluation of swallowing (FEES) and oro-pharyngeal-oesophageal scintigraphy (OPES) at baseline and at 1 month after radiotherapy. Dysphagia parameter scores were calculated at each exam after liquid (L) and semi-liquid (SL) bolus intake: pre-deglutition penetration, aspiration, pharyngeal transit time (PTT) and hypopharyngeal retention index (HPRI). Overall, 20 patients (6 nasophaynx and 14 oropharynx) completed treatment and instrumental assessment after 1 month. Comparison between pre- and post-treatment HPRI score values showed a significant worsening in both FEES-L (p = 0.021) and SL (p = 0.02) and at VFS-L (p = 0.008) and SL (p = 0.005). Moreover, a relationship between HPRI worsening at FEES-L and FEES-SL (p = 0.005) as well as at VFS-L and VFS-SL (p < 0.001) was observed. PTT was not significantly affected by radiotherapy (p > 0.2). Only a few patients experienced pre-deglutition penetration (1 patient with base of tongue cancer at FEES-L and SL) and aspiration (1 patient with nasopharynx cancer at OPES-L and FEES-SL) after radiotherapy. Our early results showed that IMRT-SWOARs sparing caused a significant increase in the post-deglutition HPRI score. Longer follow-up will be necessary to evaluate if the increase of HPRI is related to a high risk of developing late aspiration. PMID:27070541

EVALUATION OF TRICLOSAN AS A POTENTIAL ENDOCRINE DISRUPTING CHEMICAL

EPA Science Inventory

Triclosan is an industrial antibacterial agent commonly used in soaps, toothpaste and cleaners. The present investigation was designed to examine the endocrine modulating potential of Triclosan because its chemical structure closely resembles known non-steroidial estrogens (e.g. ...

Endocrine glands

MedlinePlus Videos and Cool Tools

... the pancreas, ovaries and testes. The endocrine and nervous systems work very closely together. The brain continuously sends ... endocrine glands. Because of this intimate relationship, the nervous and endocrine systems are referred to as the neuroendocrine system. The ...

p73 G4C14-to-A4T14 Polymorphism and Risk of Human Papillomavirus Associated Squamous Cell Carcinoma of the Oropharynx in Never Smokers and Never Drinkers

PubMed Central

Chen, Xingming; Sturgis, Erich M.; Etzel, Carol J.; Wei, Qingyi; Li, Guojun

2008-01-01

BACKGROUND p73 can be inactivated by oncoprotein E6 of human papillomavirus (HPV). It is possible that p73 variation could alter the interaction between the E6 protein and p73, and thus alter the risk for HPV associated carcinogenesis. The p73 G4C14-to-A4T14 polymorphism is thought to affect p73 function by altering gene expression, but whether this also alters the risk of HPV16 associated squamous cell carcinoma of the oropharynx (SCCOP) is unknown. METHODS This case-control study included 188 non-Hispanic white patients with newly diagnosed SCCOP and 349 healthy control subjects. Logistic regression analyses were used to calculate odds ratio (OR) and 95% confidence interval (CI) for cases and controls stratified by p73 genotype, age, sex, smoking, drinking and HPV16 status. The effects of p73 genotypes on risk of HPV16 associated SCCOP were explored with further stratification by smoking and drinking status. RESULTS HPV16 seropositivity was associated with an increased risk of SCCOP (adjusted OR, 5.98; 95% CI, 3.89-9.20), especially among never smokers (adjusted OR, 13.8; 95% CI, 5.91-32.1), never drinkers (adjusted OR, 14.9; 95% CI, 5.24-42.4), and subjects with p73 variant genotypes (GC/AT + AT/AT) (adjusted OR, 7.96; 95% CI, 3.83-16.5). Moreover, the risk of HPV16 associated SCCOP for those with p73 variant genotypes was particularly high in never smokers and never drinkers. CONCLUSIONS p73 G4C14-to-A4T14 polymorphism may modulate the risk of HPV16 associated SCCOP and the p73 variant genotypes may be a marker of genetic susceptibility to HPV16 associated SCCOP, particularly in never smokers and never drinkers. Condensed abstract p73 G4C14-to-A4T14 polymorphism may modulate the risk of HPV16 associated squamous cell carcinoma of the oropharynx and the p73 variant genotypes may be a marker of genetic susceptibility to HPV16 associated squamous cell carcinoma of the oropharynx, particularly in never smokers and never drinkers. PMID:18988287

Isohormonal therapy of endocrine autoimmunity.

PubMed

Schloot, N; Eisenbarth, G S

1995-06-01

For most autoimmune disorders, the site (if any) of chronic immunization required for perpetuation of autoimmunity is unknown. However, one possible site is the target organ itself. If this were the case, feedback regulation of target cell activity might influence autoimmunity. Here, Nanette Schloot and George Eisenbarth review several recent studies suggesting that therapies that inhibit hormonal secretion of target endocrine organs, and/or modulate immunity by therapy with the isohormone, are associated with disease suppression.

An overview of estrogen-associated endocrine disruption in fishes: evidence of effects on reproductive and immune physiology

USGS Publications Warehouse

Iwanowicz, L.R.; Blazer, V.S.

2011-01-01

Simply and perhaps intuitively defined, endocrine disruption is the abnormal modulation of normal hormonal physiology by exogenous chemicals. In fish, endocrine disruption of the reproductive system has been observed worldwide in numerous species and is known to affect both males and females. Observations of biologically relevant endocrine disruption most commonly occurs near waste water treatment plant outfalls, pulp and paper mills, and areas of high organic loading sometimes associated with agricultural practices. Estrogenic endocrine disrupting chemicals (EEDCs) have received an overwhelmingly disproportionate amount of scientific attention compared to other EDCs in recent years. In male fishes, exposure to EEDCs can lead to the induction of testicular oocytes (intersex), measurable plasma vitellogenin protein, altered sex steroid profiles, abnormal spawning behavior, skewed population sex ratios, and lessened reproductive success. Interestingly, contemporary research purports that EDCs modulate aspects of non-reproductive physiology including immune function. Here we present an overview of endocrine disruption in fishes associated with estrogenic compounds, implications of this phenomenon, and examples of EDC related research findings by our group in the Potomac River Watershed, USA.

Comparative assessment of endocrine modulators with oestrogenic activity: I. Definition of a hygiene-based margin of safety (HBMOS) for xeno-oestrogens against the background of European developments.

PubMed

Bolt, H M; Janning, P; Michna, H; Degen, G H

2001-01-01

A novel concept - the hygiene-based margin of safety (HBMOS) - is suggested for the assessment of the impact of potential endocrine modulators. It integrates exposure scenarios and potency data for industrial chemicals and naturally occurring dietary compounds with oestrogenic activity. An HBMOS is defined as a quotient of estimated daily intakes weighted by the relative in vivo potencies of these compounds. The Existing Chemicals Programme of the European Union provides Human and Environmental Risk Assessments of Existing Chemicals which include human exposure scenarios. Such exposure scenarios, along with potency estimates for endocrine activities, may provide a basis for a quantitative comparison of the potential endocrine-modulating effects of industrial chemicals with endocrine modulators as natural constituents of human diet. Natural phyto-oestrogens exhibit oestrogenic activity in vitro and in vivo. Important phyto-oestrogens for humans are isoflavones (daidzein, genistein) and lignans, with the highest quantities found in soybeans and flaxseed, respectively. Daily isoflavone exposures calculated for infants on soy-based formulae were in the ranges of 4.5-8 mg/kg body wt.; estimates for adults range up to 1 mg/kg body wt. The Senate Commission on the Evaluation of Food Safety (SKLM) of the Deutsche Forschungsgemeinschaft has also indicated a wide range of dietary exposures. For matters of risk assessment, the SKLM has based recommendations on dietary exposure scenarios, implying a daily intake of phyto-oestrogens in the order of 1 mg/kg body wt. On the basis of information compiled within the Existing Chemicals Programme of the EU, it appears that a daily human exposure to nonylphenol of 2 microg/kg body wt. may be a worst-case assumption, but which is based on valid scenarios. The intake of octylphenol is much lower, due to a different use pattern and applications, and may be neglected. Data from migration studies led to estimations of the daily human

AUTONOMIC AXONS IN THE HUMAN ENDOCRINE PANCREAS SHOW UNIQUE INNERVATION PATTERNS

PubMed Central

Rodriguez-Diaz, Rayner; Abdulreda, Midhat H.; Formoso, Alexander L.; Gans, Itai; Ricordi, Camillo; Berggren, Per-Olof; Caicedo, Alejandro

2011-01-01

SUMMARY The autonomic nervous system regulates hormone secretion from the endocrine pancreas, the islets of Langerhans, and thus impacts glucose metabolism. The parasympathetic and sympathetic nerves innervate the pancreatic islet, but the precise innervation patterns are not known, particularly in human islets. Here we demonstrate that the innervation of human islets is different from that of mouse islets and that it does not conform to existing models of autonomic control of islet function. By visualizing axons in three dimensions and quantifying axonal densities and contacts within pancreatic islets, we found that, in contrast to mouse endocrine cells, human endocrine cells are sparsely contacted by autonomic axons. Few parasympathetic cholinergic axons penetrate the human islet and the invading sympathetic fibers preferentially innervate smooth muscle cells of blood vessels located within the islet. Thus, rather than modulating endocrine cell function directly, sympathetic nerves may regulate hormone secretion in human islets by controlling local blood flow or by acting on islet regions located downstream. PMID:21723503

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

Laron syndrome abnormalities: spinal stenosis, os odontoideum, degenerative changes of the atlanto-odontoid joint, and small oropharynx.

PubMed

Kornreich, Liora; Horev, Gadi; Schwarz, Michael; Karmazyn, Boaz; Laron, Zvi

2002-04-01

Patients with Laron syndrome have an inborn growth hormone resistance. We investigated abnormalities in the upper airways and cervical spine in patients with Laron syndrome. We prospectively examined 11 patients (one child aged 9 years and 10 adults aged 36-68 years), 10 of whom underwent MR imaging of the spine or head; nine, radiography of the cervical spine; and four, CT of C1-C2. The width of the spinal canal was evaluated visually and quantitatively and compared with reference values. The smallest diameter of the oropharynx and the thickness of the palate were measured and compared with reference values. Nine age-matched female patients referred for MR imaging for unrelated reasons served as control subjects. Cervical spinal stenosis was present in seven of the adult patients, within a confidence interval of 95%. Anomaly of the dens compatible with os odontoideum was present in three patients, causing focal myelomalacia in two. The atlanto-odontoid joint showed osteoarthritic changes in six of the adult patients. The mediolateral diameter of the oropharynx was significantly smaller in the patients with Laron syndrome than in the control subjects (P <.005). There was no difference in the thickness of the soft palate. Patients with Laron syndrome develop significant narrowing of the cervical spinal canal and early degenerative changes of the atlanto-odontoid joint. Laron syndrome is associated with os odontoideum causing myelomalacia. The dimensions of the oropharynx are small. Patients may be prone to neurologic morbidity and sleep disturbances. Routine MR imaging of the cervical spine is recommended in these patients.

EVALUATION OF TRICLOSAN AS A POTENTIAL ENDOCRINE DISRUPTING CHEMICAL (POSTER SESSION)

EPA Science Inventory

Triclosan is an industrial antibacterial agent commonly used in soaps, toothpaste and cleaners. The present investigation was designed to examine the endocrine modulating potential of Triclosan because its chemical structure closely resembles known non-steroidial estrogens (e.g. ...

Physiology of the endocrine pancreas.

PubMed

Engelking, L R

1997-11-01

The endocrine pancreas is composed of nests of cells called the islets of Langerhans, which comprise only about 20% of pancreatic cell mass and secrete insulin, glucagon, somatostatin, and pancreatic polypeptide. Insulin is anabolic, increasing storage of glucose, fatty acids and amino acids, while glucagon namely stimulates hepatic glycogenolysis, gluconeogenesis, and ketogenesis. Somatostatin acts as a paracrine agent to inhibit both insulin and glucagon release, and, therefore, to modulate their output. This article explores factors controlling release of these hormones, as well as the way in which they affect fuel metabolism in the whole animal.

Retrospective analysis of insulin responses to standard dosed oral glucose tests (OGTs) via naso-gastric tubing towards definition of an objective cut-off value.

PubMed

Warnken, Tobias; Delarocque, Julien; Schumacher, Svenja; Huber, Korinna; Feige, Karsten

2018-01-19

Insulin dysregulation (ID) with basal or postprandial hyperinsulinemia is one of the key findings in horses and ponies suffering from the equine metabolic syndrome (EMS). Assessment of ID can easily be performed in clinical settings by the use of oral glucose challenge tests. Oral glucose test (OGT) performed with 1 g/kg bodyweight (BW) glucose administered via naso-gastric tube allows the exact administration of a defined glucose dosage in a short time. However, reliable cut-off values have not been available so far. Therefore, the aim of the study was to describe variations in insulin response to OGT via naso-gastric tubing and to provide a clinical useful cut-off value for ID when using the insulin quantification performed with an equine-optimized insulin enzyme-linked immunosorbent assay. Data visualization revealed no clear separation in the serum insulin concentration of insulin sensitive and insulin dysregulated horses during OGT. Therefore, a model based clustering method was used to circumvent the use of an arbitrary limit for categorization. This method considered all data-points for the classification, taking into account the individual insulin trajectory during the OGT. With this method two clusters were differentiated, one with low and one with high insulin responses during OGT. The cluster of individuals with low insulin response was consistently detected, independently of the initialization parameters of the algorithm. In this cluster the 97.5% quantile of insulin is 110 µLU/mL at 120 min. We suggest using this insulin concentration of 110 µLU/mL as a cut-off value for samples obtained at 120 min in OGT. OGT performed with 1 g/kg BW glucose and administration via naso-gastric tubing can easily be performed under clinical settings. Application of the cut-off value of 110 µLU/mL at 120 min allows assessment of ID in horses.

Endocrine responses to acute and chronic high-altitude exposure (4,300 meters): modulating effects of caloric restriction.

PubMed

Barnholt, Kimberly E; Hoffman, Andrew R; Rock, Paul B; Muza, Stephen R; Fulco, Charles S; Braun, Barry; Holloway, Leah; Mazzeo, Robert S; Cymerman, Allen; Friedlander, Anne L

2006-06-01

High-altitude anorexia leads to a hormonal response pattern modulated by both hypoxia and caloric restriction (CR). The purpose of this study was to compare altitude-induced neuroendocrine changes with or without energy imbalance and to explore how energy sufficiency alters the endocrine acclimatization process. Twenty-six normal-weight, young men were studied for 3 wk. One group [hypocaloric group (HYPO), n = 9] stayed at sea level and consumed 40% fewer calories than required to maintain body weight. Two other groups were deployed to 4,300 meters (Pikes Peak, CO), where one group (ADQ, n = 7) was adequately fed to maintain body weight and the other [deficient group (DEF), n = 10] had calories restricted as above. HYPO experienced a typical CR-induced reduction in many hormones such as insulin, testosterone, and leptin. At altitude, fasting glucose, insulin, and epinephrine exhibited a muted rise in DEF compared with ADQ. Free thyroxine, thyroid-stimulating hormone, and norepinephrine showed similar patterns between the two altitude groups. Morning cortisol initially rose higher in DEF than ADQ at 4,300 meters, but the difference disappeared by day 5. Testosterone increased in both altitude groups acutely but declined over time in DEF only. Adiponectin and leptin did not change significantly from sea level baseline values in either altitude group regardless of energy intake. These data suggest that hypoxia tends to increase blood hormone concentrations, but anorexia suppresses elements of the endocrine response. Such suppression results in the preservation of energy stores but may sacrifice the facilitation of oxygen delivery and the use of oxygen-efficient fuels.

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

Dynamics of genomic H3K27me3 domains and role of EZH2 during pancreatic endocrine specification

PubMed Central

Xu, Cheng-Ran; Li, Lin-Chen; Donahue, Greg; Ying, Lei; Zhang, Yu-Wei; Gadue, Paul; Zaret, Kenneth S

2014-01-01

Endoderm cells undergo sequential fate choices to generate insulin-secreting beta cells. Ezh2 of the PRC2 complex, which generates H3K27me3, modulates the transition from endoderm to pancreas progenitors, but the role of Ezh2 and H3K27me3 in the next transition to endocrine progenitors is unknown. We isolated endoderm cells, pancreas progenitors, and endocrine progenitors from different staged mouse embryos and analyzed H3K27me3 genome-wide. Unlike the decline in H3K27me3 domains reported during embryonic stem cell differentiation in vitro, we find that H3K27me3 domains increase in number during endocrine progenitor development in vivo. Genes that lose the H3K27me3 mark typically encode transcriptional regulators, including those for pro-endocrine fates, whereas genes that acquire the mark typically are involved in cell biology and morphogenesis. Deletion of Ezh2 at the pancreas progenitor stage enhanced the production of endocrine progenitors and beta cells. Inhibition of EZH2 in embryonic pancreas explants and in human embryonic stem cell cultures increased endocrine progenitors in vitro. Our studies reveal distinct dynamics in H3K27me3 targets in vivo and a means to modulate beta cell development from stem cells. PMID:25107471

Parathyroid Hormone-Related Peptide: A Novel Endocrine Cardioprotective "Conditioning Mimetic".

PubMed

Datta, Tanuka; Przyklenk, Karin; Datta, Nabanita S

2017-11-01

An as-yet limited body of evidence suggests that calcium-regulating endocrine hormones-in particular, parathyroid hormone-related peptide (PTHrP)-may have unappreciated cardioprotective effects. The current review focuses on the concept that PTHrP may, via modulation of classic cardioprotective signaling pathways, provide a novel strategy to attenuate myocardial ischemia-reperfusion injury.

Identification and assessment of endocrine disruptors: limitations of in vivo and in vitro assays.

PubMed Central

Zacharewski, T

1998-01-01

It has been suggested that chemicals and complex mixtures capable of modulating the endocrine system may contribute to adverse health, reproduction, and developmental effects in humans and wildlife. These effects include increased incidence of hormone-dependent cancers, compromised reproductive fitness, and abnormal reproductive system development. In response to public concern, regulatory agencies in North America and Europe are formulating potential strategies to systematically test chemicals and complex mixtures for their endocrine-disrupting activities. Because of the complexity of the endocrine system and the number of potential endocrine disruptor targets, a tiered approach involving a complementary battery of short- and long-term in vivo and in vitro assays that assesses both receptor and nonreceptor-mediated mechanisms of action is being considered. However, the available established assays use a limited number of end points, and significant information gaps exist for other potential targets in the endocrine system. In addition to discussing the merits and limitations of the assays that may be adopted, this paper also highlights potential problems associated with the use of a tiered testing strategy. PMID:9599705

Modulation of cytokine expression in human macrophages by endocrine-disrupting chemical Bisphenol-A

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Yanzhen; Mei, Chenfang; Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Institute of Microbiology, Guangzhou 510070

Highlights: • Effects of BPA on the cytokines expression of human macrophages were investigated. • BPA increased pro-inflammation cytokines TNF-α and IL-6 production. • BPA decreased anti-inflammation IL-10 and TGF-β production. • ERα/β/ERK/NF-κB signaling involved in BPA-mediated cytokines expression. - Abstract: Exposure to environmental endocrine-disrupting chemical Bisphenol-A (BPA) is often associated with dysregulated immune homeostasis, but the mechanisms remain unclear. In the present study, the effects of BPA on the cytokines responses of human macrophages were investigated. Treatment with BPA increased pro-inflammation cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production, but decreased anti-inflammation cytokines interleukin-10 (IL-10) and transforming growthmore » factor-β (TGF-β) production in THP1 macrophages, as well as in primary human macrophages. BPA effected cytokines expression through estrogen receptor α/β (ERα/β)-dependent mechanism with the evidence of ERα/β antagonist reversed the expression of cytokines. We also identified that activation of extracellular regulated protein kinases (ERK)/nuclear factor κB (NF-κB) signal cascade marked the effects of BPA on cytokines expression. Our results indicated that BPA effected inflammatory responses of macrophages via modulating of cytokines expression, and provided a new insight into the link between exposure to BPA and human health.« less

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

USGS Publications Warehouse

Writer, J.H.; Barber, L.B.; Brown, G.K.; Taylor, Howard 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.

Smartphone-coupled rhinolaryngoscopy at the point of care

NASA Astrophysics Data System (ADS)

Mink, Jonah; Bolton, Frank J.; Sebag, Cathy M.; Peterson, Curtis W.; Assia, Shai; Levitz, David

2018-02-01

Rhinolaryngoscopy remains difficult to perform in resource-limited settings due to the high cost of purchasing and maintaining equipment as well as the need for specialists to interpret exam findings. While the lack of expertise can be obviated by adopting telemedicine-based approaches, the capture, storage, and sharing of images/video is not a common native functionality of medical devices. Most rhinolaryngoscopy systems consist of an endoscope that interfaces with the patient's naso/oropharynx, and a tower of modules that record video/images. However, these expensive and bulky modules can be replaced by a smartphone that can fulfill the same functions but at a lower cost. To demonstrate this, a commercially available rhinolaryngoscope was coupled to a smartphone using a 3D-printed adapter. Software developed for other clinical applications was repurposed for ENT use, including an application that controls image and video capture, a HIPAA-compliant image/video storage and transfer cloud database, and customized software features developed to improve practitioner competency. Audio recording capabilities to assess speech pathology were also integrated into the smartphone rhinolaryngoscope system. The illumination module coupled onto the endoscope remained unchanged. The spatial resolution of the rhinolaryngoscope system was defined by the fiber diameter of endoscope fiber bundle, rather than the smartphone camera. The mobile rhinolaryngoscope system was used with appropriate patients by a general practitioner in an office setting. The general practitioner then consulted with an ENT specialist via the HIPAA compliant cloud database and workflow modules on difficult cases. These results suggest the smartphone-based rhinolaryngoscope holds promise for use in low-resource settings.

NasoNet, modeling the spread of nasopharyngeal cancer with networks of probabilistic events in discrete time.

PubMed

Galán, S F; Aguado, F; Díez, F J; Mira, J

2002-07-01

The spread of cancer is a non-deterministic dynamic process. As a consequence, the design of an assistant system for the diagnosis and prognosis of the extent of a cancer should be based on a representation method that deals with both uncertainty and time. The ultimate goal is to know the stage of development of a cancer in a patient before selecting the appropriate treatment. A network of probabilistic events in discrete time (NPEDT) is a type of Bayesian network for temporal reasoning that models the causal mechanisms associated with the time evolution of a process. This paper describes NasoNet, a system that applies NPEDTs to the diagnosis and prognosis of nasopharyngeal cancer. We have made use of temporal noisy gates to model the dynamic causal interactions that take place in the domain. The methodology we describe is general enough to be applied to any other type of cancer.

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.

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

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.

ENDOCRINE DISRUPTORS IN THE ENVIRONMENT

EPA Science Inventory

The endocrine system produces hormones which are powerful natural chemicals that regulate important life processes. Endocrine disruptors are human-made chemicals distributed globally which have the potential to interfere with the endocrine system and produce serious biological e...

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. Copyright © 2016 Elsevier Inc. All rights reserved.

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. Copyright © 2015 Elsevier Inc. All rights reserved.

Endocrine-related adverse events associated with immune checkpoint blockade and expert insights on their management.

PubMed

Sznol, Mario; Postow, Michael A; Davies, Marianne J; Pavlick, Anna C; Plimack, Elizabeth R; Shaheen, Montaser; Veloski, Colleen; Robert, Caroline

2017-07-01

Agents that modulate immune checkpoint proteins, such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death receptor-1 (PD-1), have become a mainstay in cancer treatment. The clinical benefit afforded by immune checkpoint inhibitors can be accompanied by immune-related adverse events (irAE) that affect the skin, gastrointestinal tract, liver, and endocrine system. The types of irAEs associated with immune checkpoint inhibitors are generally consistent across tumor types. Immune-related endocrine events can affect the pituitary, thyroid, and adrenal glands, as well as other downstream target organs. These events are unique when compared with other irAEs because the manifestations are often irreversible. Immune-related endocrine events are typically grade 1/2 in severity and often present with non-specific symptoms, making them difficult to diagnose. The mechanisms underlying immune-related target organ damage in select individuals remain mostly undefined. Management includes close patient monitoring, appropriate laboratory testing for endocrine function, replacement of hormones, and consultation with an endocrinologist when appropriate. An awareness of the symptoms and management of immune-related endocrine events may aid in the safe and appropriate use of immune checkpoint inhibitors in clinical practice. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

[The immuno-endocrine system. A new endocrine theory: the problem of the packed transport].

PubMed

Csaba, György

2011-05-15

Since the eighties of the last century hormone content was justified in immune cells (lymphocytes, granulocytes, monocytes, macrophages and mast cells), which produce, store and secrete these hormones. Although the amount of these materials in immune cells is relatively small, the mass of the producers (immune cells) is so large, that the phenomenon must be considered from endocrinological point of view, underlying the important differences between the "classical" and immuno-endocrine systems. Cells of the classic (built-in) endocrine system are mono-producers, while immune cells can synthesize many types of hormones (polyproducers). In addition, these cells can transport the whole hormone-producing machinery to the site of need, producing a local effect. This can be observed, for example, in the case of endorphin producing immune cells during inflammation and during early pregnancy around the chorionic villi. Hormone producing immune cells also have receptors for many hormones, so that they are poly-receivers. Via hormone producing and receiving capacity there is a bidirectional connection between the neuro-endocrine and immuno-endocrine systems. In addition, there is a network inside the immuno-endocrine system. The packed transport theory attempts to explain the mechanism and importance of the immuno-endocrine system.

Endocrine and other physiologic modulators of perinatal cardiomyocyte endowment

PubMed Central

Jonker, S S; Louey, S

2015-01-01

Immature contractile cardiomyocytes proliferate to rapidly increase cell number, establishing cardiomyocyte endowment in the perinatal period. Developmental changes in cellular maturation, size and attrition further contribute to cardiac anatomy. These physiological processes occur concomitant with a changing hormonal environment as the fetus prepares itself for the transition to extrauterine life. There are complex interactions between endocrine, hemodynamic and nutritional regulators of cardiac development. Birth has been long assumed to be the trigger for major differences between the fetal and postnatal cardiomyocyte growth patterns, but investigations in normally growing sheep and rodents suggest this may not be entirely true; in sheep, these differences are initiated before birth, while in rodents they occur after birth. The aim of this review is to draw together our understanding of the temporal regulation of these signals and cardiomyocyte responses relative to birth. Further, we consider how these dynamics are altered in stressed and suboptimal intrauterine environments. PMID:26432905

Bisphenol A (BPA) modulates the expression of endocrine and stress response genes in the freshwater snail Physa acuta.

PubMed

Morales, Mónica; Martínez-Paz, Pedro; Sánchez-Argüello, Paloma; Morcillo, Gloria; Martínez-Guitarte, José Luis

2018-05-15

Bisphenol A (BPA), a known endocrine disrupting chemical (EDC) that can mimic the action of oestrogens by interacting with hormone receptors, is potentially able to influence reproductive functions in vertebrates and invertebrates. The freshwater pulmonate Physa acuta is a sensitive organism to xenobiotics appropriate for aquatic toxicity testing in environmental studies. This study was conducted to explore the effects of BPA on the Gastropoda endocrine system. The effects following a range of exposure times (5-96h) to BPA in P. acuta were evaluated at the molecular level by analysing changes in the transcriptional activity of the endocrine-related genes oestrogen receptor (ER), oestrogen-related receptor (ERR), and retinoid X receptor (RXR), as well as in genes involved in the stress response, such as hsp70 and hsp90. Real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis showed that BPA induced a significant increase in the mRNA levels of ER, ERR, and RXR, suggesting that these receptors could be involved in similar pathways or regulation events in the endocrine disruptor activity of this chemical at the molecular level in Gastropoda. Additionally, the hsp70 expression was upregulated after 5 and 72h of BPA exposures, but hsp90 was only upregulated after 5h of BPA exposure. Finally, we assessed the glutathione-S-transferase (GST) activity after BPA treatment and found that it was affected after 48h. In conclusion, these data provide, for the first time, evidences of molecular effects produced by BPA in the endocrine system of Gastropoda, supporting the potential of ER, ERR and RXR as biomarkers to analyse putative EDCs in ecotoxicological studies. Moreover, our results suggest that P. acuta is an appropriate sentinel organism to evaluate the effect of EDCs in the freshwater environment. Copyright © 2018 Elsevier Inc. All rights reserved.

Hormones and immunity in cancer: are thyroid hormones endocrine players in the microglia/glioma cross-talk?

PubMed Central

Perrotta, Cristiana; De Palma, Clara; Clementi, Emilio; Cervia, Davide

2015-01-01

Accumulating evidence indicates that the endocrine and immune systems engage in complex cross-talks in which a prominent role is played by thyroid hormones (THs). The increase of resident vs. monocyte recruited macrophages was shown to be an important effector of the TH 3,3′,5′-Triiodo-L-thyronine (T3)-induced protection against inflammation and a key role of T3 in inhibiting the differentiation of peripheral monocytes into macrophages was observed. Herein, we report on the role of T3 as a modulator of microglia, the specialized macrophages of the central nervous system (CNS). Mounting evidence supports a role of microglia and macrophages in the growth and invasion of malignant glioma. In this respect, we unveil the putative involvement of T3 in the microglia/glioma cell communication. Since THs are known to cross the blood-brain barrier, we suggest that T3 not only exerts a direct modulation of brain cancer cell itself but also indirectly promotes glioma growth through a modulation of microglia. Our observations expand available information on the role of TH system in glioma and its microenvironment and highlight the endocrine modulation of microglia as an important target for future therapeutic development of glioma treatments. PMID:26157361

Redox-mediated enrichment of self-renewing adult human pancreatic cells that possess endocrine differentiation potential.

PubMed

Linning, Katrina D; Tai, Mei-Hui; Madhukar, Burra V; Chang, C C; Reed, Donald N; Ferber, Sarah; Trosko, James E; Olson, L Karl

2004-10-01

The limited availability of transplantable human islets has stimulated the development of methods needed to isolate adult pancreatic stem/progenitor cells capable of self-renewal and endocrine differentiation. The objective of this study was to determine whether modulation of intracellular redox state with N-acetyl-L-cysteine (NAC) would allow for the propagation of pancreatic stem/progenitor cells from adult human pancreatic tissue. Cells were propagated from human pancreatic tissue using a serum-free, low-calcium medium supplemented with NAC and tested for their ability to differentiate when cultured under different growth conditions. Human pancreatic cell (HPC) cultures coexpressed alpha-amylase, albumin, vimentin, and nestin. The HPC cultures, however, did not express other genes associated with differentiated pancreatic exocrine, duct, or endocrine cells. A number of transcription factors involved in endocrine cell development including Beta 2, Islet-1, Nkx6.1, Pax4, and Pax6 were expressed at variable levels in HPC cultures. In contrast, pancreatic duodenal homeobox factor 1 (Pdx-1) expression was extremely low and at times undetectable. Overexpression of Pdx-1 in HPC cultures stimulated somatostatin, glucagon, and carbonic anhydrase expression but had no effect on insulin gene expression. HPC cultures could form 3-dimensional islet-like cell aggregates, and this was associated with expression of somatostatin and glucagon but not insulin. Cultivation of HPCs in a differentiation medium supplemented with nicotinamide, exendin-4, and/or LY294002, an inhibitor of phosphatidylinositol-3 kinase, stimulated expression of insulin mRNA and protein. These data support the use of intracellular redox modulation for the enrichment of pancreatic stem/progenitor cells capable of self-renewal and endocrine differentiation.

[Arterial hypertension secondary to endocrine disorders].

PubMed

Minder, Anna; Zulewski, Henryk

2015-06-01

Endocrine hypertension offers a potentially curative therapy if the underlying cause is identified and treated accordingly. In contrast to the high prevalence of arterial hypertension especially in the elderly, the classical endocrine causes remain a rare entity. Among patients with arterial hypertension the prevalence of Cushing's syndrome or pheochromocytoma is less than 1%. Primary hyperaldosteronism is more frequent with a reported prevalence of up to 9%. In order to avoid unnecessary, costly and potentially harmful evaluations and therapies due to the limited sensitivity and specificity of the critical endocrine tests it is mandatory to limit the exploration for endocrine causes to preselected patients with high pretest probability for an endocrine disorder. Younger age at manifestation of arterial hypertension or drug resistant hypertension together with other clinical signs of an endocrine disorder should raise the suspicion and prompt the appropriate evaluation.

Once and for all, LXRα and LXRβ are gatekeepers of the endocrine system.

PubMed

Maqdasy, Salwan; Trousson, Amalia; Tauveron, Igor; Volle, David H; Baron, Silvère; Lobaccaro, Jean-Marc A

2016-06-01

Liver X receptors (LXRs) α and β are nuclear receptors whose transcriptional activity is regulated by oxysterols, the oxidized forms of cholesterol. Described in the late 1990s as lipid sensors, both LXRs regulate cholesterol and fatty acid homeostasis. Over the years, deep phenotypic analyses of mouse models deficient for LXRα and/or LXRβ have pointed out various other physiological functions including glucose homeostasis, immunology, and neuroprotection. This review enlightens the "endocrine" functions of LXRs; they deeply impact plasma glucose directly and by modulating insulin signaling, renin-angiotensin-aldosterone axis, thyroid and pituitary hormone levels, and bone homeostasis. Besides, LXR signaling is also involved in adrenal physiology, steroid synthesis, and male and female reproduction. Hence, LXRs are definitely involved in the endocrine system and could thus be considered as endocrine receptors, even though oxysterols do not fully correspond to the definition of hormones. Finally, because they are ligand-regulated transcription factors, LXRs are potential pharmacological targets with promising beneficial metabolic effects. Copyright © 2016 Elsevier Ltd. All rights reserved.

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. Copyright © 2010. Published by Elsevier Inc.

Convergent genetic modulation of the endocrine stress response involves polymorphic variations of 5-HTT, COMT and MAOA.

PubMed

Jabbi, M; Korf, J; Kema, I P; Hartman, C; van der Pompe, G; Minderaa, R B; Ormel, J; den Boer, J A

2007-05-01

Highly prevalent stress-related disorders such as major depression (MD) are characterised by a dysregulation of the neuroendocrine system. Although heritability for these disorders is high, the role of genes in the underlying pathophysiology is poorly understood. Here, we show that polymorphic variations in genes coding for serotonin transporter (5-HTT), catechol-O-methyl transferase (COMT) and monoamine oxidase A (MAOA) as well as sex differences influence the regulation of hypothalamic-pituitary-adrenal (HPA)-axis response to acute psychological and endocrine challenges. In our sample, the effects of COMT on the release of adrenocorticotrophin hormone (ACTH) depend on the presence of the low-expression MAOA variant in the same individual. By including individuals varying in their degree of susceptibility to MD, we showed evidence of interactions between 5-HTT and MD susceptibility in baseline cortisol, and between MAOA and MD susceptibility in baseline ACTH measures, indicating a role for these genotypes in stable-state endocrine regulation. Collectively, these results indicate that the simultaneous investigation of multiple monoaminergic genes in interaction with gender have to be measured to understand the endocrine regulation of stress. These findings point towards a genetic susceptibility to stress-related disorders.

Spectrum of Endocrine Disorders in Central Ghana

PubMed Central

Sarfo, Fred Stephen; Ansah, Eunice Oparebea; Kyei, Ishmael

2017-01-01

Background. Although an increasing burden of endocrine disorders is recorded worldwide, the greatest increase is occurring in developing countries. However, the spectrum of these disorders is not well described in most developing countries. Objective. The objective of this study was to profile the frequency of endocrine disorders and their basic demographic characteristics in an endocrine outpatient clinic in Kumasi, central Ghana. Methods. A retrospective review was conducted on endocrine disorders seen over a five-year period between January 2011 and December 2015 at the outpatient endocrine clinic of Komfo Anokye Teaching Hospital. All medical records of patients seen at the endocrine clinic were reviewed by endocrinologists and all endocrinological diagnoses were classified according to ICD-10. Results. 3070 adults enrolled for care in the endocrine outpatient service between 2011 and 2015. This comprised 2056 females and 1014 males (female : male ratio of 2.0 : 1.0) with an overall median age of 54 (IQR, 41–64) years. The commonest primary endocrine disorders seen were diabetes, thyroid, and adrenal disorders at frequencies of 79.1%, 13.1%, and 2.2%, respectively. Conclusions. Type 2 diabetes and thyroid disorders represent by far the two commonest disorders seen at the endocrine clinic. The increased frequency and wide spectrum of endocrine disorders suggest the need for well-trained endocrinologists to improve the health of the population. PMID:28326101

Osteoporosis in celiac disease and in endocrine and reproductive disorders

PubMed Central

Stazi, Anna Velia; Trecca, Antonello; Trinti, Biagino

2008-01-01

As the increase in lifespan brings to light diseases that were previously not clinically detectable, osteoporosis has become an issue of worldwide significance. The disease is marked by a loss of bone mass; the bones become less dense, fragile and more prone to fracturing. Because it is regulated by endocrine and environmental factors, osteoporosis presents a multifactorial etiopathogenesis, with the genetic component accounting for 70% of an individual variation in bone mass density (BMD), the principal determinant, with age, of fracture risk. Pathological conditions such as celiac disease (CD) exacerbate the process of bone loss, so that the occurrence of osteoporosis in celiac subjects is of particular note: indeed, the screening of osteoporosis patients for this disease is advisable, since it may be the only sign of undiagnosed CD. An increase in interleukin IL-1β, of the IL-1 system, in the relatives of celiac patients confirms the genetic predisposition to osteoporosis and its presence is evidence of an association between the two conditions. The direct effect on the bones of CD is secondary to poor absorption of calcium and vitamin D. In women osteoporosis is indirectly associated with early menopause and amenorrhea, and it may follow prolonged breast-feeding and frequent pregnancies, while in men it is associated with hypogonadism and GH deficit. These endocrine and non-endocrine factors exert their effects on bones by modulating the RANK/RANK-L/OPG system. An appropriate lifestyle from adolescence onwards, together with early diagnosis of and treatment for CD and primary and secondary endocrine pathologies are important for the prevention of damage to the bones. PMID:18203279

Endocrine Disruptor Screening Program Reports to Congress

EPA Pesticide Factsheets

This page includes EPA reports to congress on pesticide licensing and endocrine disruptor screening activities, Endocrine Disruptor Methods Validation Subcomittee (EDMVS) progress, and Endocrine Disruptor Screening Program (EDSP) implementation progress.

Analyzing endocrine system conservation and evolution.

PubMed

Bonett, Ronald M

2016-08-01

Analyzing variation in rates of evolution can provide important insights into the factors that constrain trait evolution, as well as those that promote diversification. Metazoan endocrine systems exhibit apparent variation in evolutionary rates of their constituent components at multiple levels, yet relatively few studies have quantified these patterns and analyzed them in a phylogenetic context. This may be in part due to historical and current data limitations for many endocrine components and taxonomic groups. However, recent technological advancements such as high-throughput sequencing provide the opportunity to collect large-scale comparative data sets for even non-model species. Such ventures will produce a fertile data landscape for evolutionary analyses of nucleic acid and amino acid based endocrine components. Here I summarize evolutionary rate analyses that can be applied to categorical and continuous endocrine traits, and also those for nucleic acid and protein-based components. I emphasize analyses that could be used to test whether other variables (e.g., ecology, ontogenetic timing of expression, etc.) are related to patterns of rate variation and endocrine component diversification. The application of phylogenetic-based rate analyses to comparative endocrine data will greatly enhance our understanding of the factors that have shaped endocrine system evolution. Copyright © 2016 Elsevier Inc. All rights reserved.

Endocrine therapy for breast cancer prevention in high-risk women: clinical and economic considerations.

PubMed

Groom, Amy G; Younis, Tallal

2016-01-01

The global burden of breast cancer highlights the need for primary prevention strategies that demonstrate both favorable clinical benefit/risk profile and good value for money. Endocrine therapy with selective estrogen-receptor modulators (SERMs) or aromatase inhibitors (AIs) has been associated with a favorable clinical benefit/risk profile in the prevention of breast cancer in women at high risk of developing the disease. The available endocrine therapy strategies differ in terms of their relative reductions of breast cancer risk, potential side effects, and upfront drug acquisition costs, among others. This review highlights the clinical trials of SERMs and AIs for the primary prevention of breast cancer, and the cost-effectiveness /cost-utility studies that have examined their "value for money" in various health care jurisdictions.

Environmental epigenetics: a role in endocrine disease?

PubMed

Fleisch, Abby F; Wright, Robert O; Baccarelli, Andrea A

2012-10-01

Endocrine disrupting chemicals that are structurally similar to steroid or amine hormones have the potential to mimic endocrine endpoints at the receptor level. However, more recently, epigenetic-induced alteration in gene expression has emerged as an alternative way in which environmental compounds may exert endocrine effects. We review concepts related to environmental epigenetics and relevance for endocrinology through three broad examples: 1) effect of early-life nutritional exposures on future obesity and insulin resistance, 2) effect of lifetime environmental exposures such as ionizing radiation on endocrine cancer risk, and 3) potential for compounds previously classified as endocrine disrupting to additionally or alternatively exert effects through epigenetic mechanisms. The field of environmental epigenetics is still nascent, and additional studies are needed to confirm and reinforce data derived from animal models and preliminary human studies. Current evidence suggests that environmental exposures may significantly impact expression of endocrine-related genes and thereby affect clinical endocrine outcomes.

Polychlorinated biphenyls, mercury, and potential endocrine disruption in fish from the Hudson River, New York, USA

USGS Publications Warehouse

Baldigo, Barry P.; Sloan, R.J.; Smith, S.B.; Denslow, N.D.; Blazer, V.S.; Gross, T.S.

2006-01-01

Tissue residues of total mercury (Hg), total polychlorinated biphenyls (PCBs), and lipid-based PCBs; plasma concentrations of endocrine biomarkers; and reproductive and histologic biomarkers were assessed in 460 carp (Cyprinus carpio), bass (Micropterus salmoides and Micropterus dolomieui), and bullhead (Ameiurus nebulosus) collected from eight sites across the Hudson River Basin in the spring of 1998 to determine if endocrine disruption was evident in resident fish species and to evaluate contaminant-biomarker interrelations. Total PCBs in bed sediments (maximum 2,500 ??g kg-1) could explain 64 to 90% of the variability in lipid-based PCB residues in tissues (maximum 1,250 ??g PCB g-lipid-1) of the four species. The 17??-estradiol to 11-ketotestosterone ratio, typically less than 1.0 in male fish and greater than 1.0 in females, exceeded 1.4 in all male largemouth bass and 35% of male carp and bullhead at one site 21 km downstream from a major PCB source. Endocrine biomarkers were significantly correlated with total Hg in female smallmouth bass and carp, and with lipid-based PCBs in males of all four species. Empirical evidence of endocrine modulation in blood plasma of male and female fish from sites with and without high PCB residues in bed sediments and fish tissues suggest that PCBs, Hg, or other contaminants may disrupt normal endocrine function in fish of the Hudson River. ?? Eawag, 2006.

NASH in Nondiabetic Endocrine Disorders.

PubMed

Wang, Timothy; Yang, Wei; Karakas, Sidika; Sarkar, Souvik

2018-06-06

Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of disease, including hepatic steatosis, inflammation, and fibrosis. NAFLD carries the risk of progression to cirrhosis with its associated complications and hepatocellular carcinoma. It is now the most common liver disease in the Western world and its prevalence is increasing. While the association between NAFLD and type 2 diabetes has been well documented, there is significantly less understanding of the pathophysiology and progression of NAFLD in patients with other endocrine disorders affecting metabolism in various ways. Some of the more common endocrine disorders such as polycystic ovarian syndrome, growth hormone deficiency, hypothyroidism, and hypogonadism are known in clinical practice to be associated with NAFLD. Medications that alter the endocrine system such as tamoxifen and adrenal steroids have also been attributed to significant NAFLD. The key to management of NAFLD at this time are dietary changes and exercise to achieve weight loss. Unfortunately, a large proportion of the patients with these endocrine disorders are unable to achieve either. This review aims to examine and summarize the current published literature that have evaluated the association between NAFLD and the above endocrine disorders and potential therapeutic interventions in each case.

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

Down regulation of E-Cadherin (ECAD) - a predictor for occult metastatic disease in sentinel node biopsy of early squamous cell carcinomas of the oral cavity and oropharynx

PubMed Central

2011-01-01

Background Prognostic factors in predicting occult lymph node metastasis in patients with head and neck squamous-cell carcinoma (HNSCC) are necessary to improve the results of the sentinel lymph node procedure in this tumour type. The E-Cadherin glycoprotein is an intercellular adhesion molecule in epithelial cells, which plays an important role in establishing and maintaining intercellular connections. Objectives To determine the value of the molecular marker E-Cadherin in predicting regional metastatic disease. Methods E-Cadherin expression in tumour tissue of 120 patients with HNSCC of the oral cavity and oropharynx were evaluated using the tissue microarray technique. 110 tumours were located in the oral cavity (91.7%; mostly tongue), 10 tumours in the oropharynx (8.3%). Intensity of E-Cadherin expression was quantified by the Intensity Reactivity Score (IRS). These results were correlated with the lymph node status of biopsied sentinel lymph nodes. Univariate and multivariate analysis was used to determine statistical significance. Results pT-stage, gender, tumour side and location did not correlate with lymph node metastasis. Differentiation grade (p = 0.018) and down regulation of E-Cadherin expression significantly correlate with positive lymph node status (p = 0.005) in univariate and multivariate analysis. Conclusion These data suggest that loss of E-cadherin expression is associated with increased lymhogeneous metastasis of HNSCC. E-cadherin immunohistochemistry may be used as a predictor for lymph node metastasis in squamous cell carcinoma of the oral cavity and oropharynx. Level of evidence: 2b PMID:21639893

Down regulation of E-Cadherin (ECAD) - a predictor for occult metastatic disease in sentinel node biopsy of early squamous cell carcinomas of the oral cavity and oropharynx.

PubMed

Huber, Gerhard F; Züllig, Lena; Soltermann, Alex; Roessle, Matthias; Graf, Nicole; Haerle, Stephan K; Studer, Gabriela; Jochum, Wolfram; Moch, Holger; Stoeckli, Sandro J

2011-06-03

Prognostic factors in predicting occult lymph node metastasis in patients with head and neck squamous-cell carcinoma (HNSCC) are necessary to improve the results of the sentinel lymph node procedure in this tumour type. The E-Cadherin glycoprotein is an intercellular adhesion molecule in epithelial cells, which plays an important role in establishing and maintaining intercellular connections. To determine the value of the molecular marker E-Cadherin in predicting regional metastatic disease. E-Cadherin expression in tumour tissue of 120 patients with HNSCC of the oral cavity and oropharynx were evaluated using the tissue microarray technique. 110 tumours were located in the oral cavity (91.7%; mostly tongue), 10 tumours in the oropharynx (8.3%). Intensity of E-Cadherin expression was quantified by the Intensity Reactivity Score (IRS). These results were correlated with the lymph node status of biopsied sentinel lymph nodes. Univariate and multivariate analysis was used to determine statistical significance. pT-stage, gender, tumour side and location did not correlate with lymph node metastasis. Differentiation grade (p = 0.018) and down regulation of E-Cadherin expression significantly correlate with positive lymph node status (p = 0.005) in univariate and multivariate analysis. These data suggest that loss of E-cadherin expression is associated with increased lymhogeneous metastasis of HNSCC. E-cadherin immunohistochemistry may be used as a predictor for lymph node metastasis in squamous cell carcinoma of the oral cavity and oropharynx. 2b.

Obesity: an endocrine tumor?

PubMed

Dizdar, Omer; Alyamaç, Evrim

2004-01-01

Obesity is one of the most common disorders in clinical practice. The prevalance of obesity has increased by more than 60% since 1990. Adipose tissue acts as an endocrine organ secreting many factors into the blood, known as adipokines, including leptin, adipsin, acylation-stimulating protein, adiponectin, etc. This article examines the hypothesis that obesity may be evaluated as an endocrine tumor, regarding its genetic basis, hyperplasia and hypertrophy of adipocytes, neovascularisation within the adipose tissue associated with growth, and beneficisal metabolic effects of surgical removal of excess adipose tissue by liposuction. Assuming obesity as an endocrine tumor may bring out new treatment modalities. Liposuction as "cytoreductive surgery", antiangiogenic teraphy or anti-neoplastic drugs may be important components of obesity treatment in future.

[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.

Negative energy balance in a male songbird, the Abert's towhee, constrains the testicular endocrine response to luteinizing hormone stimulation

PubMed Central

Davies, Scott; Gao, Sisi; Valle, Shelley; Bittner, Stephanie; Hutton, Pierce; Meddle, Simone L.; Deviche, Pierre

2015-01-01

ABSTRACT Energy deficiency can suppress reproductive function in vertebrates. As the orchestrator of reproductive function, endocrine activity of the hypothalamo-pituitary–gonadal (HPG) axis is potentially an important mechanism mediating such effects. Previous experiments in wild-caught birds found inconsistent relationships between energy deficiency and seasonal reproductive function, but these experiments focused on baseline HPG axis activity and none have investigated the responsiveness of this axis to endocrine stimulation. Here, we present data from an experiment in Abert's towhees, Melozone aberti, using gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) challenges to investigate whether energy deficiency modulates the plasma testosterone responsiveness of the HPG axis. Wild-caught birds were either ad libitum fed or energetically constrained via chronic food restriction during photoinduced reproductive development. Energy deficiency did not significantly affect the development of reproductive morphology, the baseline endocrine activity of the HPG axis, or the plasma testosterone response to GnRH challenge. Energy deficiency did, however, decrease the plasma testosterone responsiveness to LH challenge. Collectively, these observations suggest that energy deficiency has direct gonadal effects consisting of a decreased responsiveness to LH stimulation. Our study, therefore, reveals a mechanism by which energy deficiency modulates reproductive function in wild birds in the absence of detectable effects on baseline HPG axis activity. PMID:26333925

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

Endocrine Dysregulation in Anorexia Nervosa Update

PubMed Central

2011-01-01

Context: Anorexia nervosa is a primary psychiatric disorder with serious endocrine consequences, including dysregulation of the gonadal, adrenal, and GH axes, and severe bone loss. This Update reviews recent advances in the understanding of the endocrine dysregulation observed in this state of chronic starvation, as well as the mechanisms underlying the disease itself. Evidence Acquisition: Findings of this update are based on a PubMed search and the author's knowledge of this field. Evidence Synthesis: Recent studies have provided insights into the mechanisms underlying endocrine dysregulation in states of chronic starvation as well as the etiology of anorexia nervosa itself. This includes a more complex understanding of the pathophysiologic bases of hypogonadism, hypercortisolemia, GH resistance, appetite regulation, and bone loss. Nevertheless, the etiology of the disease remains largely unknown, and effective therapies for the endocrine complications and for the disease itself are lacking. Conclusions: Despite significant progress in the field, further research is needed to elucidate the mechanisms underlying the development of anorexia nervosa and its endocrine complications. Such investigations promise to yield important advances in the therapeutic approach to this disease as well as to the understanding of the regulation of endocrine function, skeletal biology, and appetite regulation. PMID:21976742

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

PubMed Central

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

2015-01-01

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

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

Defining pancreatic endocrine precursors and their descendants.

PubMed

White, Peter; May, Catherine Lee; Lamounier, Rodrigo N; Brestelli, John E; Kaestner, Klaus H

2008-03-01

The global incidence of diabetes continues to increase. Cell replacement therapy and islet transplantation offer hope, especially for severely affected patients. Efforts to differentiate insulin-producing beta-cells from progenitor or stem cells require knowledge of the transcriptional programs that regulate the development of the endocrine pancreas. Differentiation toward the endocrine lineage is dependent on the transcription factor Neurogenin 3 (Neurog3, Ngn3). We utilize a Neurog3-enhanced green fluorescent protein knock-in mouse model to isolate endocrine progenitor cells from embryonic pancreata (embryonic day [E]13.5 through E17.5). Using advanced genomic approaches, we generate a comprehensive gene expression profile of these progenitors and their immediate descendants. A total of 1,029 genes were identified as being temporally regulated in the endocrine lineage during fetal development, 237 of which are transcriptional regulators. Through pathway analysis, we have modeled regulatory networks involving these proteins that highlight the complex transcriptional hierarchy governing endocrine differentiation. We have been able to accurately capture the gene expression profile of the pancreatic endocrine progenitors and their descendants. The list of temporally regulated genes identified in fetal endocrine precursors and their immediate descendants provides a novel and important resource for developmental biologists and diabetes researchers alike.

Endocrine Disruptors

MedlinePlus

... cans, detergents, flame retardants, food, toys, cosmetics, and pesticides. NIEHS supports studies to determine whether exposure to endocrine disruptors may result in human health effects including lowered fertility and an increased incidence ...

Multiple endocrine neoplasia type 1

PubMed Central

Marini, Francesca; Falchetti, Alberto; Monte, Francesca Del; Sala, Silvia Carbonell; Gozzini, Alessia; Luzi, Ettore; Brandi, Maria Luisa

2006-01-01

Multiple Endocrine Neoplasia type 1 (MEN1) is a rare autosomal dominant hereditary cancer syndrome presented mostly by tumours of the parathyroids, endocrine pancreas and anterior pituitary, and characterised by a very high penetrance and an equal sex distribution. It occurs in approximately one in 30,000 individuals. Two different forms, sporadic and familial, have been described. The sporadic form presents with two of the three principal MEN1-related endocrine tumours (parathyroid adenomas, entero-pancreatic tumours and pituitary tumours) within a single patient, while the familial form consists of a MEN1 case with at least one first degree relative showing one of the endocrine characterising tumours. Other endocrine and non-endocrine lesions, such as adrenal cortical tumours, carcinoids of the bronchi, gastrointestinal tract and thymus, lipomas, angiofibromas, collagenomas have been described. The responsible gene, MEN1, maps on chromosome 11q13 and encodes a 610 aminoacid nuclear protein, menin, with no sequence homology to other known human proteins. MEN1 syndrome is caused by inactivating mutations of the MEN1 tumour suppressor gene. This gene is probably involved in the regulation of several cell functions such as DNA replication and repair and transcriptional machinery. The combination of clinical and genetic investigations, together with the improving of molecular genetics knowledge of the syndrome, helps in the clinical management of patients. Treatment consists of surgery and/or drug therapy, often in association with radiotherapy or chemotherapy. Currently, DNA testing allows the early identification of germline mutations in asymptomatic gene carriers, to whom routine surveillance (regular biochemical and/or radiological screenings to detect the development of MEN1-associated tumours and lesions) is recommended. PMID:17014705

Cephalometric oropharynx and oral cavity analysis in Chiari malformation Type I: a retrospective case-control study.

PubMed

Urbizu, Aintzane; Ferré, Alex; Poca, Maria-Antonia; Rovira, Alex; Sahuquillo, Juan; Martin, Bryn A; Macaya, Alfons

2017-02-01

OBJECTIVE Traditionally, Chiari malformation Type I has been related to downward herniation of the cerebellar tonsils as a consequence of an underdeveloped posterior cranial fossa. Although the common symptoms of Chiari malformation Type I are occipital headaches, cervical pain, dizziness, paresthesia, and sensory loss, patients often report symptoms related to pharyngeal dysfunction such as choking, regurgitation, dysphagia, aspiration, chronic cough, and sleep disorders. In addition, tracheal intubation is often difficult in these patients. The purpose of this study was to analyze the morphological features of the oropharynx and oral cavity in patients with Chiari malformation Type I to help identify underlying anatomical anomalies leading to these debilitating symptoms. METHODS Seventy-six adult patients with symptomatic Chiari malformation Type I with cerebellar tonsillar descent greater than 5 mm below the foramen magnum and a small posterior cranial fossa and 49 sex-matched controls were selected to perform a retrospective case-control MRI-based morphometric study in a tertiary hospital. Eleven linear and areal parameters of the oropharyngeal cavity on midsagittal T1-weighted MRI were measured and the average values between patients and control cohorts were compared. Correlations between variables showing or approaching statistical significance in these structures and posterior cranial fossa measurements related with the occipital bone were sought. RESULTS Significant differences were detected for several oropharynx and oral cavity measures in the patient cohort, primarily involving the length and thickness of the soft palate (p = 9.5E-05 and p = 3.0E-03, respectively). A statistically significant (p < 0.01) moderate correlation between some of these variables and posterior cranial fossa parameters was observed. CONCLUSIONS The existence of structural oropharyngeal and oral cavity anomalies in patients with Chiari malformation Type I was confirmed, which may

New Roles of Carboxypeptidase E in Endocrine and Neural Function and Cancer

PubMed Central

Cawley, Niamh X.; Wetsel, William C.; Murthy, Saravana R. K.; Park, Joshua J.; Pacak, Karel

2012-01-01

Carboxypeptidase E (CPE) or carboxypeptidase H was first discovered in 1982 as an enkephalin-convertase that cleaved a C-terminal basic residue from enkephalin precursors to generate enkephalin. Since then, CPE has been shown to be a multifunctional protein that subserves many essential nonenzymatic roles in the endocrine and nervous systems. Here, we review the phylogeny, structure, and function of CPE in hormone and neuropeptide sorting and vesicle transport for secretion, alternative splicing of the CPE transcript, and single nucleotide polymorphisms in humans. With this and the analysis of mutant and knockout mice, the data collectively support important roles for CPE in the modulation of metabolic and glucose homeostasis, bone remodeling, obesity, fertility, neuroprotection, stress, sexual behavior, mood and emotional responses, learning, and memory. Recently, a splice variant form of CPE has been found to be an inducer of tumor growth and metastasis and a prognostic biomarker for metastasis in endocrine and nonendocrine tumors. PMID:22402194

Prediction of occult lymph node metastasis in squamous cell carcinoma of the oral cavity and the oropharynx using peritumoral Prospero homeobox protein 1 lymphatic nuclear quantification.

PubMed

Mermod, Maxime; Bongiovanni, Massimo; Petrova, Tatiana V; Dubikovskaya, Elena A; Simon, Christian; Tolstonog, Genrich; Monnier, Yan

2016-09-01

The use of lymphatic vessel density as a predictor of occult lymph node metastasis (OLNM) in head and neck squamous cell carcinoma (HNSCC) has never been reported. Staining of the specific lymphatic endothelial cells nuclear marker, PROX1, as an indicator of lymphatic vessel density was determined by counting the number of positive cells in squamous cell carcinomas (SCCs) of the oral cavity and the oropharynx with clinically negative necks. Correlation with histopathological data was established. Peritumoral PROX1 lymphatic nuclear count significantly correlated with the detection of OLNM in multivariate analysis (p < .005). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of this parameter was 60%, 95%, 85%, and 90%, respectively. Peritumoral PROX1 lymphatic nuclear count in primary SCCs of the oral cavity and the oropharynx allows accurate prediction of occult lymph node metastasis. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1407-1415, 2016. © 2016 Wiley Periodicals, Inc.

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

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. Copyright © 2012 Elsevier Inc. All rights reserved.

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 ...

A critical review of histopathological findings associated with endocrine and non-endocrine hepatic toxicity in fish models.

PubMed

Wolf, Jeffrey C; Wheeler, James R

2018-04-01

Although frequently examined as a target organ for non-endocrine toxicity, histopathological evaluation of the liver is becoming a routine component of endocrine disruption studies that utilize various fish species as test subjects. However, the interpretation of microscopic liver findings can be challenging, especially when attempting to distinguish adverse changes associated with endocrine disrupting substances from those caused by systemic or direct hepatic toxicity. The purpose of this project was to conduct a critical assessment of the available peer-reviewed and grey literature concerning the histopathologic effects of reproductive endocrine active substances (EAS) and non-endocrine acting substances in the livers of fish models, and to determine if liver histopathology can be used to reliably distinguish endocrine from non-endocrine etiologies. The results of this review suggest that few compound-specific histopathologic liver effects have been identified, among which are estrogen agonist-induced increases in hepatocyte basophilia and proteinaceous intravascular fluid in adult male teleosts, and potentially, decreased hepatocyte basophilia in female fish exposed to substances that possess androgenic, anti-estrogenic, or aromatase inhibitory activity. This review also used published standardized methodology to assess the credibility of the histopathology data in each of the 117 articles that reported liver effects of treatment, and consequently it was determined that in only 37% of those papers were the data considered either highly credible or credible. The outcome of this work highlights the value of histopathologic liver evaluation as an investigative tool for EAS studies, and provides information that may have implications for EAS hazard assessment. Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

Evaluation of diagnostic cytology via endoscopic naso-pancreatic drainage for pancreatic tumor

PubMed Central

Iwata, Tomoyuki; Kitamura, Katsuya; Yamamiya, Akira; Ishii, Yu; Sato, Yoshiki; Nomoto, Tomohiro; Ikegami, Akitoshi; Yoshida, Hitoshi

2014-01-01

AIM: To evaluate the usefulness of cytology of the pancreatic juice obtained via the endoscopic naso-pancreatic drainage tube (ENPD-C). METHODS: ENPD was performed in cases where a diagnosis could not be made other than by using endoscopic retrograde cholangiopancreatography and in cases of pancreatic neoplasms or cystic tumors, including intraductal papillary mucinous neoplasm (IPMN) suspected to have malignant potential. 35 patients (21 males and 14 females) underwent ENPD between January 2007 and June 2013. The pancreatic duct was imaged and the procedure continued in one of ENPD-C or ENPD-C plus brush cytology (ENPD-BC). We checked the cytology result and the final diagnosis. RESULTS: The mean patient age was 69 years (range, 48-86 years). ENPD-C was performed in 24 cases and ENPD-C plus brush cytology (ENPD-BC) in 11 cases. The ENPD tube was inserted for an average of 3.5 d. The final diagnosis was confirmed on the basis of the resected specimen in 18 cases and of follow-up findings at least 6 mo after ENPD in the 18 inoperable cases. Malignancy was diagnosed in 21 cases and 14 patients were diagnosed as having a benign condition. The ratios of class V/IV:III:II/I findings were 7:7:7 in malignant cases and 0:3:11 in benign cases. The sensitivity and specificity for all patients were 33.3% and 100%, respectively. The cytology-positive rate was 37.5% (6/16) for pancreatic cancer. For IPMN cases, the sensitivity and specificity were 33% and 100%, respectively. CONCLUSION: Sensitivity may be further increased by adding brush cytology. Although we can diagnosis cancer in cases of a positive result, the accuracy of ENPD-C remains unsatisfactory. PMID:25132920

An in vitro investigation of endocrine disrupting effects of the mycotoxin alternariol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frizzell, Caroline; Ndossi, Doreen; Sokoine University of Agriculture, Morogoro

2013-08-15

Alternariol (AOH) is a mycotoxin commonly produced by Alternaria alternata on a wide range of foods. Few studies to date have been performed to evaluate the effects of AOH on endocrine activity. The present study makes use of in vitro mammalian cellular based assays and gene expression to investigate the ability of AOH to act as an endocrine disruptor by various modes of action. Reporter gene assays (RGAs), incorporating natural steroid hormone receptors for oestrogens, androgens, progestagens and glucocorticoids were used to identify endocrine disruption at the level of nuclear receptor transcriptional activity, and the H295R steroidogenesis assay was usedmore » to assess endocrine disruption at the level of gene expression and steroid hormone production. AOH exhibited a weak oestrogenic response when tested in the oestrogen responsive RGA and binding of progesterone to the progestagen receptor was shown to be synergistically increased in the presence of AOH. H295R cells when exposed to 0.1–1000 ng/ml AOH, did not cause a significant change in testosterone and cortisol hormones but exposure to 1000 ng/ml (3.87 μM) AOH resulted in a significant increase in estradiol and progesterone production. In the gene expression study following exposure to 1000 ng/ml (3.87 μM) AOH, only one gene NR0B1 was down-regulated, whereas expression of mRNA for CYP1A1, MC2R, HSD3B2, CYP17, CYP21, CYP11B2 and CYP19 was up-regulated. Expression of the other genes investigated did not change significantly. In conclusion AOH is a weak oestrogenic mycotoxin that also has the ability to interfere with the steroidogenesis pathway. - Highlights: • Alternariol was investigated for endocrine disrupting activity. • Reporter gene assays and the H295R steroidogenesis assay have been used. • An oestrogenic effect of alternariol was observed. • This can lead to an increase in expression of the progesterone receptor. • Alternariol is capable of modulating hormone production and gene

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. Copyright © 2011 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

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...

Negative energy balance in a male songbird, the Abert's Towhee, constrains the testicular endocrine response to luteinizing hormone stimulation.

PubMed

Davies, Scott; Gao, Sisi; Valle, Shelley; Bittner, Stephanie; Hutton, Pierce; Meddle, Simone L; Deviche, Pierre

2015-07-10

Energy deficiency can suppress reproductive functions in vertebrates. As the orchestrator of reproductive function, endocrine activity of the hypothalamo-pituitary-gonadal (HPG) axis is potentially an important mechanism mediating such effects. Previous experiments in wild-caught birds found inconsistent relationships between energy deficiency and seasonal reproductive function, but these experiments focused on baseline HPG axis activity and none has investigated the responsiveness of this axis to endocrine stimulation. Here, we present data from an experiment in Abert's Towhees, Melozone aberti, using gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) challenges to investigate whether energy deficiency modulates the plasma testosterone (T) responsiveness of the HPG axis. Wild-caught birds were either ad libitum-fed or energetically constrained via chronic food restriction during photoinduced reproductive development. Energy deficiency did not significantly affect the development of reproductive morphology, the baseline endocrine activity of the HPG axis, or the plasma T response to GnRH challenge. Energy deficiency did, however, decrease the plasma T responsiveness to LH challenge. Collectively, these observations suggest that energy deficiency has direct gonadal effects consisting in decreased responsiveness to LH stimulation. Our study, therefore, reveals a mechanism by which energy deficiency modulates reproductive function in wild birds in the absence of detectable effects on baseline HPG axis activity. © 2015. Published by The Company of Biologists Ltd.

Negative energy balance in a male songbird, the Abert's towhee, constrains the testicular endocrine response to luteinizing hormone stimulation.

PubMed

Davies, Scott; Gao, Sisi; Valle, Shelley; Bittner, Stephanie; Hutton, Pierce; Meddle, Simone L; Deviche, Pierre

2015-09-01

Energy deficiency can suppress reproductive function in vertebrates. As the orchestrator of reproductive function, endocrine activity of the hypothalamo-pituitary-gonadal (HPG) axis is potentially an important mechanism mediating such effects. Previous experiments in wild-caught birds found inconsistent relationships between energy deficiency and seasonal reproductive function, but these experiments focused on baseline HPG axis activity and none have investigated the responsiveness of this axis to endocrine stimulation. Here, we present data from an experiment in Abert's towhees, Melozone aberti, using gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) challenges to investigate whether energy deficiency modulates the plasma testosterone responsiveness of the HPG axis. Wild-caught birds were either ad libitum fed or energetically constrained via chronic food restriction during photoinduced reproductive development. Energy deficiency did not significantly affect the development of reproductive morphology, the baseline endocrine activity of the HPG axis, or the plasma testosterone response to GnRH challenge. Energy deficiency did, however, decrease the plasma testosterone responsiveness to LH challenge. Collectively, these observations suggest that energy deficiency has direct gonadal effects consisting of a decreased responsiveness to LH stimulation. Our study, therefore, reveals a mechanism by which energy deficiency modulates reproductive function in wild birds in the absence of detectable effects on baseline HPG axis activity. © 2015. Published by The Company of Biologists Ltd.

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

Endocrine and Metabolic Aspects of Tuberculosis

PubMed Central

Vinnard, Christopher; Blumberg, Emily A.

2017-01-01

Endocrine and metabolic derangements are infrequent in patients with tuberculosis, but they are important when they occur. The basis for these abnormalities is complex. While Mycobacterium tuberculosis has been described to infect virtually every endocrine gland, the incidence of gland involvement is low, especially in the era of effective antituberculosis therapy. Furthermore, endocrine and metabolic abnormalities do not always reflect direct infection of the gland but may result from physiological response or as a consequence of therapy. Metabolic disease may also predispose patients to the development of active tuberculosis, particularly in the case of diabetes mellitus. While hormonal therapy may be necessary in some instances, frequently these endocrine complications do not require specific interventions other than antituberculous therapy itself. With the exception of diabetes mellitus, which will be covered elsewhere, this chapter reviews the endocrinologic and metabolic issues related to tuberculosis. PMID:28233510

[Diabetes and prediabetes in endocrine disorders].

PubMed

Krysiak, Robert; Rudzki, Henryk; Okopień, Bogusław

2012-01-01

Complex hormonal regulation of carbohydrate metabolism causes that presence of many endocrine disorders may disturb glucose homeostasis. Impaired fasting glucose, impaired glucose tolerance and frank diabetes are observed in patients with both common and rare endocrine disorders, particularly in patients with polycystic ovary syndrome, hyperthyroidism, Cushing's syndrome, pheochromocytoma, primary aldosteronism, acromegaly, growth hormone deficiency and endocrine tumors of the digestive system. Because most of these disorders may be effectively treated and the treatment often results in a restoration of normal insulin secretion and receptor action as well as glucose absorption, production and metabolism, it is important to differentiate these disorders from other more common types of diabetes. This article reviews the etiology, clinical manifestation, diagnosis and management of endocrine disorders leading to diabetes and prediabetic states with special emphasis on the pathogenesis and clinical consequences of these disorders.

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...

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

Endocrine system: part 2.

PubMed

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

2014-06-03

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.

Endocrine-Disrupting Chemicals and Public Health Protection: A Statement of Principles from The Endocrine Society

PubMed Central

Brown, T. R.; Doan, L. L.; Gore, A. C.; Skakkebaek, N. E.; Soto, A. M.; Woodruff, T. J.; Vom Saal, F. S.

2012-01-01

An endocrine-disrupting chemical (EDC) is an exogenous chemical, or mixture of chemicals, that can interfere with any aspect of hormone action. The potential for deleterious effects of EDC must be considered relative to the regulation of hormone synthesis, secretion, and actions and the variability in regulation of these events across the life cycle. The developmental age at which EDC exposures occur is a critical consideration in understanding their effects. Because endocrine systems exhibit tissue-, cell-, and receptor-specific actions during the life cycle, EDC can produce complex, mosaic effects. This complexity causes difficulty when a static approach to toxicity through endocrine mechanisms driven by rigid guidelines is used to identify EDC and manage risk to human and wildlife populations. We propose that principles taken from fundamental endocrinology be employed to identify EDC and manage their risk to exposed populations. We emphasize the importance of developmental stage and, in particular, the realization that exposure to a presumptive “safe” dose of chemical may impact a life stage when there is normally no endogenous hormone exposure, thereby underscoring the potential for very low-dose EDC exposures to have potent and irreversible effects. Finally, with regard to the current program designed to detect putative EDC, namely, the Endocrine Disruptor Screening Program, we offer recommendations for strengthening this program through the incorporation of basic endocrine principles to promote further understanding of complex EDC effects, especially due to developmental exposures. PMID:22733974

Symptom burden and dysphagia associated with osteoradionecrosis in long-term oropharynx cancer survivors: A cohort analysis.

PubMed

Wong, Angela T T; Lai, Stephen Y; Gunn, G Brandon; Beadle, Beth M; Fuller, Clifton D; Barrow, Martha P; Hofstede, Theresa M; Chambers, Mark S; Sturgis, Erich M; Mohamed, Abdallah Sherif Radwan; Lewin, Jan S; Hutcheson, Katherine A

2017-03-01

The purpose is to examine the relationship between mandibular osteoradionecrosis (ORN) and chronic dysphagia in long-term oropharynx cancer (OPC) survivors, and to determine the perceived symptom burden associated with ORN. Medical records of 349 OPC patients treated with bilateral IMRT and systemic therapy were reviewed. ORN was graded using a published 4-point classification schema. Patients were considered to have chronic dysphagia if they had aspiration pneumonia, stricture or aspiration detected by fluoroscopy or endoscopy, and/or feeding tube dependence in long-term follow-up ⩾1year following radiotherapy. MD Anderson Symptom Inventory - Head and Neck Module (MDASI-HN) scores were analyzed in a nested cross-sectional survey sample of 118 patients. 34 (9.7%, 95% CI: 6.8-13.3%) patients developed ORN and 45 (12.9%, 95% CI: 9.6-16.9%) patients developed chronic dysphagia. Prevalence of chronic dysphagia was significantly higher in ORN cases (12/34, 35%) compared to those who did not develop ORN (33/315, 11%, p<0.001). ORN grade was also significantly associated with prevalence of dysphagia (p<0.001); the majority of patients with grade 4 ORN requiring major surgery (6 patients, 75%) were found to have chronic dysphagia. Summary MDASI-HN symptom scores did not significantly differ by ORN grade. Significantly higher symptom burden was reported, however, among ORN cases compared to those without ORN for MDASI-HN swallowing (p=0.033), problems with teeth and/or gums (p=0.016) and change in activity (p=0.015) item scores. ORN is associated with excess burden of chronic dysphagia and higher symptom severity related to swallowing, dentition and activity limitations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Symptom burden and dysphagia associated with osteoradionecrosis in long-term oropharynx cancer survivors: a cohort analysis

PubMed Central

Wong, Angela T. T.; Lai, Stephen Y.; Gunn, G. Brandon; Beadle, Beth M.; Fuller, Clifton D.; Barrow, Martha P.; Hofstede, Theresa M.; Chambers, Mark S.; Sturgis, Erich M.; Mohamed, Abdallah Sherif Radwan; Lewin, Jan S.; Hutcheson, Katherine A.

2017-01-01

Objective The purpose is to examine the relationship between mandibular osteoradionecrosis (ORN) and chronic dysphagia in long-term oropharynx cancer (OPC) survivors and to determine the perceived symptom burden associated with ORN. Materials and Methods Medical records of 349 OPC patients treated with bilateral IMRT and systemic therapy were reviewed. ORN was graded using a published 4-point classification schema. Patients were considered to have chronic dysphagia if they had aspiration pneumonia, stricture or aspiration detected by fluoroscopy or endoscopy, and/or feeding tube dependence in long-term follow-up ≥ 1 year following radiotherapy. MD Anderson Symptom Inventory – Head and Neck Module (MDASI-HN) scores were analyzed in a nested cross-sectional survey sample of 118 patients. Results 34 (9.7%, 95% CI: 6.8–13.3%) patients developed ORN and 45 (12.9%, 95% CI: 9.6–16.9%) patients developed chronic dysphagia. Prevalence of chronic dysphagia was significantly higher in ORN cases (12/34, 35%) compared to those who did not develop ORN (33/315, 11%, p<0.001). ORN grade was also significantly associated with prevalence of dysphagia (p<0.001); the majority of patients with grade 4 ORN requiring major surgery (6 patients, 75%) were found to have chronic dysphagia. Summary MDASI-HN symptom scores did not significantly differ by ORN grade. Significantly higher symptom burden was reported, however, among ORN cases compared to those without ORN for MDASI-HN swallowing (p=0.033), problems with teeth and/or gums (p=0.016) and change in activity (p=0.015) item scores. Conclusions ORN is associated with excess burden of chronic dysphagia and higher symptom severity related to swallowing, dentition and activity limitations. PMID:28249651

Psychosocial approach to endocrine disease.

PubMed

Sonino, Nicoletta; Tomba, Elena; Fava, Giovanni A

2007-01-01

In recent years, there has been growing interest in the psychosocial aspects of endocrine disease, such as the role of life stress in the pathogenesis of some conditions, their association with affective disorders, and the presence of residual symptoms after adequate treatment. In clinical endocrinology, exploration of psychosocial antecedents may elucidate the temporal relationships between life events and symptom onset, as it has been shown to be relevant for pituitary (Cushing's disease, hyperprolactinemia) or thyroid (Graves' disease) conditions, as well as the role of allostatic load, linked to chronic stress, in uncovering a person's vulnerability. After endocrine abnormalities are established, they are frequently associated with a wide range of psychological symptoms: at times, such symptoms reach the level of psychiatric illness (mainly mood and anxiety disorders); at other times, however, they can only be identified by the subclinical forms of assessment provided by the Diagnostic Criteria for Psychosomatic Research (DCPR). Indeed, in a population study, the majority of patients suffered from at least one of the three DCPR syndromes considered: irritable mood, demoralization, persistent somatization. In particular, irritable mood was found to occur in 46% of 146 patients successfully treated for endocrine conditions, a rate similar to that found in cardiology and higher than in oncology and gastroenterology. Long-standing endocrine disorders may imply a degree of irreversibility of the pathological process and induce highly individualized affective responses. In patients who showed persistence or even worsening of psychological distress upon proper endocrine treatment, the value of appropriate psychiatric interventions was underscored. As it happened in other fields of clinical medicine, a conceptual shift from a merely biomedical care to a psychosomatic consideration of the person and his/her quality of life appears to be necessary for improving

Endocrine Disruptors in Domestic Animal Reproduction: A Clinical Issue?

PubMed Central

Magnusson, Ulf; Persson, Sara

2015-01-01

Contents The objective of this review was to discuss whether endocrine disruption is a clinical concern in domestic animal reproduction. To that end, we firstly summarize the phenomenon of endocrine disruption, giving examples of the agents of concern and their effects on the mammalian reproductive system. Then there is a brief overview of the literature on endocrine disruptors and domestic animal reproduction. Finally, the clinical implications of endocrine disruptors on the reproductive system of farm animals as well as in dogs and cats are discussed. It is concluded that the evidence for clinical cases of endocrine disruption by chemical pollutants is weak, whereas for phytooestrogens, it is well established. However, there is concern that particular dogs and cats may be exposed to man-made endocrine disruptors. PMID:26382024

Autoimmunity in endocrine diseases.

PubMed

Rose, N R; Burek, C L

1982-01-01

The realization that autoimmunity underlies many endocrine disorders of previously unknown etiology has greatly broadened our understanding of the pathogenesis of these diseases. It has provided new explanations for their heredity and their association with particular HLA haplotypes. It has also offered new tools for diagnosing these diseases as well as monitoring their course or predicting their outcome. Finally, establishing the autoimmune basis of these diseases offers new potential for their treatment. The next quarter century of research into immunologic aspects of endocrine diseases promises to be as fruitful as the last.

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

Contextual modulation of social and endocrine correlates of fitness: insights from the life history of a sex changing fish.

PubMed

Pradhan, Devaleena S; Solomon-Lane, Tessa K; Grober, Matthew S

2015-01-01

Steroid hormones are critical regulators of reproductive life history, and the steroid sensitive traits (morphology, behavior, physiology) associated with particular life history stages can have substantial fitness consequences for an organism. Hormones, behavior and fitness are reciprocally associated and can be used in an integrative fashion to understand how the environment impacts organismal function. To address the fitness component, we highlight the importance of using reliable proxies of reproductive success when studying proximate regulation of reproductive phenotypes. To understand the mechanisms by which the endocrine system regulates phenotype, we discuss the use of particular endocrine proxies and the need for appropriate functional interpretation of each. Lastly, in any experimental paradigm, the responses of animals vary based on the subtle differences in environmental and social context and this must also be considered. We explore these different levels of analyses by focusing on the fascinating life history transitions exhibited by the bi-directionally hermaphroditic fish, Lythrypnus dalli. Sex changing fish are excellent models for providing a deeper understanding of the fitness consequences associated with behavioral and endocrine variation. We close by proposing that local regulation of steroids is one potential mechanism that allows for the expression of novel phenotypes that can be characteristic of specific life history stages. A comparative species approach will facilitate progress in understanding the diversity of mechanisms underlying the contextual regulation of phenotypes and their associated fitness correlates.

Hippocampus Contributions to Food Intake Control: Mnemonic, Neuroanatomical, and Endocrine Mechanisms.

PubMed

Kanoski, Scott E; Grill, Harvey J

2017-05-01

Food intake is a complex behavior that can occur or cease to occur for a multitude of reasons. Decisions about where, when, what, and how much to eat are not merely reflexive responses to food-relevant stimuli or to changes in energy status. Rather, feeding behavior is modulated by various contextual factors and by previous experiences. The data reviewed here support the perspective that neurons in multiple hippocampal subregions constitute an important neural substrate linking the external context, the internal context, and mnemonic and cognitive information to control both appetitive and ingestive behavior. Feeding behavior is heavily influenced by hippocampal-dependent mnemonic functions, including episodic meal-related memories and conditional learned associations between food-related stimuli and postingestive consequences. These mnemonic processes are undoubtedly influenced by both external and internal factors relating to food availability, location, and physiological energy status. The afferent and efferent neuroanatomical connectivity of the subregions of the hippocampus is reviewed with regard to the integration of visuospatial and olfactory sensory information (the external context) with endocrine and gastrointestinal interoceptive stimuli (the internal context). Also discussed are recent findings demonstrating that peripherally derived endocrine signals act on receptors in hippocampal neurons to reduce (leptin, glucagon-like peptide-1) or increase (ghrelin) food intake and learned food reward-driven responding, thereby highlighting endocrine and neuropeptidergic signaling in hippocampal neurons as a novel substrate of importance in the higher-order regulation of feeding behavior. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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. Published by Elsevier B.V.

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

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. Copyright © 2010 SEEN. Published by Elsevier Espana. All rights reserved.

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...

Precommitment low-level Neurog3 expression defines a long-lived mitotic endocrine-biased progenitor pool that drives production of endocrine-committed cells

PubMed Central

Bechard, Matthew E.; Bankaitis, Eric D.; Hipkens, Susan B.; Ustione, Alessandro; Piston, David W.; Yang, Yu-Ping; Magnuson, Mark A.; Wright, Christopher V.E.

2016-01-01

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 Neurog3TA.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+ Neurog3TA.LO progenitors, associated with progenitor pool maintenance or derivation of endocrine-committed Neurog3HI cells, respectively. Moreover, limiting Neurog3 expression dramatically increased the proportional representation of Sox9+ Neurog3TA.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+ Neurog3TA.LO endocrine-biased progenitors feed production of Neurog3HI endocrine-committed cells during pancreas organogenesis. PMID:27585590

Endocrine Disrupting Chemicals and Disease Susceptibility

PubMed Central

Schug, Thaddeus T.; Janesick, Amanda; Blumberg, Bruce; Heindel, Jerrold J.

2011-01-01

Environmental chemicals have significant impacts on biological systems. Chemical exposures during early stages of development can disrupt normal patterns of development and thus dramatically alter disease susceptibility later in life. Endocrine disrupting chemicals (EDCs) interfere with the body's endocrine system and produce adverse developmental, reproductive, neurological, cardiovascular, metabolic and immune effects in humans. A wide range of substances, both natural and man-made, are thought to cause endocrine disruption, including pharmaceuticals, dioxin and dioxin-like compounds, polychlorinated biphenyls, DDT and other pesticides, and components of plastics such as bisphenol A (BPA) and phthalates. EDCs are found in many everyday products– including plastic bottles, metal food cans, detergents, flame retardants, food additives, toys, cosmetics, and pesticides. EDCs interfere with the synthesis, secretion, transport, activity, or elimination of natural hormones. This interference can block or mimic hormone action, causing a wide range of effects. This review focuses on the mechanisms and modes of action by which EDCs alter hormone signaling. It also includes brief overviews of select disease endpoints associated with endocrine disruption. PMID:21899826

Endocrine disrupting chemicals and disease susceptibility.

PubMed

Schug, Thaddeus T; Janesick, Amanda; Blumberg, Bruce; Heindel, Jerrold J

2011-11-01

Environmental chemicals have significant impacts on biological systems. Chemical exposures during early stages of development can disrupt normal patterns of development and thus dramatically alter disease susceptibility later in life. Endocrine disrupting chemicals (EDCs) interfere with the body's endocrine system and produce adverse developmental, reproductive, neurological, cardiovascular, metabolic and immune effects in humans. A wide range of substances, both natural and man-made, are thought to cause endocrine disruption, including pharmaceuticals, dioxin and dioxin-like compounds, polychlorinated biphenyls, DDT and other pesticides, and components of plastics such as bisphenol A (BPA) and phthalates. EDCs are found in many everyday products--including plastic bottles, metal food cans, detergents, flame retardants, food additives, toys, cosmetics, and pesticides. EDCs interfere with the synthesis, secretion, transport, activity, or elimination of natural hormones. This interference can block or mimic hormone action, causing a wide range of effects. This review focuses on the mechanisms and modes of action by which EDCs alter hormone signaling. It also includes brief overviews of select disease endpoints associated with endocrine disruption. Published by Elsevier Ltd.

Menin determines K-RAS proliferative outputs in endocrine cells

PubMed Central

Chamberlain, Chester E.; Scheel, David W.; McGlynn, Kathleen; Kim, Hail; Miyatsuka, Takeshi; Wang, Juehu; Nguyen, Vinh; Zhao, Shuhong; Mavropoulos, Anastasia; Abraham, Aswin G.; O’Neill, Eric; Ku, Gregory M.; Cobb, Melanie H.; Martin, Gail R.; German, Michael S.

2014-01-01

Endocrine cell proliferation fluctuates dramatically in response to signals that communicate hormone demand. The genetic alterations that override these controls in endocrine tumors often are not associated with oncogenes common to other tumor types, suggesting that unique pathways govern endocrine proliferation. Within the pancreas, for example, activating mutations of the prototypical oncogene KRAS drive proliferation in all pancreatic ductal adenocarcimomas but are never found in pancreatic endocrine tumors. Therefore, we asked how cellular context impacts K-RAS signaling. We found that K-RAS paradoxically suppressed, rather than promoted, growth in pancreatic endocrine cells. Inhibition of proliferation by K-RAS depended on antiproliferative RAS effector RASSF1A and blockade of the RAS-activated proproliferative RAF/MAPK pathway by tumor suppressor menin. Consistent with this model, a glucagon-like peptide 1 (GLP1) agonist, which stimulates ERK1/2 phosphorylation, did not affect endocrine cell proliferation by itself, but synergistically enhanced proliferation when combined with a menin inhibitor. In contrast, inhibition of MAPK signaling created a synthetic lethal interaction in the setting of menin loss. These insights suggest potential strategies both for regenerating pancreatic β cells for people with diabetes and for targeting menin-sensitive endocrine tumors. PMID:25133424

Screening of oropharynx and anorectum increases prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae infection in female STD clinic visitors.

PubMed

Peters, Remco P H; Nijsten, Noëmi; Mutsaers, Johan; Jansen, Casper L; Morré, Servaas A; van Leeuwen, A Petra

2011-09-01

The relevance of screening of oropharynx and anorectum in addition to endocervical tests for detection of Chlamydia trachomatis and Neisseria gonorrhoeae infection is unclear in women, while there is a documented benefit of this approach in men who have sex with men. Female visitors to the sexually transmitted disease (STD) clinic were asked about their sexual practice as a part of the routine electronic patient file. In addition to tests for endocervical infection, swabs were taken from the oropharynx and anorectum to test for C. trachomatis and N. gonorrhoeae based on the history of sexual contact. Routinely, all electronic patient files are anonymously included in a database for surveillance purposes. In this observational study, we analyzed all consultations in the database over an 18 months period. A total of 4299 consultations were registered; 10% of women had endocervical chlamydia and 1.1% had gonorrhea. The detection rates for C. trachomatis and N. gonorrhoeae from oropharyngeal samples were 1.9% and 0.8%, and from anorectal samples 8.7% and 1.7%, respectively. Except for 2 cases of pharyngeal gonorrhea, all oropharyngeal and anorectal infections were asymptomatic. Inclusion of oropharyngeal and anorectal tests in the screening protocol was associated with a percentage increase in prevalence of chlamydia by 9.5% and gonorrhea by 31%, relative to tests for endocervical tests alone. The percentage increase in prevalence was higher than that for the symptom-based approach (3.7% and 10.4%, respectively). Inclusion of oropharyngeal and anorectal tests in the STD screening protocol increases the prevalence of chlamydia and gonorrhea in women. Screening of anatomical sites based on sexual history is preferred over a symptom-based protocol.

Predicting the risk of multiple endocrine neoplasia type 1 for patients with commonly occurring endocrine tumors.

PubMed

de Laat, Joanne M; Tham, Emma; Pieterman, Carolina R C; Vriens, Menno R; Dorresteijn, Johannes A N; Bots, Michiel L; Nordenskjöld, Magnus; van der Luijt, Rob B; Valk, Gerlof D

2012-08-01

Endocrine diseases that can be part of the rare inheritable syndrome multiple endocrine neoplasia type 1 (MEN1) commonly occur in the general population. Patients at risk for MEN1, and consequently their families, must be identified to prevent morbidity through periodic screening for the detection and treatment of manifestations in an early stage. The aim of the study was to develop a model for predicting MEN1 in individual patients with sporadically occurring endocrine tumors. Cross-sectional study. In a nationwide study in The Netherlands, patients with sporadically occurring endocrine tumors in whom the referring physician suspected the MEN1 syndrome were identified between 1998 and 2011 (n=365). Logistic regression analysis with internal validation using bootstrapping and external validation with a cohort from Sweden was used. A MEN1 mutation was found in 15.9% of 365 patients. Recurrent primary hyperparathyroidism (pHPT; odds ratio (OR) 162.40); nonrecurrent pHPT (OR 25.78); pancreatic neuroendocrine tumors (pNETs) and duodenal NETs (OR 17.94); pituitary tumor (OR 4.71); NET of stomach, thymus, or bronchus (OR 25.84); positive family history of NET (OR 4.53); and age (OR 0.96) predicted MEN1. The c-statistic of the prediction model was 0.86 (95% confidence interval (95% CI) 0.81-0.90) in the derivation cohort and 0.77 (95% CI 0.66-0.88) in the validation cohort. With the prediction model, the risk of MEN1 can be calculated in patients suspected for MEN1 with sporadically occurring endocrine tumors.

Contextual modulation of social and endocrine correlates of fitness: insights from the life history of a sex changing fish

PubMed Central

Pradhan, Devaleena S.; Solomon-Lane, Tessa K.; Grober, Matthew S.

2015-01-01

Steroid hormones are critical regulators of reproductive life history, and the steroid sensitive traits (morphology, behavior, physiology) associated with particular life history stages can have substantial fitness consequences for an organism. Hormones, behavior and fitness are reciprocally associated and can be used in an integrative fashion to understand how the environment impacts organismal function. To address the fitness component, we highlight the importance of using reliable proxies of reproductive success when studying proximate regulation of reproductive phenotypes. To understand the mechanisms by which the endocrine system regulates phenotype, we discuss the use of particular endocrine proxies and the need for appropriate functional interpretation of each. Lastly, in any experimental paradigm, the responses of animals vary based on the subtle differences in environmental and social context and this must also be considered. We explore these different levels of analyses by focusing on the fascinating life history transitions exhibited by the bi-directionally hermaphroditic fish, Lythrypnus dalli. Sex changing fish are excellent models for providing a deeper understanding of the fitness consequences associated with behavioral and endocrine variation. We close by proposing that local regulation of steroids is one potential mechanism that allows for the expression of novel phenotypes that can be characteristic of specific life history stages. A comparative species approach will facilitate progress in understanding the diversity of mechanisms underlying the contextual regulation of phenotypes and their associated fitness correlates. PMID:25691855

The endocrine effects of nicotine and cigarette smoke

PubMed Central

Tweed, Jesse Oliver; Hsia, Stanley H.; Lutfy, Kabirullah; Friedman, Theodore C.

2012-01-01

With a current prevalence of approximately 20%, smoking continues to impact negatively upon health. Tobacco or nicotine use influences the endocrine system, with important clinical implications. In this review we critically evaluate the literature concerning the impact of nicotine as well as tobacco use on several parameters of the endocrine system and on glucose and lipid homeostasis. Emphasis is on the effect of smoking on diabetes mellitus and obesity and the consequences of smoking cessation on these disorders. Understanding the effects of nicotine and cigarettes on the endocrine system and how these changes contribute to the pathogenesis of various endocrine diseases will allow for targeted therapies and more effective approaches for smoking cessation. PMID:22561025

Endocrine Abnormalities in Patients with Chronic Kidney Disease.

PubMed

Kuczera, Piotr; Adamczak, Marcin; Wiecek, Andrzej

2015-01-01

In patients with chronic kidney disease the alterations of the endocrine system may arise from several causes. The kidney is the site of degradation as well as synthesis of many different hormones. Moreover, a number of concomitant pathological conditions such as inflammation, metabolic acidosis and malnutrition may participate in the pathogenesis of endocrine abnormalities in this group of patients. The most pronounced endocrine abnormalities in patients with chronic kidney disease are the deficiencies of: calcitriol, testosterone, insulin-like growth factor and, erythropoietin (EPO). Additionally accumulation of several hormones, such as: prolactin, growth hormone and insulin frequently also occur. The clinical consequences of the abovementioned endocrine abnormalities are among others: anemia, infertility and bone diseases.

Endocrine Glands and Hearing: Auditory Manifestations of Various Endocrine and Metabolic Conditions

PubMed Central

Cherian, Kripa Elizabeth; Kapoor, Nitin; Mathews, Suma Susan; Paul, Thomas Vizhalil

2017-01-01

The aetiology of hearing loss in humans is multifactorial. Besides genetic, environmental and infectious causes, several endocrine and metabolic abnormalities are associated with varying degrees of hearing impairment. The pattern of hearing loss may be conductive, sensori-neural or mixed. The neurophysiology of hearing as well as the anatomical structure of the auditory system may be influenced by changes in the hormonal and metabolic milieu. Optimal management of these conditions requires the integrated efforts of the otolaryngologist and the endocrinologist. The presence of hearing loss especially in the young age group should prompt the clinician to explore the possibility of an associated endocrine or metabolic disorder for timely referral and early initiation of treatment. PMID:28553606

Multiple endocrine diseases in dogs: 35 cases (1996-2009).

PubMed

Blois, Shauna L; Dickie, Erica; Kruth, Stephen A; Allen, Dana G

2011-06-15

To characterize a population of dogs from a tertiary care center with 2 or more endocrine disorders, including the specific disorders and time intervals between diagnosis of each disorder. Retrospective case series. 35 dogs with 2 or more endocrine disorders. Medical records were reviewed, and the following was recorded: clinical signs, physical examination findings, and the results of CBC, serum biochemical analysis, urinalysis, aerobic bacterial culture of urine samples, endocrine testing, diagnostic imaging, and necropsy. 35 dogs with more than 1 endocrine disorder were identified. Seventy-seven percent (27/35) of the dogs were male, and the mean age at the time of diagnosis of the first endocrinopathy was 7.9 years. Miniature Schnauzer was the most common breed. Twenty-eight of 35 (80%) dogs had 2 disorders; 7 (20%) had 3 disorders. The most common combinations of disorders included diabetes mellitus and hyperadrenocorticism in 57.1 % (20/35) of dogs; hypoadrenocorticism and hypothyroidism in 22.9% (8/35) of dogs; and diabetes mellitus and hypothyroidism in 28.6% (10/35) of dogs. A mean of 14.5 months elapsed between diagnosis of the first and second endocrine disorders, whereas there was a mean of 31.1 months between diagnosis of the first and third endocrine disorders. Results suggested that the occurrence of multiple endocrine disorders was uncommon in dogs. The most common combinations of endocrine disorders in this population of dogs were diabetes mellitus and hyperadrenocorticism, followed by hypoadrenocorticism and hypothyroidism.

Differential levels of Neurod establish zebrafish endocrine pancreas cell fates

PubMed Central

Dalgin, Gökhan; Prince, Victoria E.

2015-01-01

During development a network of transcription factors functions to differentiate foregut cells into pancreatic endocrine cells. Differentiation of appropriate numbers of each hormone-expressing endocrine cell type is essential for the normal development of the pancreas and ultimately for effective maintenance of blood glucose levels. A fuller understanding of the details of endocrine cell differentiation may contribute to development of cell replacement therapies to treat diabetes. In this study, by using morpholino and gRNA/Cas9 mediated knockdown we establish that differential levels of the basic-helix loop helix (bHLH) transcription factor Neurod are required for the differentiation of distinct endocrine cell types in developing zebrafish. While Neurod plays a role in the differentiation of all endocrine cells, we find that differentiation of glucagon-expressing alpha cells is disrupted by a minor reduction in Neurod levels, whereas differentiation of insulin-expressing beta cells is less sensitive to Neurod depletion. The endocrine cells that arise during embryonic stages to produce the primary islet, and those that arise subsequently during larval stages from the intra-pancreatic duct (IPD) to ultimately contribute to the secondary islets, show similar dependence on differential Neurod levels. Intriguingly, Neurod-deficiency triggers premature formation of endocrine precursors from the IPD during early larval stages. However, the Neurod-deficient endocrine precursors fail to differentiate appropriately, and the larvae are unable to maintain normal glucose levels. In summary, differential levels of Neurod are required to generate endocrine pancreas subtypes from precursors during both embryonic and larval stages, and Neurod function is in turn critical to endocrine function. PMID:25797153

The clandestine organs of the endocrine system.

PubMed

Garcia-Reyero, Natàlia

2018-02-01

This review analyzes what could be regarded as the "clandestine organs" of the endocrine system: the gut microbiome, the immune system, and the stress system. The immune system is very closely related to the endocrine system, with many intertwined processes and signals. Many researchers now consider the microbiome as an 'organ' that affects the organism at many different levels. While stress is certainly not an organ, it affects so many processes, including endocrine-related processes, that the stress response system deserved a special section in this review. Understanding the connections, effects, and feedback mechanisms between the different "clandestine organs" and the endocrine system will provide us with a better understanding of how an organism functions, as well as reinforce the idea that there are no independent organs or systems, but a complex, interacting network of molecules, cells, tissues, signaling pathways, and mechanisms that constitute an individual. Published by Elsevier Inc.

Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society Clinical Practice Guideline.

PubMed

Hembree, Wylie C; Cohen-Kettenis, Peggy T; Gooren, Louis; Hannema, Sabine E; Meyer, Walter J; Murad, M Hassan; Rosenthal, Stephen M; Safer, Joshua D; Tangpricha, Vin; T'Sjoen, Guy G

2017-11-01

To update the "Endocrine Treatment of Transsexual Persons: An Endocrine Society Clinical Practice Guideline," published by the Endocrine Society in 2009. The participants include an Endocrine Society-appointed task force of nine experts, a methodologist, and a medical writer. This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation approach to describe the strength of recommendations and the quality of evidence. The task force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies. Group meetings, conference calls, and e-mail communications enabled consensus. Endocrine Society committees, members and cosponsoring organizations reviewed and commented on preliminary drafts of the guidelines. Gender affirmation is multidisciplinary treatment in which endocrinologists play an important role. Gender-dysphoric/gender-incongruent persons seek and/or are referred to endocrinologists to develop the physical characteristics of the affirmed gender. They require a safe and effective hormone regimen that will (1) suppress endogenous sex hormone secretion determined by the person's genetic/gonadal sex and (2) maintain sex hormone levels within the normal range for the person's affirmed gender. Hormone treatment is not recommended for prepubertal gender-dysphoric/gender-incongruent persons. Those clinicians who recommend gender-affirming endocrine treatments-appropriately trained diagnosing clinicians (required), a mental health provider for adolescents (required) and mental health professional for adults (recommended)-should be knowledgeable about the diagnostic criteria and criteria for gender-affirming treatment, have sufficient training and experience in assessing psychopathology, and be willing to participate in the ongoing care throughout the endocrine transition. We recommend treating gender

Endocrine pancreatic function changes after acute pancreatitis.

PubMed

Wu, Deqing; Xu, Yaping; Zeng, Yue; Wang, Xingpeng

2011-10-01

This study aimed to investigate the impairment of pancreatic endocrine function and the associated risk factors after acute pancreatitis (AP). Fifty-nine patients were subjected to tests of pancreatic function after an attack of pancreatitis. The mean time after the event was 3.5 years. Pancreatic endocrine function was evaluated by fasting blood glucose (FBG), glycosylated hemoglobin, fasting blood insulin, and C-peptide. Homeostasis model assessment was used to evaluate insulin resistance and islet β-cell function. Pancreatic exocrine function was evaluated by fecal elastase 1. Factors that could influence endocrine function were also investigated. Nineteen patients (32%) were found to have elevated FBG, whereas 5 (8%) had abnormal glycosylated hemoglobin levels. The levels of FBG, fasting blood insulin, and C-peptide were higher in patients than in controls (P < 0.01). The islet β-cell function of patients was lower than that of controls (P < 0.01), whereas insulin resistance index was higher among patients (P < 0.01). Obesity, hyperlipidemia, and diabetes-related symptoms were found to be associated with endocrine insufficiency. Pancreatic exocrine functional impairment was found at the same time. Endocrine functional impairment with insulin resistance was found in patients after AP. Obesity, hyperlipidemia, and diabetes-related symptoms increased the likelihood of developing functional impairment after AP.

Global expression analysis of gene regulatory pathways during endocrine pancreatic development.

PubMed

Gu, Guoqiang; Wells, James M; Dombkowski, David; Preffer, Fred; Aronow, Bruce; Melton, Douglas A

2004-01-01

To define genetic pathways that regulate development of the endocrine pancreas, we generated transcriptional profiles of enriched cells isolated from four biologically significant stages of endocrine pancreas development: endoderm before pancreas specification, early pancreatic progenitor cells, endocrine progenitor cells and adult islets of Langerhans. These analyses implicate new signaling pathways in endocrine pancreas development, and identified sets of known and novel genes that are temporally regulated, as well as genes that spatially define developing endocrine cells from their neighbors. The differential expression of several genes from each time point was verified by RT-PCR and in situ hybridization. Moreover, we present preliminary functional evidence suggesting that one transcription factor encoding gene (Myt1), which was identified in our screen, is expressed in endocrine progenitors and may regulate alpha, beta and delta cell development. In addition to identifying new genes that regulate endocrine cell fate, this global gene expression analysis has uncovered informative biological trends that occur during endocrine differentiation.

Schedule for Rating Disabilities; the Endocrine System. Final rule.

PubMed

2017-11-02

This document amends the Department of Veterans Affairs (VA) Schedule for Rating Disabilities (VASRD) by revising the portion of the Schedule that addresses endocrine conditions and disorders of the endocrine system. The effect of this action is to ensure that the VASRD uses current medical terminology and to provide detailed and updated criteria for evaluation of endocrine disorders.

Endocrine causes of nonalcoholic fatty liver disease

PubMed Central

Marino, Laura; Jornayvaz, François R

2015-01-01

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the industrialized world. The prevalence of NAFLD is increasing, becoming a substantial public health burden. NAFLD includes a broad spectrum of disorders, from simple conditions such as steatosis to severe manifestations such as fibrosis and cirrhosis. The relationship of NAFLD with metabolic alterations such as type 2 diabetes is well described and related to insulin resistance, with NAFLD being recognized as the hepatic manifestation of metabolic syndrome. However, NAFLD may also coincide with endocrine diseases such as polycystic ovary syndrome, hypothyroidism, growth hormone deficiency or hypercortisolism. It is therefore essential to remember, when discovering altered liver enzymes or hepatic steatosis on radiological exams, that endocrine diseases can cause NAFLD. Indeed, the overall prognosis of NAFLD may be modified by treatment of the underlying endocrine pathology. In this review, we will discuss endocrine diseases that can cause NALFD. Underlying pathophysiological mechanisms will be presented and specific treatments will be reviewed. PMID:26494962

Endocrine disorders and diabetes in Japan.

PubMed

Seino, Y; Imura, H

1994-10-01

The frequency of glucose intolerance including diabetes and IGT in endocrine diseases was compared between Japan and foreign countries. It was revealed that the frequency of diabetes in endocrine diseases is generally higher in Japan than in foreign countries. In addition, plasma insulin response to glucose was exaggerated in Cushing's syndrome with glucose intolerance, but was impaired in acromegaly and pheochromocytoma with glucose intolerance.

Rare and Unusual Endocrine Cancer Syndromes with Mutated Genes

PubMed Central

Lodish, Maya B.; Stratakis, Constantine A.

2010-01-01

The study of a number of rare familial syndromes associated with endocrine tumor development has led to the identification of genes involved in the development of these tumors. Major advances have been made expanding our understanding of the pathophysiology of these rare endocrine tumors, resulting in the elucidation of causative genes in rare familial diseases and a better understanding of the signaling pathways implicated in endocrine cancers. Recognition of the familial syndrome associated with a particular patient’s endocrine tumor has important implications in terms of prognosis, screening of family members, and screening for associated conditions. PMID:21167385

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.

Modulation of vergence by off-vertical yaw axis rotation in the monkey: normal characteristics and effects of space flight

NASA Technical Reports Server (NTRS)

Dai, M.; Raphan, T.; Kozlovskaya, I.; Cohen, B.

1996-01-01

Horizontal movements of both eyes were recorded simultaneously using scleral search coils in 2 rhesus monkeys before and after the COSMOS 2229 space-flight of 1992-1993. Another 9 monkeys were tested at comparable time intervals and served as controls. Ocular vergence, defined as the difference in horizontal position between the left and right eyes, was measured during off-vertical yaw axis rotation (OVAR) in darkness. Vergence was modulated sinusoidally as a function of head position with regard to gravity during OVAR. The amplitude of peak-to-peak modulation increased with increments in tilt of the angle of the rotational axis (OVAR tilt angle) that ranged from 15 degrees to 90 degrees. Of the 11 monkeys tested, 1 had no measurable modulation in vergence. In the other 10, the mean amplitude of the peak to peak modulation was 5.5 degrees +/- 1.3 degrees at 90 degrees tilt. Each of these monkeys had maximal vergence when its nose was pointed close to upward (gravity back; mean phase: -0.9 degree +/- 26 degrees). After space flight, the modulation in vergence was reduced by over 50% for the two flight monkeys, but the phase of vergence modulation was not altered. The reduction in vergence modulation was sustained for the 11-day postflight testing period. We conclude that changes in vergence are induced in monkeys by the sinusoidal component of gravity acting along the naso-occipital axis during yaw axis OVAR, and that the modulation of the vergence reflex is significantly less sensitive to linear acceleration after space flight.

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

Tributyltin: Advancing the science on assessing endocrine disruption with an unconventional endocrine-disrupting compound

USGS Publications Warehouse

Lagadic, Laurent; Katsiadaki, Ioanna; Biever, Ronald C.; Guiney, Patrick; Karouna-Renier, Natalie K.; Schwarz, Tamar; Meador, James P.

2018-01-01

Tributyltin (TBT) has been recognized as an endocrine disrupting chemical (EDC) for several decades. However, only in the last decade, was its primary endocrine mechanism of action (MeOA) elucidated—interactions with the nuclear retinoid-X receptor (RXR), peroxisome proliferator-activated receptor γ (PPARγ), and their heterodimers. This molecular initiating event (MIE) alters a range of reproductive, developmental, and metabolic pathways at the organism level. It is noteworthy that a variety of MeOAs have been proposed over the years for the observed endocrine-type effects of TBT; however, convincing data for the MIE was provided only recently and now several researchers have confirmed and refined the information on this MeOA. One of the most important lessons learned from years of research on TBT concerns apparent species sensitivity. Several aspects such as the rates of uptake and elimination, chemical potency, and metabolic capacity are all important for identifying the most sensitive species for a given chemical, including EDCs. For TBT, much of this was discovered by trial and error, hence important relationships and important sensitive taxa were not identified until several decades after its introduction to the environment. As recognized for many years, TBT-induced responses are known to occur at very low concentrations for molluscs, a fact that has more recently also been observed in fish species. This review explores the MeOA and effects of TBT in different species (aquatic molluscs and other invertebrates, fish, amphibians, birds, and mammals) according to the OECD Conceptual Framework for Endocrine Disruptor Testing and Assessment (CFEDTA). The information gathered on biological effects that are relevant for populations of aquatic animals was used to construct Species Sensitivity Distributions (SSDs) based on No Observed Effect Concentrations (NOECs) and Lowest Observed Effect Concentrations (LOECs). Fish appear at the lower end of these distributions

Tributyltin: Advancing the Science on Assessing Endocrine Disruption with an Unconventional Endocrine-Disrupting Compound.

PubMed

Lagadic, Laurent; Katsiadaki, Ioanna; Biever, Ron; Guiney, Patrick D; Karouna-Renier, Natalie; Schwarz, Tamar; Meador, James P

Tributyltin (TBT) has been recognized as an endocrine disrupting chemical (EDC) for several decades. However, only in the last decade, was its primary endocrine mechanism of action (MeOA) elucidated-interactions with the nuclear retinoid-X receptor (RXR), peroxisome proliferator-activated receptor γ (PPARγ), and their heterodimers. This molecular initiating event (MIE) alters a range of reproductive, developmental, and metabolic pathways at the organism level. It is noteworthy that a variety of MeOAs have been proposed over the years for the observed endocrine-type effects of TBT; however, convincing data for the MIE was provided only recently and now several researchers have confirmed and refined the information on this MeOA. One of the most important lessons learned from years of research on TBT concerns apparent species sensitivity. Several aspects such as the rates of uptake and elimination, chemical potency, and metabolic capacity are all important for identifying the most sensitive species for a given chemical, including EDCs. For TBT, much of this was discovered by trial and error, hence important relationships and important sensitive taxa were not identified until several decades after its introduction to the environment. As recognized for many years, TBT-induced responses are known to occur at very low concentrations for molluscs, a fact that has more recently also been observed in fish species. This review explores the MeOA and effects of TBT in different species (aquatic molluscs and other invertebrates, fish, amphibians, birds, and mammals) according to the OECD Conceptual Framework for Endocrine Disruptor Testing and Assessment (CFEDTA). The information gathered on biological effects that are relevant for populations of aquatic animals was used to construct Species Sensitivity Distributions (SSDs) based on No Observed Effect Concentrations (NOECs) and Lowest Observed Effect Concentrations (LOECs). Fish appear at the lower end of these distributions

Highlighting Indication of extracorporeal membrane oxygenation in endocrine emergencies

PubMed Central

Chao, Anne; Wang, Chih-Hsien; You, Hao-Chun; Chou, Nai-Kwoun; Yu, Hsi-Yu; Chi, Nai-Hsin; Huang, Shu-Chien; Wu, I-Hui; Tseng, Li-Jung; Lin, Ming-Hsien; Chen, Yih-Sharng

2015-01-01

Extracorporeal membrane oxygenation (ECMO) has been repeatedly used to rescue patients with cardiopulmonary arrest. However, its clinical utility in endocrine emergencies remains unclear. Herein, we describe a case series of 12 patients presenting with refractory shock secondary to endocrine emergencies who were rescued by ECMO support. Patients were identified between 2005 and 2012 from our ECMO registry. The diagnostic distribution was as follows: pheochromocytoma crisis (n = 4), thyroid storm (n = 5), and diabetic ketoacidosis (n = 3). The initial presentation of pheochromocytoma crisis was indistinguishable from acute myocardial infarction (AMI) and frequently accompanied by paroxysmal hypertension and limb ischemia. Thyroid storm was characterized by hyperbilirubinemia and severe gastrointestinal bleeding, whereas neurological symptoms were common in diabetic ketoacidosis. The clinical outcomes of patients with endocrine emergencies were compared with those of 80 cases with AMI who received ECMO because of cardiogenic shock. The cardiac function and the general conditions showed a significantly faster recovery in patients with endocrine emergencies than in those with AMI. We conclude that ECMO support can be clinically useful in endocrine emergencies. The screening of endocrine diseases should be considered during the resuscitation of patients with refractory circulatory shock. PMID:26299943

Highlighting Indication of extracorporeal membrane oxygenation in endocrine emergencies.

PubMed

Chao, Anne; Wang, Chih-Hsien; You, Hao-Chun; Chou, Nai-Kwoun; Yu, Hsi-Yu; Chi, Nai-Hsin; Huang, Shu-Chien; Wu, I-Hui; Tseng, Li-Jung; Lin, Ming-Hsien; Chen, Yih-Sharng

2015-08-24

Extracorporeal membrane oxygenation (ECMO) has been repeatedly used to rescue patients with cardiopulmonary arrest. However, its clinical utility in endocrine emergencies remains unclear. Herein, we describe a case series of 12 patients presenting with refractory shock secondary to endocrine emergencies who were rescued by ECMO support. Patients were identified between 2005 and 2012 from our ECMO registry. The diagnostic distribution was as follows: pheochromocytoma crisis (n = 4), thyroid storm (n = 5), and diabetic ketoacidosis (n = 3). The initial presentation of pheochromocytoma crisis was indistinguishable from acute myocardial infarction (AMI) and frequently accompanied by paroxysmal hypertension and limb ischemia. Thyroid storm was characterized by hyperbilirubinemia and severe gastrointestinal bleeding, whereas neurological symptoms were common in diabetic ketoacidosis. The clinical outcomes of patients with endocrine emergencies were compared with those of 80 cases with AMI who received ECMO because of cardiogenic shock. The cardiac function and the general conditions showed a significantly faster recovery in patients with endocrine emergencies than in those with AMI. We conclude that ECMO support can be clinically useful in endocrine emergencies. The screening of endocrine diseases should be considered during the resuscitation of patients with refractory circulatory shock.

Repeated thermal stressor causes chronic elevation of baseline corticosterone and suppresses the physiological endocrine sensitivity to acute stressor in the cane toad (Rhinella marina).

PubMed

Narayan, Edward J; Hero, Jean-Marc

2014-04-01

Extreme environmental temperature could impact the physiology and ecology of animals. The stress endocrine axis provides necessary physiological stress response to acute (day-day) stressors. Presently, there are no empirical evidences showing that exposure to extreme thermal stressor could cause chronic stress in amphibians. This could also modulate the physiological endocrine sensitivity to acute stressors and have serious implications for stress coping in amphibians, particularly those living in fragmented and disease prone environments. We addressed this important question using the cane toad (Rhinella marina) model from its introduced range in Queensland, Australia. We quantified their physiological endocrine sensitivity to a standard acute (capture and handling) stressor after exposing the cane toads to thermal shock at 35°C for 30min daily for 34 days. Corticosterone (CORT) responses to the capture and handling protocol were measured on three sampling intervals (days 14, 24, and 34) to determine whether the physiological endocrine sensitivity was maintained or modulated over-time. Two control groups (C1 for baseline CORT measurement only and C2 acute handled only) and two temperature treatment groups (T1 received daily thermal shock up to day 14 only and a recovery phase of 20 days and T2 received thermal shock daily for 34 days). Results showed that baseline CORT levels remained high on day 14 (combined effect of capture, captivity and thermal stress) for both T1 and T2. Furthermore, baseline CORT levels decreased for T1 once the thermal shock was removed after day 14 and returned to baseline by day 29. On the contrary, baseline CORT levels kept on increasing for T2 over the 34 days of daily thermal shocks. Furthermore, the magnitudes of the acute CORT responses or physiological endocrine sensitivity were consistently high for both C1 and T1. However, acute CORT responses for T2 toads were dramatically reduced between days 24 and 34. These novel findings

Appetite-Controlling Endocrine Systems in Teleosts

PubMed Central

Rønnestad, Ivar; Gomes, Ana S.; Murashita, Koji; Angotzi, Rita; Jönsson, Elisabeth; Volkoff, Hélène

2017-01-01

Mammalian studies have shaped our understanding of the endocrine control of appetite and body weight in vertebrates and provided the basic vertebrate model that involves central (brain) and peripheral signaling pathways as well as environmental cues. The hypothalamus has a crucial function in the control of food intake, but other parts of the brain are also involved. The description of a range of key neuropeptides and hormones as well as more details of their specific roles in appetite control continues to be in progress. Endocrine signals are based on hormones that can be divided into two groups: those that induce (orexigenic), and those that inhibit (anorexigenic) appetite and food consumption. Peripheral signals originate in the gastrointestinal tract, liver, adipose tissue, and other tissues and reach the hypothalamus through both endocrine and neuroendocrine actions. While many mammalian-like endocrine appetite-controlling networks and mechanisms have been described for some key model teleosts, mainly zebrafish and goldfish, very little knowledge exists on these systems in fishes as a group. Fishes represent over 30,000 species, and there is a large variability in their ecological niches and habitats as well as life history adaptations, transitions between life stages and feeding behaviors. In the context of food intake and appetite control, common adaptations to extended periods of starvation or periods of abundant food availability are of particular interest. This review summarizes the recent findings on endocrine appetite-controlling systems in fish, highlights their impact on growth and survival, and discusses the perspectives in this research field to shed light on the intriguing adaptations that exist in fish and their underlying mechanisms. PMID:28458653

IDENTIFYING ENDOCRINE DISRUPTORS BY HIGH-RESOLUTION MASS SPECTROMETRY

EPA Science Inventory

The EPA is currently interested in human and ecosystem exposure to endocrine disruptors (1)-compounds that interfere with endogenous hormone systems. Possible endocrine disruptors in the environment include certain pesticides, industrial by-products, and pharmaceuticals. Such c...

Squamous cell carcinoma of the oral cavity and oropharynx in patients aged 18-45 years: A case-control study to evaluate the risk factors with emphasis on stress, diet, oral hygiene, and family history.

PubMed

Dholam, K P; Chouksey, G C

2016-01-01

Increasing incidence of squamous cell carcinoma (SCC) of the oral cavity and oropharynx is reported in young adults. However, there is a paucity regarding etiology and risk factors. To evaluate the exposure potential carcinogenic factors among a sample aged 45 years and younger, diagnosed with SCC of the oral cavity and oropharynx. Eighty-five case samples aged 18-45 years, diagnosed with SCC of the oral cavity and oropharynx were compared with 85 controls who had never had cancer, matched for age and sex. This study was conducted by questionnaire-based interviews. Questionnaire contained items about exposure to the following risk factors: Caries prevalence, oral hygiene status, dental trauma, dental visit, stress, family history of cancer, environmental exposure to potential carcinogens, diet, body mass index (BMI), habits such as smoking, tobacco chewing, betel quid/pan, or supari. Odds ratios (ORs) of oral and pharyngeal cancer and the corresponding 95% confidence intervals were estimated using multiple logistic regression models. P< 0.05 was considered statistically significant. Elevated OR was seen in young adults who had poor oral hygiene, stress, dental trauma, low BMI, family history of cancer, exposure to environmental carcinogens, and habit of placement of quid for 11-20 years. An increased risk of oral and pharyngeal cancer was seen in cases who had poor oral hygiene, stress, dental trauma, low BMI, family history of cancer, exposure to environmental carcinogens, and habit of placement of quid.

Assessment of Surgical Learning Curves in Transoral Robotic Surgery for Squamous Cell Carcinoma of the Oropharynx

PubMed Central

Albergotti, William G.; Gooding, William E.; Kubik, Mark W.; Geltzeiler, Mathew; Kim, Seungwon; Duvvuri, Umamaheswar; Ferris, Robert L.

2017-01-01

IMPORTANCE Transoral robotic surgery (TORS) is increasingly employed as a treatment option for squamous cell carcinoma of the oropharynx (OPSCC). Measures of surgical learning curves are needed particularly as clinical trials using this technology continue to evolve. OBJECTIVE To assess learning curves for the oncologic TORS surgeon and to identify the number of cases needed to identify the learning phase. DESIGN, SETTING, AND PARTICIPANTS A retrospective review of all patients who underwent TORS for OPSCC at the University of Pittsburgh Medical Center between March 2010 and March 2016. Cases were excluded for involvement of a subsite outside of the oropharynx, for nonmalignant abnormality or nonsquamous histology, unknown primary, no tumor in the main specimen, free flap reconstruction, and for an inability to define margin status. EXPOSURES Transoral robotic surgery for OPSCC. MAIN OUTCOMES AND MEASURES Primary learning measures defined by the authors include the initial and final margin status and time to resection of main surgical specimen. A cumulative sum learning curve was developed for each surgeon for each of the study variables. The inflection point of each surgeon’s curve was considered to be the point signaling the completion of the learning phase. RESULTS There were 382 transoral robotic procedures identified. Of 382 cases, 160 met our inclusion criteria: 68 for surgeon A, 37 for surgeon B, and 55 for surgeon C. Of the 160 included patients, 125 were men and 35 were women. The mean (SD) age of participants was 59.4 (9.5) years. Mean (SD) time to resection including robot set-up was 79 (36) minutes. The inflection points for the final margin status learning curves were 27 cases (surgeon A) and 25 cases (surgeon C). There was no inflection point for surgeon B for final margin status. Inflection points for mean time to resection were: 39 cases (surgeon A), 30 cases (surgeon B), and 27 cases (surgeon C). CONCLUSIONS AND RELEVANCE Using metrics of

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)

From endocrine to rheumatism: do gut hormones play roles in rheumatoid arthritis?

PubMed

Chen, Chih-Yen; Tsai, Chang-Youh

2014-02-01

RA is characterized by chronic inflammation in the musculoskeletal system, in which TNF-α is the key cytokine trigger. TNF-α, previously known as cachectin, is implicated in the modulation of body composition and energy expenditure. Gut hormones, including acyl ghrelin, des-acyl ghrelin, GIP, GLP-1 and PYY, have been known to be the major regulators of appetite, nutrition, energy expenditure and body mass formation. Emerging evidence indicates that blockade of TNF-α by biologics not only ameliorates rheumatoid inflammation, but can affect the secretion and action of gut hormones on appetite, body composition, energy expenditure, muscle catabolism and bone remodelling. A link between the gastrointestinal endocrine axis and the immune system may be established through the interaction of proinflammatory cytokines, including TNF-α and these gut hormones. With the ever-increasing understanding of rheumatoid inflammation and the invention of more biologics to modulate the cytokine network, more attention should be given to the possible immunomodulatory roles of gut hormones in autoimmune inflammatory reactions.

Research on Endocrine Disruptors

EPA Pesticide Factsheets

EPA researchers are developing innovative approaches, tools, models and data to improve the understanding of potential risks to human health and wildlife from chemicals that could disrupt the endocrine system.

Endocrine Profiling and Prioritization Using ToxCast Assays

EPA Science Inventory

The U.S. EPA's Endocrine Disruptor Screening Program (EDSP) is charged with screening pesticide chemicals and environmental contaminants for their potential to affect the endocrine systems of humans and wildlife (http://www.epa.gov/endo/). The prioritization of chemicals for test...

Controversial endocrine interventions for the aged.

PubMed

Leow, M K S; Loh, K C

2006-07-01

Specific endocrine changes occur with the ageing process. The last decade has witnessed significant progress in the basic and clinical science of ageing, thereby rejuvenating the interest in anti-ageing medicine, especially that of hormone replacement, by medical professionals and the lay public. However, endocrine manipulation as a therapeutic strategy for ageing is still evolving as continuing research attempts to answer the many questions of what it can achieve at the risk of incurring unknown long-term adverse effects. The current day doctor is confronted with a host of options, and will benefit from a synopsis of the latest evidence before making the most appropriate decision for aged patients seeking hormonal replacement therapy as a means to counter the effects of ageing. This review aims to give a rapid overview of the endocrine profile of geriatric population and the studies on the more controversial hormonal replacement therapies for the aged.

Sentinel node localization in oral cavity and oropharynx squamous cell cancer.

PubMed

Taylor, R J; Wahl, R L; Sharma, P K; Bradford, C R; Terrell, J E; Teknos, T N; Heard, E M; Wolf, G T; Chepeha, D B

2001-08-01

To evaluate the feasibility and predictive ability of the sentinel node localization technique for patients with squamous cell carcinoma of the oral cavity or oropharynx and clinically negative necks. Prospective, efficacy study comparing the histopathologic status of the sentinel node with that of the remaining neck dissection specimen. Tertiary referral center. Patients with T1 or T2 disease and clinically negative necks were eligible for the study. Nine previously untreated patients with oral cavity or oropharyngeal squamous cell carcinoma were enrolled in the study. Unfiltered technetium Tc 99m sulfur colloid injections of the primary tumor and lymphoscintigraphy were performed on the day before surgery. Intraoperatively, the sentinel node(s) was localized with a gamma probe and removed after tumor resection and before neck dissection. The primary outcome was the negative predictive value of the histopathologic status of the sentinel node for predicting cervical metastases. Sentinel nodes were identified in 9 previously untreated patients. In 5 patients, there were no positive nodes. In 4 patients, the sentinel nodes were the only histopathologically positive nodes. In previously untreated patients, the sentinel node technique had a negative predictive value of 100% for cervical metastasis. Our preliminary investigation shows that sentinel node localization is technically feasible in head and neck surgery and is predictive of cervical metastasis. The sentinel node technique has the potential to decrease the number of neck dissections performed in clinically negative necks, thus reducing the associated morbidity for patients in this group.

Ipsilateral irradiation for well lateralized carcinomas of the oral cavity and oropharynx: results on tumor control and xerostomia

PubMed Central

Cerezo, Laura; Martín, Margarita; López, Mario; Marín, Alicia; Gómez, Alberto

2009-01-01

Background In head and neck cancer, bilateral neck irradiation is the standard approach for many tumor locations and stages. Increasing knowledge on the pattern of nodal invasion leads to more precise targeting and normal tissue sparing. The aim of the present study was to evaluate the morbidity and tumor control for patients with well lateralized squamous cell carcinomas of the oral cavity and oropharynx treated with ipsilateral radiotherapy. Methods Twenty consecutive patients with lateralized carcinomas of the oral cavity and oropharynx were treated with a prospective management approach using ipsilateral irradiation between 2000 and 2007. This included 8 radical oropharyngeal and 12 postoperative oral cavity carcinomas, with Stage T1-T2, N0-N2b disease. The actuarial freedom from contralateral nodal recurrence was determined. Late xerostomia was evaluated using the European Organization for Research and Treatment of Cancer QLQ-H&N35 questionnaire and the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 3. Results At a median follow-up of 58 months, five-year overall survival and loco-regional control rates were 82.5% and 100%, respectively. No local or contralateral nodal recurrences were observed. Mean dose to the contralateral parotid gland was 4.72 Gy and to the contralateral submandibular gland was 15.30 Gy. Mean score for dry mouth was 28.1 on the 0-100 QLQ-H&N35 scale. According to CTCAE v3 scale, 87.5% of patients had grade 0-1 and 12.5% grade 2 subjective xerostomia. The unstimulated salivary flow was > 0.2 ml/min in 81.2% of patients and 0.1-0.2 ml/min in 19%. None of the patients showed grade 3 xerostomia. Conclusion In selected patients with early and moderate stages, well lateralized oral and oropharyngeal carcinomas, ipsilateral irradiation treatment of the primary site and ipsilateral neck spares salivary gland function without compromising loco-regional control. PMID:19723329

Overview of air pollution and endocrine disorders

PubMed Central

Darbre, Philippa D

2018-01-01

Over recent years, many environmental pollutant chemicals have been shown to possess the ability to interfere in the functioning of the endocrine system and have been termed endocrine disrupting chemicals (EDCs). These compounds exist in air as volatile or semi-volatile compounds in the gas phase or attached to particulate matter. They include components of plastics (phthalates, bisphenol A), components of consumer goods (parabens, triclosan, alkylphenols, fragrance compounds, organobromine flame retardants, fluorosurfactants), industrial chemicals (polychlorinated biphenyls), products of combustion (polychlorinated dibenzodioxins/furans, polyaromatic hydrocarbons), pesticides, herbicides, and some metals. This review summarizes current knowledge concerning the sources of EDCs in air, measurements of levels of EDCs in air, and the potential for adverse effects of EDCs in air on human endocrine health. PMID:29872334

Endocrine Disruptor Screening Program (EDSP) 1998 Federal Register Notices

EPA Pesticide Factsheets

EPA outlined the Endocrine Disruptor Screening Program (EDSP), which incorporated many of the Endocrine Disruptor Screening and Testing Advisory Committee's (EDSTAC) recommendations, in two Federal Register Notices published in 1998.

Tumors of the endocrine/neuroendocrine system: an overview.

PubMed

Erlandson, R A; Nesland, J M

1994-01-01

For the sake of discussion, the markedly diversified tumors of the endocrine/neuroendocrine system are classified as those originating in classic epithelial endocrine organs (eg, adrenal cortical adenomas), from the diffuse endocrine cells (eg, jejunal carcinoid tumors), or from clusters of these cells (eg, islet cell tumors); and those arising from neurosecretory neurons (eg, neuroblastoma) or paraganglia (eg, carotid body tumor). Although traditional transmission electron microscopy is useful for identifying neurosecretory or endosecretory granules as such, with few exceptions (eg, insulin-containing granules with a complex paracrystalline core) it is not possible to ascribe a granule type (size, shape, or ultrastructure) to a distinct nosologic entity or secretory product because of their overlapping fine structures in different cell types. Immunoelectron microscopy methods utilizing colloidal gold-labeled secondary antibodies can be used to localize virtually any antigen (peptide or neuroamine) to a specific neurosecretory or endosecretory granule or other cell structure. General endocrine/neuroendocrine cell markers such as neuron-specific enolase, the chromogranins, and synaptophysin are useful in identifying neuroendocrine differentiation in a neoplasm using routine immunohistochemical procedures. The current relevance of the APUD concept of Pearse as well as the biologic importance of endocrine/neuroendocrine secretory products such as bombesin and insulinlike growth factors also are discussed.

Unmasking the truth behind endocrine disruptors.

PubMed

DiDiego, Michele Lamse; Eggert, Julia A; Pruitt, Rosanne H; Larcom, Lyndon L

2005-10-01

The increase in reproductive cancers and developmental problems over the past 70 years has led researchers to suspect environmental influences as a root cause. Evidence from wildlife and laboratory studies suggests that exposure to endocrine disruptors (EnDs) may be the cause. An EnD is a foreign substance or mixture that alters the function of the endocrine system. They can be found in food, water, soil, or air. Research into their possible role provides an opportunity to decrease modifiable risk factors.

[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.

Endocrine Aspects of Environmental “Obesogen” Pollutants

PubMed Central

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

Parabens and their effects on the endocrine system.

PubMed

Nowak, Karolina; Ratajczak-Wrona, Wioletta; Górska, Maria; Jabłońska, Ewa

2018-03-27

Preservatives (ingredients which inhibit growth of microorganisms) are used to prolong shelf life of various foods, cosmetics, and pharmaceutical products. Parabens are one of the most popular preservatives used in the aforementioned products and is currently being used worldwide. Parabens are easily absorbed by the human body. Thus, it is important to discuss about their safety with respect to human physiology. In view of the current literature, which classifies parabens as a group of endocrine disrupting chemicals (EDCs), it seems that the precise assessment of their influence on the human endocrine system is particularly important. Disruption of the endocrine homoeostasis might lead to multidirectional implications causing disruption of fitness and functions of the body. Therefore, in this review article, we aimed to summarize the current literature on properties, occurrence, and metabolism of parabens as well as to present recent progress in knowledge about their influence on the human endocrine system. Copyright © 2018 Elsevier B.V. All rights reserved.

The fish in the turtle: on the functionality of the oropharynx in the common musk turtle Sternotherus odoratus (Chelonia, Kinosternidae) concerning feeding and underwater respiration.

PubMed

Heiss, Egon; Natchev, Nikolay; Beisser, Christian; Lemell, Patrick; Weisgram, Josef

2010-08-01

In tetrapods, the oropharyngeal cavity and its anatomical structures are mainly, but not exclusively, responsible for the uptake and intraoral transport of food. In this study, we provide structural evidence for a second function of the oropharynx in the North American common musk turtle, Sternotherus odoratus, Kinosternidae: aquatic gas exchange. Using high-speed video, we demonstrate that S. odoratus can grasp food on land by its jaws, but is afterward incapable of lingual based intraoral transport; food is always lost during such an attempt. Scanning electron microscopy and light microscopy reveal that the reason for this is a poorly developed tongue. Although small, the tongue bears a variety of lobe-like papillae, which might be misinterpreted as an adaptation for terrestrial food uptake. Similar papillae also cover most of the oropharynx. They are highly vascularized as shown by light microscopy and may play an important role in aquatic gas exchange. The vascularization of the oropharyngeal papillae in S. odoratus is then compared with that in Emys orbicularis, an aquatic emydid with similar ecology but lacking the ability of underwater respiration. Oropharyngeal papillae responsible for aquatic respiration are also found in soft-shelled turtles (Trionychidae), the putative sister group of the kinosternids. This trait could therefore represent a shared, ancestral character of both groups involving advantages in the aquatic environment they inhabit. (c) 2010 Wiley-Liss, Inc.

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. Copyright © 2016 Elsevier Inc. All rights reserved.

Training our Future Endocrine Surgeons: A Look at the Endocrine Surgery Operative Experience of U.S. Surgical Residents

PubMed Central

Zarebczan, Barbara; Rajamanickam, Victoria; Leverson, Glen; Chen, Herbert; Sippel, Rebecca S

2010-01-01

Background Over the last 10 years the number of endocrine procedures performed in the US has increased significantly. We sought to determine if this has translated into an increase in operative volume for general surgery and otolaryngology residents. Method We evaluated records from the Resident Statistic Summaries of the RRC for US general surgery and otolaryngology residents for the years 2004-2008, specifically examining data on thyroidectomies and parathyroidectomies. Results Between 2004 and 2008, the average endocrine case volume of US general surgery and otolaryngology residents increased by approximately 15%, but otolaryngology residents performed over twice as many operations as US general surgery residents. The growth in case volume was mostly due to increases in the number of thyroidectomies performed by US general surgery and otolaryngology residents (17.9 to 21.8, p=0.007 and 46.5 to 54.4, p=0.04). Overall, otolaryngology residents also performed more parathyroidectomies than their general surgery counterparts (11.6 vs. 8.8, p=0.007). Conclusion Although there has been an increase in the number of endocrine cases performed by graduating US general surgery residents, this is significantly smaller than that of otolaryngology residents. In order to remain competitive, general surgery residents wishing to practice endocrine surgery may need to pursue additional fellowship training. PMID:21134536

Diagnosis and treatment of endocrine comorbidities in patients with cystic fibrosis.

PubMed

Siwamogsatham, Oranan; Alvarez, Jessica A; Tangpricha, Vin

2014-10-01

The aim of this review is to provide an update on various relevant endocrine aspects of care in adolescents and adults with cystic fibrosis. As life expectancy in cystic fibrosis has continuously improved, endocrine complications have become more apparent. The common endocrine complications include cystic fibrosis related diabetes, cystic fibrosis related bone disease, vitamin D deficiency and poor growth and pubertal development. Thyroid and adrenal disorders have also been reported, although the prevalence appears to be less common. Endocrine diseases are an increasingly recognized complication that has a significant impact on the overall health of individuals with cystic fibrosis. This review summarizes the updated screening and management of endocrine diseases in the cystic fibrosis population.

EDC-2: The Endocrine Society's Second Scientific Statement on Endocrine-Disrupting Chemicals

PubMed Central

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

2015-01-01

The Endocrine Society's first Scientific Statement in 2009 provided a wake-up call to the scientific community about how environmental endocrine-disrupting chemicals (EDCs) affect health and disease. Five years later, a substantially larger body of literature has solidified our understanding of plausible mechanisms underlying EDC actions and how exposures in animals and humans—especially during development—may lay the foundations for disease later in life. At this point in history, we have much stronger knowledge about how EDCs alter gene-environment interactions via physiological, cellular, molecular, and epigenetic changes, thereby producing effects in exposed individuals as well as their descendants. Causal links between exposure and manifestation of disease are substantiated by experimental animal models and are consistent with correlative epidemiological data in humans. There are several caveats because differences in how experimental animal work is conducted can lead to difficulties in drawing broad conclusions, and we must continue to be cautious about inferring causality in humans. In this second Scientific Statement, we reviewed the literature on a subset of topics for which the translational evidence is strongest: 1) obesity and diabetes; 2) female reproduction; 3) male reproduction; 4) hormone-sensitive cancers in females; 5) prostate; 6) thyroid; and 7) neurodevelopment and neuroendocrine systems. Our inclusion criteria for studies were those conducted predominantly in the past 5 years deemed to be of high quality based on appropriate negative and positive control groups or populations, adequate sample size and experimental design, and mammalian animal studies with exposure levels in a range that was relevant to humans. We also focused on studies using the developmental origins of health and disease model. No report was excluded based on a positive or negative effect of the EDC exposure. The bulk of the results across the board strengthen the

A review on endocrine disruptors and their possible impacts on human health.

PubMed

Kabir, Eva Rahman; Rahman, Monica Sharfin; Rahman, Imon

2015-07-01

Endocrine disruption is a named field of research which has been very active for over 10 years, although the effects of endocrine disruptors in wildlife have been studied mainly in vast since the 1940s. A large number of chemicals have been identified as endocrine disruptors and humans can be exposed to them either due to their occupations or through dietary and environmental exposure (water, soil and air). Endocrine disrupting chemicals are compounds that alter the normal functioning of the endocrine system of both humans and wildlife. In order to understand the vulnerability and risk factors of people due to endocrine disruptors as well as the remedies for these, methods need to be developed in order to predict effects on populations and communities from the knowledge of effects on individuals. For several years there have been a growing interest on the mechanism and effect of endocrine disruptors and their relation with environment and human health effect. This paper, based on extensive literature survey, briefly studies the progress mainly in human to provide information concerning causative substances, mechanism of action, ubiquity of effects and important issues related to endocrine disruptors. It also reviews the current knowledge of the potential impacts of endocrine disruptors on human health so that the effects can be known and remedies applied for the problem as soon as possible. Copyright © 2015 Elsevier B.V. All rights reserved.

A differential diagnosis of inherited endocrine tumors and their tumor counterparts

PubMed Central

Toledo, Sergio P. A.; Lourenço, Delmar M.; Toledo, Rodrigo A.

2013-01-01

Inherited endocrine tumors have been increasingly recognized in clinical practice, although some difficulties still exist in differentiating these conditions from their sporadic endocrine tumor counterparts. Here, we list the 12 main topics that could add helpful information and clues for performing an early differential diagnosis to distinguish between these conditions. The early diagnosis of patients with inherited endocrine tumors may be performed either clinically or by mutation analysis in at-risk individuals. Early detection usually has a large impact in tumor management, allowing preventive clinical or surgical therapy in most cases. Advice for the clinical and surgical management of inherited endocrine tumors is also discussed. In addition, recent clinical and genetic advances for 17 different forms of inherited endocrine tumors are briefly reviewed. PMID:23917672

A kidney-specific genetic control module in mice governs endocrine regulation of the cytochrome P450 gene Cyp27b1 essential for vitamin D3 activation.

PubMed

Meyer, Mark B; Benkusky, Nancy A; Kaufmann, Martin; Lee, Seong Min; Onal, Melda; Jones, Glenville; Pike, J Wesley

2017-10-20

The vitamin D endocrine system regulates mineral homeostasis through its activities in the intestine, kidney, and bone. Terminal activation of vitamin D 3 to its hormonal form, 1α,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ), occurs in the kidney via the cytochrome P450 enzyme CYP27B1. Despite its importance in vitamin D metabolism, the molecular mechanisms underlying the regulation of the gene for this enzyme, Cyp27b1 , are unknown. Here, we identified a kidney-specific control module governed by a renal cell-specific chromatin structure located distal to Cyp27b1 that mediates unique basal and parathyroid hormone (PTH)-, fibroblast growth factor 23 (FGF23)-, and 1,25(OH) 2 D 3 -mediated regulation of Cyp27b1 expression. Selective genomic deletion of key components within this module in mice resulted in loss of either PTH induction or FGF23 and 1,25(OH) 2 D 3 suppression of Cyp27b1 gene expression; the former loss caused a debilitating skeletal phenotype, whereas the latter conferred a quasi-normal bone mineral phenotype through compensatory homeostatic mechanisms involving Cyp24a1 We found that Cyp27b1 is also expressed at low levels in non-renal cells, in which transcription was modulated exclusively by inflammatory factors via a process that was unaffected by deletion of the kidney-specific module. These results reveal that differential regulation of Cyp27b1 expression represents a mechanism whereby 1,25(OH) 2 D 3 can fulfill separate functional roles, first in the kidney to control mineral homeostasis and second in extra-renal cells to regulate target genes linked to specific biological responses. Furthermore, we conclude that these mouse models open new avenues for the study of vitamin D metabolism and its involvement in therapeutic strategies for human health and disease. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

A kidney-specific genetic control module in mice governs endocrine regulation of the cytochrome P450 gene Cyp27b1 essential for vitamin D3 activation

PubMed Central

Meyer, Mark B.; Benkusky, Nancy A.; Kaufmann, Martin; Lee, Seong Min; Onal, Melda; Jones, Glenville; Pike, J. Wesley

2017-01-01

The vitamin D endocrine system regulates mineral homeostasis through its activities in the intestine, kidney, and bone. Terminal activation of vitamin D3 to its hormonal form, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), occurs in the kidney via the cytochrome P450 enzyme CYP27B1. Despite its importance in vitamin D metabolism, the molecular mechanisms underlying the regulation of the gene for this enzyme, Cyp27b1, are unknown. Here, we identified a kidney-specific control module governed by a renal cell-specific chromatin structure located distal to Cyp27b1 that mediates unique basal and parathyroid hormone (PTH)-, fibroblast growth factor 23 (FGF23)-, and 1,25(OH)2D3-mediated regulation of Cyp27b1 expression. Selective genomic deletion of key components within this module in mice resulted in loss of either PTH induction or FGF23 and 1,25(OH)2D3 suppression of Cyp27b1 gene expression; the former loss caused a debilitating skeletal phenotype, whereas the latter conferred a quasi-normal bone mineral phenotype through compensatory homeostatic mechanisms involving Cyp24a1. We found that Cyp27b1 is also expressed at low levels in non-renal cells, in which transcription was modulated exclusively by inflammatory factors via a process that was unaffected by deletion of the kidney-specific module. These results reveal that differential regulation of Cyp27b1 expression represents a mechanism whereby 1,25(OH)2D3 can fulfill separate functional roles, first in the kidney to control mineral homeostasis and second in extra-renal cells to regulate target genes linked to specific biological responses. Furthermore, we conclude that these mouse models open new avenues for the study of vitamin D metabolism and its involvement in therapeutic strategies for human health and disease. PMID:28808057

Immunologic Endocrine Disorders

PubMed Central

Michels, Aaron W.; Eisenbarth, George S.

2010-01-01

Autoimmunity affects multiple glands in the endocrine system. Animal models and human studies highlight the importance of alleles in HLA (human leukocyte antigen)-like molecules determining tissue specific targeting that with the loss of tolerance leads to organ specific autoimmunity. Disorders such as type 1A diabetes, Grave's disease, Hashimoto's thyroiditis, Addison's disease, and many others result from autoimmune mediated tissue destruction. Each of these disorders can be divided into stages beginning with genetic susceptibility, environmental triggers, active autoimmunity, and finally metabolic derangements with overt symptoms of disease. With an increased understanding of the immunogenetics and immunopathogenesis of endocrine autoimmune disorders, immunotherapies are becoming prevalent, especially in type 1A diabetes. Immunotherapies are being used more in multiple subspecialty fields to halt disease progression. While therapies for autoimmune disorders stop the progress of an immune response, immunomodulatory therapies for cancer and chronic infections can also provoke an unwanted immune response. As a result, there are now iatrogenic autoimmune disorders arising from the treatment of chronic viral infections and malignancies. PMID:20176260

Dermatologic manifestations of endocrine disorders

PubMed Central

Lause, Michael; Kamboj, Alisha

2017-01-01

The skin serves as a window for clinicians to understand, diagnose, and monitor endocrine disease. Dermatologic manifestations of endocrinopathies contribute significantly to an individual’s health and quality of life. In this review, we outline various disorders of the hypothalamic-pituitary axis, thyroid gland, pancreas, adrenal gland, and androgen axis as well as hereditary endocrine syndromes. In acromegaly, glycosaminoglycan deposition contributes to a thickening of skin and soft tissue, which manifests as coarsening and enlargement of facial and acral structures. Stimulation of the thyrotropin receptor in hyperthyroidism results in mesenchymal tissue proliferation and consequent pretibial myxedema; other associated cutaneous features include onycholysis, and hyperhidrosis. Individuals with hypothyroidism exhibit cold, dry skin and brittle hair as well as a jaundice-like appearance due to carotene excess. The cutaneous features of diabetes mellitus (DM), mediated to a large extent by hyperglycemia and hyperinsulinemia, include necrobiosis lipoidica diabeticorum (NLD), diabetic dermopathy, and acanthosis nigricans. Pediatric patients with Cushing’s syndrome almost invariably present with truncal obesity and growth retardation; disruption of collagen formation and the catabolic effects of hypercortisolism result in skin atrophy and purple abdominal striae. In patients with Addison’s disease, generalized hyperpigmentation, secondary to elevated levels of melanocyte-stimulating hormone (MSH), is most prominent in sun-exposed areas. Due to hyperandrogenism, individuals with polycystic ovarian syndrome (PCOS) often exhibit hirsutism, acne vulgaris, and androgenetic alopecia. In multiple endocrine neoplasia (MEN) syndromes, specific gene mutations may lead to angiofibromas, lichen amyloidosis, and ganglioneuromas. Disruptions of immune regulation result in autoimmune polyglandular syndromes (APS) and associated clinical features including chronic mucocutaneous

Immunohistochemical study on gastrointestinal endocrine cells of four reptiles

PubMed Central

Huang, Xu-Gen; Wu, Xiao-Bing

2005-01-01

AIM: To clarify the types, regional distributions and distribution densities as well as morphological features of gastrointestinal (GI) endocrine cells in various parts of the gastrointestinal track (GIT) of four reptiles, Gekko japonicus, Eumeces chinensis, Sphenomorphus indicus and Eumeces elegans. METHODS: Paraffin-embedded sections (5 μm) of seven parts (cardia, fundus, pylorus, duodenum, jejunum, ileum, rectum) of GIT dissected from the four reptiles were prepared. GI endocrine cells were revealed by using immunohistochemical techniques of streptavidin-peroxidase (S-P) method. Seven types of antisera against 5-hydroxy-tryptamine (5-HT), somatostatin (SS), gastrin (GAS), glucagon (GLU), substance P (SP), insulin and pancreatic polypeptide were identified and then GI endocrine cells were photomicrographed and counted. RESULTS: The GI endocrine system of four reptiles was a complex structure containing many endocrine cell types similar in morphology to those found in higher vertebrates. Five types of GI endocrine cells, namely 5-HT, SS, GAS, SP and GLU immunoreactive (IR) cells were identified in the GIT of G. japonicus, E. chinensis and S. indicus; while in the GIT of E. elegans only the former three types of endocrine cells were observed. No PP- and INS- IR cells were found in all four reptiles. 5-HT-IR cells, which were most commonly found in the pylorus or duodenum, distributed throughout the whole GIT of four reptiles. However, their distribution patterns varied from each other. SS-IR cells, which were mainly found in the stomach especially in the pylorus and/or fundus, were demonstrated in the whole GIT of E. chinensis, only showed restricted distribution in the other three species. GAS-IR cells, with a much restricted distribution, were mainly demonstrated in the pylorus and/or the proximal small intestine of four reptiles. GLU-IR cells exhibited a limited and species-dependent variant distribution in the GIT of four reptiles. SP-IR cells were found

Update of Endocrine Dysfunction following Pediatric Traumatic Brain Injury.

PubMed

Reifschneider, Kent; Auble, Bethany A; Rose, Susan R

2015-07-31

Traumatic brain injuries (TBI) are common occurrences in childhood, often resulting in long term, life altering consequences. Research into endocrine sequelae following injury has gained attention; however, there are few studies in children. This paper reviews the pathophysiology and current literature documenting risk for endocrine dysfunction in children suffering from TBI. Primary injury following TBI often results in disruption of the hypothalamic-pituitary-adrenal axis and antidiuretic hormone production and release, with implications for both acute management and survival. Secondary injuries, occurring hours to weeks after TBI, result in both temporary and permanent alterations in pituitary function. At five years after moderate to severe TBI, nearly 30% of children suffer from hypopituitarism. Growth hormone deficiency and disturbances in puberty are the most common; however, any part of the hypothalamic-pituitary axis can be affected. In addition, endocrine abnormalities can improve or worsen with time, having a significant impact on children's quality of life both acutely and chronically. Since primary and secondary injuries from TBI commonly result in transient or permanent hypopituitarism, we conclude that survivors should undergo serial screening for possible endocrine disturbances. High indices of suspicion for life threatening endocrine deficiencies should be maintained during acute care. Additionally, survivors of TBI should undergo endocrine surveillance by 6-12 months after injury, and then yearly, to ensure early detection of deficiencies in hormonal production that can substantially influence growth, puberty and quality of life.

Update of Endocrine Dysfunction following Pediatric Traumatic Brain Injury

PubMed Central

Reifschneider, Kent; Auble, Bethany A.; Rose, Susan R.

2015-01-01

Traumatic brain injuries (TBI) are common occurrences in childhood, often resulting in long term, life altering consequences. Research into endocrine sequelae following injury has gained attention; however, there are few studies in children. This paper reviews the pathophysiology and current literature documenting risk for endocrine dysfunction in children suffering from TBI. Primary injury following TBI often results in disruption of the hypothalamic-pituitary-adrenal axis and antidiuretic hormone production and release, with implications for both acute management and survival. Secondary injuries, occurring hours to weeks after TBI, result in both temporary and permanent alterations in pituitary function. At five years after moderate to severe TBI, nearly 30% of children suffer from hypopituitarism. Growth hormone deficiency and disturbances in puberty are the most common; however, any part of the hypothalamic-pituitary axis can be affected. In addition, endocrine abnormalities can improve or worsen with time, having a significant impact on children’s quality of life both acutely and chronically. Since primary and secondary injuries from TBI commonly result in transient or permanent hypopituitarism, we conclude that survivors should undergo serial screening for possible endocrine disturbances. High indices of suspicion for life threatening endocrine deficiencies should be maintained during acute care. Additionally, survivors of TBI should undergo endocrine surveillance by 6–12 months after injury, and then yearly, to ensure early detection of deficiencies in hormonal production that can substantially influence growth, puberty and quality of life. PMID:26287247

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.

Endocrine actions of vitamin D in skin: Relevance for photocarcinogenesis of non-melanoma skin cancer, and beyond.

PubMed

Reichrath, Jörg; Saternus, Roman; Vogt, Thomas

2017-09-15

The skin represents a pivotal organ for the human body's vitamin D endocrine system, being both the site of ultraviolet (UV)-B-induced vitamin D synthesis and a target tissue for the pluripotent effects of 1,25(OH) 2 D 3 and other biologically active vitamin D metabolites. As many other steroid hormones, 1,25(OH) 2 D 3 exerts its effects via two independent signal transduction pathways: the classical genomic and the non-genomic pathway. While non-genomic effects of 1,25(OH) 2 D 3 are in part exerted via effects on intracellular calcium, genomic effects are mediated by the vitamin D receptor (VDR). Recent findings convincingly support the concept of a new function of the VDR as a tumor suppressor in skin, with key components of the vitamin D endocrine system, including VDR, CYP24A1, CYP27A1, and CYP27B1 being strongly expressed in non-melanoma skin cancer (NMSC). It has now been shown that anti-tumor effects of VDR, that include some of its ligand-induced growth-regulatory effects, are at least in part mediated by interacting in a highly coordinated manner with the p53 family (p53/p63/p73) in response to a large number of alterations in cell homeostasis, including UV-induced DNA damage, a hallmark for skin photocarcinogenesis. Considering the relevance of the vitamin D endocrine system for carcinogenesis of skin cancer, it is not surprising that low 25(OH)D serum concentrations and genetic variants (SNPs) of the vitamin D endocrine system have been identified as potential risk factors for occurrence and prognosis of skin malignancies. In conclusion, an increasing body of evidence now convincingly supports the concept that the vitamin D endocrine system is of relevance for photocarcinogenesis and progression of NMSC and that its pharmacologic modulation by vitamin D, 1,25(OH) 2 D 3, and analogs represents a promising new strategy for prevention and/or treatment of these malignancies. Copyright © 2017 Elsevier B.V. All rights reserved.

Training our future endocrine surgeons: a look at the endocrine surgery operative experience of U.S. surgical residents.

PubMed

Zarebczan, Barbara; McDonald, Robert; Rajamanickam, Victoria; Leverson, Glen; Chen, Herbert; Sippel, Rebecca S

2010-12-01

During the last 10 years, the number of endocrine procedures performed in the United States has increased significantly. We sought to determine whether this has translated into an increase in operative volume for general surgery and otolaryngology residents. We evaluated records from the Resident Statistic Summaries of the Residency Review Committee (RRC) for U.S. general surgery and otolaryngology residents for the years 2004-2008, specifically examining data on thyroidectomies and parathyroidectomies. Between 2004 and 2008, the average endocrine case volume of U.S. general surgery and otolaryngology residents increased by approximately 15%, but otolaryngology residents performed more than twice as many operations as U.S. general surgery residents. The growth in case volume was mostly from increases in the number of thyroidectomies performed by U.S. general surgery and otolaryngology residents (17.9 to 21.8, P = .007 and 46.5 to 54.4, P = .04). Overall, otolaryngology residents also performed more parathyroidectomies than their general surgery counterparts (11.6 vs 8.8, P = .007). Although there has been an increase in the number of endocrine cases performed by graduating U.S. general surgery residents, this is significantly smaller than that of otolaryngology residents. To remain competitive, general surgery residents wishing to practice endocrine surgery may need to pursue additional fellowship training. Copyright © 2010 Mosby, Inc. All rights reserved.

QSAR PRIORITIZATION OF CHEMICAL INVENTORIES FOR ENDOCRINE DISRUPTOR TESTING

EPA Science Inventory

Binding affinity between chemicals and the estrogen receptor (ER) serves as an indicator of the potential to cause endocrine disruption through this receptor-mediated endocrine pathway. Estimating ER binding affinity is, therefore, one strategic approach to reducing the costs of ...

Tumour suppressor menin is essential for development of the pancreatic endocrine cells.

PubMed

Fontanière, Sandra; Duvillié, Bertrand; Scharfmann, Raphaël; Carreira, Christine; Wang, Zhao-Qi; Zhang, Chang-Xian

2008-11-01

Mutations of the multiple endocrine neoplasia type 1 (MEN1) gene predispose patients to MEN1 that affects mainly endocrine tissues, suggesting important physiological functions of the gene in adult endocrine cells. Homozygous disruption of Men1 in mice causes embryonic lethality, whereas the eventual involvement of the gene in embryonic development of the endocrine cells remains unknown. Here, we show that homozygous Men1 knockout mice demonstrate a reduced number of glucagon-positive cells in the E12.5 pancreatic bud associated with apoptosis, whereas the exocrine pancreas development in these mice is not affected. Our data suggest that menin is involved in the survival of the early pancreatic endocrine cells during the first developmental transition. Furthermore, chimerism assay revealed that menin has an autonomous and specific effect on the development of islet cells. In addition, using pancreatic bud culture mimicking the differentiation of alpha- and beta-cells during the second transition, we show that loss of menin leads to the failure of endocrine cell development, altered pancreatic structure and a markedly decreased number of cells expressing neurogenin 3, indicating that menin is also required at this stage of the endocrine pancreas development. Taken together, our results suggest that menin plays an indispensable role in the development of the pancreatic endocrine cells.

Circadian Clock Control of Endocrine Factors

PubMed Central

Gamble, Karen L.; Berry, Ryan; Frank, Stuart J.; Young, Martin E.

2015-01-01

Organisms experience dramatic fluctuations in demands/stresses over the course of the day. In order to maintain biological processes within physiologic boundaries, it is imperative that mechanisms have evolved for anticipation of, and adaptation to, these daily fluctuations. Endocrine factors undoubtedly play an integral role in homeostasis. Not only do circulating levels of various endocrine factors oscillate over the 24 period, but so too does responsiveness of target tissues to these signals/stimuli. Emerging evidence suggests that these daily oscillations do not occur solely in response to behavioral fluctuations associated with sleep/wake and feeding/fasting cycles, but are orchestrated in part by an intrinsic timekeeping mechanism known as the circadian clock. Disruption of circadian clocks, through genetic and/or environmental means, appears to precipitate numerous common disorders, including cardiometabolic diseases and cancer. Collectively, these observations, which are reviewed within the current article, have led to suggestion that strategies designed to realign normal circadian rhythmicities hold a therapeutic potential for the treatment of various endocrine-related disorders. PMID:24863387

Endocrine disorders which manifest in the lower extremity.

PubMed

Rubenstein, S A; Boxer, M C

1985-10-01

This article has attempted to alert the podiatric medical practitioner to those endocrine disorders which have pedal manifestations. With the clinical information presented here, the podiatrist is in a unique position to identify early signs of endocrine disease. By doing so, the podiatric practitioner may play a vital role as a member of the primary care team.

Fish and wildlife species as sentinels of environmental endocrine disruption

USGS Publications Warehouse

Sheffield, S.R.; Matter, J.M.; Rattner, B.A.; Guiney, P.D.; Kendall, Ronald J.; Dickerson, Richard L.; Giesy, John P.; Suk, William P.

1998-01-01

This chapter provides an overview of the history and criteria for use of captive and free-ranging fish and wildlife (amphibians, reptiles, birds, and mammals) species as sentinels of potential environmental endocrine disruption. Biochemical, behavioral, physiological, immunological, genetic, reproductive, developmental, and ecological correlates of endocrine disruption in these sentinels are presented and reviewed. In addition, data needs to promote better use of sentinel species in the assessment of endocrine disruption are discussed.

Next-generation sequencing for endocrine cancers: Recent advances and challenges.

PubMed

Suresh, Padmanaban S; Venkatesh, Thejaswini; Tsutsumi, Rie; Shetty, Abhishek

2017-05-01

Contemporary molecular biology research tools have enriched numerous areas of biomedical research that address challenging diseases, including endocrine cancers (pituitary, thyroid, parathyroid, adrenal, testicular, ovarian, and neuroendocrine cancers). These tools have placed several intriguing clues before the scientific community. Endocrine cancers pose a major challenge in health care and research despite considerable attempts by researchers to understand their etiology. Microarray analyses have provided gene signatures from many cells, tissues, and organs that can differentiate healthy states from diseased ones, and even show patterns that correlate with stages of a disease. Microarray data can also elucidate the responses of endocrine tumors to therapeutic treatments. The rapid progress in next-generation sequencing methods has overcome many of the initial challenges of these technologies, and their advantages over microarray techniques have enabled them to emerge as valuable aids for clinical research applications (prognosis, identification of drug targets, etc.). A comprehensive review describing the recent advances in next-generation sequencing methods and their application in the evaluation of endocrine and endocrine-related cancers is lacking. The main purpose of this review is to illustrate the concepts that collectively constitute our current view of the possibilities offered by next-generation sequencing technological platforms, challenges to relevant applications, and perspectives on the future of clinical genetic testing of patients with endocrine tumors. We focus on recent discoveries in the use of next-generation sequencing methods for clinical diagnosis of endocrine tumors in patients and conclude with a discussion on persisting challenges and future objectives.

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...

Multiple endocrine diseases in cats: 15 cases (1997-2008).

PubMed

Blois, Shauna L; Dickie, Erica L; Kruth, Stephen A; Allen, Dana G

2010-08-01

The objective of this retrospective study was to characterize a population of cats from a tertiary care center diagnosed with multiple endocrine disorders, including the specific disorders and time intervals between diagnosis of each disorder. Medical records of 15 cats diagnosed with more than one endocrine disorder were reviewed. The majority of cats were domestic shorthairs, and the mean age at the time of diagnosis of the first disorder was 10.3 years. The most common combination of disorders was diabetes mellitus and hyperthyroidism. Two cats had concurrent diabetes mellitus and hyperadrenocorticism, one cat had concurrent central diabetes insipidus and diabetes mellitus. A mean of 25.7 months elapsed between diagnoses of the first and second endocrine disorder, but this was variable. This study suggests the occurrence of multiple endocrine disorders is uncommon in cats. Copyright 2010 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.

Affective disorders and endocrine disease. New insights from psychosomatic studies.

PubMed

Fava, G A

1994-01-01

This is a review of psychosomatic interactions between affective disorders (depressive and anxiety disturbances, irritable mood) and endocrine disease. Particular reference is made to stressful life events in the pathogenesis of endocrine disease, psychopathology of hormonal disturbances, and pathophysiology of hypothalamic-pituitary-adrenal axis function in depression and Cushing's disease. These psychosomatic interactions may lead to appraisal of common etiological mechanisms in endocrine and psychiatric disorders, of the value of retaining the category of organic affective syndromes in psychiatric classification, and of the need for research on quality-of-life measures in endocrine disease. The establishment of "psychoendocrine units," where both endocrinologists and psychiatrists should work, is advocated. Such psychoendocrine units may serve and benefit clinical populations who currently defy traditional medical subdivisions.

Designing Endocrine Disruption Out of the Next Generation of Chemicals.

PubMed

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 via

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

[Novel concepts in biology of diffuse endocrine system: results and future investigations].

PubMed

Iaglov, V V; Iaglova, N V

2012-01-01

Diffuse endocrine system is a largest part of endocrine system of vertebrates. Recend findings showed that DES-cells are not neuroectodermal but have ectodermal, mesodermal, and entodermal ontogeny. The article reviews novel concept of diffuse endocrine system anatomy and physiology, functional role of DES hormones and poorly investigated aspects like DES-cell morphology, hormones secretion in normal and pathologic conditions. Further research of diffuse endocrine system has a great significance for biochemistry, morphology, and clinical medicine.

Exposures to Endocrine Disrupting Chemicals in Consumer Products-A Guide for Pediatricians.

PubMed

Wong, Katelyn H; Durrani, Timur S

2017-05-01

Endocrine disrupting chemicals, a group of exogenous chemicals that can interfere with hormone action in the body, have been implicated in disrupting endocrine function, which negatively affects human health and development. Endocrine disrupting chemicals are ubiquitously detected in consumer products, foods, beverages, personal care products, and household cleaning products. Due to concerns about their negative effects on human health, several professional health provider societies have recommended the reduction of common endocrine disrupting chemical exposures. The purpose of this review is to provide a brief overview of common endocrine disrupting chemicals (bisphenol A, phthalates, triclosan, polybrominated ethers, and parabens) and potential effects on child development and health. In addition, we aim to provide guidance and resources for pediatricians and other health care providers with counseling strategies to help patients to minimize exposures to common endocrine disrupting chemicals. Copyright © 2017 Mosby, Inc. All rights reserved.

International network on endocrine complications in thalassaemia (I-CET): an opportunity to grow.

PubMed

De Sanctis, V; Soliman, A T; Angastiniotis, M; Eleftheriou, A; Kattamis, Ch; Karimi, M; El Kholy, M; Elsedfy, H; Yassin, Mohd Abdel Daem Mohd; El Awwa, A; Stoeva, I; Skordis, N; Raiola, G; Fiscina, B

2012-04-01

Most of the endocrine complications in thalassaemia are attributable to iron overload which may be the result of economic circumstances (expense of the chelation therapy), late onset of chelation therapy or poor compliance with the iron chelation therapy. The major difficulties reported by hematologists or pediatric endocrinologists experienced in thalassaemias or thalassaemia syndromes in following growth disorders and endocrine complications were: lack of familiarity with medical treatment of endocrine complications (40%), interpretation of endocrine tests (30%), costs (65%), absence of paediatric endocrinologist for consultation on growth disorders and endocrine complications (27%), facilities (27%), other (e.g. lack of collaboration and on-time consultation between thalassaemic Centers supervised by hematologists and endocrinologists) (17%). Because any progress we make in research into growth disorders and endocrine complications in thalassaemia should be passed on to all those suffering from it, guaranteeing them the same therapeutic benefits and the same quality of life, on the 8th of May, 2009 in Ferrara (Italy), the International Network on Endocrine Complications in Thalassemia (I-CET) was founded. The I-CET group is planning to conduct, in Ferrara in May 2012, a workshop, "MRI and Endocrine Complications in Thalassaemia", and in Doha (Qatar) in September 2012, a 3-day intensive course entitled, "Growth disorders and Endocrine Complications in Thalassaemia", to provide interested pediatricians, physicians and hematologists from all over the world with an in-depth approach to the diagnosis and management of growth and endocrine disorders in thalassaemic patients.

[Calciotropic actions of parathyroid hormone and vitamin D-endocrine system].

PubMed

Avila, Euclides; Barrera, David; Díaz, Lorenza

2007-01-01

Parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D [1,25-(OH)zD] participate in systemic regulation of calcium homeostasis through endocrine effects mediated via the specific receptors PTHR1 and VDR, expressed in bone, kidney, intestine and parathyroid glands. In bone, both hormones PTH and 1,25-(OH)2D promote calcium release into the circulation; however, they also have anabolic effects in this tissue. In kidney, PTH controls 1,25-(OH)2D synthesis, and together both hormones stimulate calcium reabsorption. The most important calciotropic action of 1,25-(OH)2D is stimulation of intestinal calcium absorption. In the parathyroid glands, 1,25-(OH)2D regulates PTH synthesis through a negative feedback mechanism, while modulating the gland growth. Finally, a general overview of the maternal adaptations regarding calcium homeostasis during pregnancy and lactation is presented.

Functional Hypothalamic Amenorrhea: An Endocrine Society Clinical Practice Guideline.

PubMed

Gordon, Catherine M; Ackerman, Kathryn E; Berga, Sarah L; Kaplan, Jay R; Mastorakos, George; Misra, Madhusmita; Murad, M Hassan; Santoro, Nanette F; Warren, Michelle P

2017-05-01

The American Society for Reproductive Medicine, the European Society of Endocrinology, and the Pediatric Endocrine Society. This guideline was funded by the Endocrine Society. To formulate clinical practice guidelines for the diagnosis and treatment of functional hypothalamic amenorrhea (FHA). The participants include an Endocrine Society-appointed task force of eight experts, a methodologist, and a medical writer. This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation approach to describe the strength of recommendations and the quality of evidence. The task force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies. One group meeting, several conference calls, and e-mail communications enabled consensus. Endocrine Society committees and members and cosponsoring organizations reviewed and commented on preliminary drafts of this guideline. FHA is a form of chronic anovulation, not due to identifiable organic causes, but often associated with stress, weight loss, excessive exercise, or a combination thereof. Investigations should include assessment of systemic and endocrinologic etiologies, as FHA is a diagnosis of exclusion. A multidisciplinary treatment approach is necessary, including medical, dietary, and mental health support. Medical complications include, among others, bone loss and infertility, and appropriate therapies are under debate and investigation. Copyright © 2017 Endocrine Society

Specifying pancreatic endocrine cell fates.

PubMed

Collombat, Patrick; Hecksher-Sørensen, Jacob; Serup, Palle; Mansouri, Ahmed

2006-07-01

Cell replacement therapy could represent an attractive alternative to insulin injections for the treatment of diabetes. However, this approach requires a thorough understanding of the molecular switches controlling the specification of the different pancreatic cell-types in vivo. These are derived from an apparently identical pool of cells originating from the early gut endoderm, which are successively specified towards the pancreatic, endocrine, and hormone-expressing cell lineages. Numerous studies have outlined the crucial roles exerted by transcription factors in promoting the cell destiny, defining the cell identity and maintaining a particular cell fate. This review focuses on the mechanisms regulating the morphogenesis of the pancreas with particular emphasis on recent findings concerning the transcription factor hierarchy orchestrating endocrine cell fate allocation.

Endocrine Disruptors: Adverse Health Effects Mediated by EGFR?

PubMed

Stolz, Ailine; Schönfelder, Gilbert; Schneider, Marlon R

2018-02-01

Although endocrine disruptors represent a serious concern to human health, the underlying molecular mechanisms leading to diseases such as cancer remain poorly understood. Recent work has uncovered the epidermal growth factor receptor (EGFR) as a possible mediator of these adverse health effects, with important implications for the role of endocrine disruptors in human diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Histological effects of short term endocrine therapy on prostatic cancer].

PubMed

Irisawa, C; Yoshimura, Y; Yokota, T; Yamaguchi, O; Kondou, Y; Hamasaki, T; Yamad, Y; Kurosu, S; Chiba, R

1996-07-01

The objective of this study is to investigate the pathological changes which occurred in prostatic cancer shortly after the commencement of endocrine therapy. Fourty-three patients underwent radical prostatectomy immediately after the short term endocrine therapy (treatment period was within one month) and the histological pictures of operative specimens were compared to those obtained from the pretreatment biopsy specimens. Degenerative changes of cancer cells, such as nuclear and cytoplasmic vacuole, collapse of the cytoplasm and the appearance of naked hyperchromatic nucleus were noticed after the short term endocrine therapy. Especially in the cases which were histologically evaluated to be poorly differentiated in the biopsy specimens, not only degenerative changes but also destruction of cancer nests caused by cell death were observed. The histological effects affected by short term endocrine treatment had no relation to the prognosis, but in the cases of stage D2, the pathological grade judged by post-therapeutic specimens were found to be useful for the prediction of prognosis. Endocrine therapy induces remarkable pathological changes in prostatic cancer within a very short time after beginning treatment.

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

To Modulate and Be Modulated: Estrogenic Influences on Auditory Processing of Communication Signals within a Socio-Neuro-Endocrine Framework

PubMed Central

Yoder, Kathleen M.; Vicario, David S.

2012-01-01

Gonadal hormones modulate behavioral responses to sexual stimuli, and communication signals can also modulate circulating hormone levels. In several species, these combined effects appear to underlie a two-way interaction between circulating gonadal hormones and behavioral responses to socially salient stimuli. Recent work in songbirds has shown that manipulating local estradiol levels in the auditory forebrain produces physiological changes that affect discrimination of conspecific vocalizations and can affect behavior. These studies provide new evidence that estrogens can directly alter auditory processing and indirectly alter the behavioral response to a stimulus. These studies show that: 1. Local estradiol action within an auditory area is necessary for socially-relevant sounds to induce normal physiological responses in the brains of both sexes; 2. These physiological effects occur much more quickly than predicted by the classical time-frame for genomic effects; 3. Estradiol action within the auditory forebrain enables behavioral discrimination among socially-relevant sounds in males; and 4. Estradiol is produced locally in the male brain during exposure to particular social interactions. The accumulating evidence suggests a socio-neuro-endocrinology framework in which estradiol is essential to auditory processing, is increased by a socially relevant stimulus, acts rapidly to shape perception of subsequent stimuli experienced during social interactions, and modulates behavioral responses to these stimuli. Brain estrogens are likely to function similarly in both songbird sexes because aromatase and estrogen receptors are present in both male and female forebrain. Estrogenic modulation of perception in songbirds and perhaps other animals could fine-tune male advertising signals and female ability to discriminate them, facilitating mate selection by modulating behaviors. Keywords: Estrogens, Songbird, Social Context, Auditory Perception PMID:22201281

Epithelial to mesenchymal transition in human endocrine islet cells

PubMed Central

Moreno-Amador, José Luis; Téllez, Noèlia; Marin, Sandra; Aloy-Reverté, Caterina; Semino, Carlos; Nacher, Montserrat

2018-01-01

Background β-cells undergo an epithelial to mesenchymal transition (EMT) when expanded in monolayer culture and give rise to highly proliferative mesenchymal cells that retain the potential to re-differentiate into insulin-producing cells. Objective To investigate whether EMT takes place in the endocrine non-β cells of human islets. Methodology Human islets isolated from 12 multiorgan donors were dissociated into single cells, purified by magnetic cell sorting, and cultured in monolayer. Results Co-expression of insulin and the mesenchymal marker vimentin was identified within the first passage (p1) and increased subsequently (insulin+vimentin+ 7.2±6% at p1; 43±15% at p4). The endocrine non-β-cells did also co-express vimentin (glucagon+vimentin+ 59±1.5% and 93±6%, somatostatin+vimentin+ 16±9.4% and 90±10% at p1 and p4 respectively; PP+vimentin+ 74±14% at p1; 88±12% at p2). The percentage of cells expressing only endocrine markers was progressively reduced (0.6±0.2% insulin+, 0.2±0.1% glucagon+, and 0.3±0.2% somatostatin+ cells at p4, and 0.7±0.3% PP+ cells at p2. Changes in gene expression were also indicated of EMT, with reduced expression of endocrine markers and the epithelial marker CDH-1 (p<0.01), and increased expression of mesenchymal markers (CDH-2, SNAI2, ZEB1, ZEB2, VIM, NT5E and ACTA2; p<0.05). Treatment with the EMT inhibitor A83-01 significantly reduced the percentage of co-expressing cells and preserved the expression of endocrine markers. Conclusions In adult human islets, all four endocrine islet cell types undergo EMT when islet cells are expanded in monolayer conditions. The presence of EMT in all islet endocrine cells could be relevant to design of strategies aiming to re-differentiate the expanded islet cells towards a β-cell phenotype. PMID:29360826

Endocrine control of epigenetic mechanisms in male reproduction.

PubMed

Ankolkar, Mandar; Balasinor, N H

2016-01-01

Endocrine control of reproduction is very well known and has been echoed by many research groups. However, recent developments point to the ability of toxic endocrine disrupting chemicals (EDC) to alter epigenetic information of the gametes which gets transferred to the developing embryo and affects the immediate reproductive outcome or even persists transgenerationally. These epigenetic aberrations contribute to the ensuing pathophysiology of reproductive disorders. Investigations of the female in cases of poor reproductive outcome have been the main strategy towards diagnosis. However, despite the male partner contributing half of his genome to the progeny, thorough investigations in the male have been ignored. Environmental pollutants are all pervading and are encountered in our day-to-day life. Many of these pollutants have potential to disrupt the endocrine system. Here, we discuss how the male gametes (spermatozoa) are susceptible to a myriad of epigenetic insults inflicted by exposure to endocrine disruptors and how important is the contribution of the epigenetic marks of the spermatozoa in healthy reproduction. We advocate that sperm epigenetics should be considered as a significant contributor to reproductive health and should be researched further and be subsequently included in routine diagnostic workup in cases of poor reproductive outcome.

Endocrine cells in human Bartholin's glands. An immunohistochemical and ultrastructural analysis.

PubMed

Fetissof, F; Arbeille, B; Bellet, D; Barre, I; Lansac, J

1989-01-01

Endocrine cells were investigated in human Bartholin's glands by use of histochemical, immunohistochemical and ultrastructural methods. Endocrine cells represent normal constituents of these glands, being mainly distributed throughout the transitional epithelium of the major excretory duct; however, single elements are dispersed among the acinar lobules. Serotonin-, calcitonin-, katacalcin-, bombesin- and alpha-hCG-immunoreactive cells were recognized, with serotonin-immunoreactive cells predominating. Co-expression of calcitonin, katacalcin or alpha-hCG with serotonin was observed in single endocrine cells. At the ultrastructural level, these cells are richly granulated and show typical neuroendocrine features. Bartholin's glands display an endocrine profile quite similar to that of other cloacal-derived tissues.

Endocrine disruption, parasites and pollutants in wild freshwater fish.

PubMed

Jobling, S; Tyler, C R

2003-01-01

Disruption of the endocrine system has been shown to occur in wild freshwater fish populations across the globe. Effects range from subtle changes in the physiology and sexual behaviour of fish to permanently altered sexual differentiation, impairment of gonad development and/or altered fertility. A wide variety of adverse environmental conditions may induce endocrine disruption, including sub-optimal temperatures, restricted food supply, low pH, environmental pollutants, and/or parasites. Furthermore, it is conceivable that any/all of these factors could act simultaneously to cause a range of disparate or inter-related effects. Some of the strongest evidence for a link between an adverse health effect, as a consequence of endocrine disruption, and a causative agent(s) is between the condition of intersex in wild roach (Rutlius rutilus) in UK rivers and exposure to effluents from sewage treatment works. The evidence to indicate that intersex in roach (and other cyprinid fish living in these rivers) is caused by chemicals that mimic and/or disrupt hormone function/balance in treated sewage effluent is substantial. There are a few parasites that affect the endocrine system directly in fish, including the tape worm Ligula intestinalis and a few parasites from the micropsora phylum. L. intestinalis acts at the level of the hypothalamus restricting GnRH secretion (resulting in poorly developed gonads) and is one of the very few examples where an endocrine disrupting event has been shown to result in a population-level effect (reducing it). It is well established that many parasites affect the immune system and thus the most common effect of parasites on the endocrine system in fish is likely to be an indirect one.

Diagnosis and Treatment of Endocrine Co-Morbidities in Patients with Cystic Fibrosis

PubMed Central

Siwamogsatham, Oranan; Alvarez, Jessica

2015-01-01

Purpose of review The aim of this review is to provide an update on various relevant endocrine aspects of care in adolescents and adults with cystic fibrosis (CF). Recent findings As life expectancy in CF has continuously improved, endocrine complications have become more apparent. The common endocrine complications include cystic fibrosis related diabetes (CFRD), cystic fibrosis related bone disease, vitamin D deficiency and poor growth and pubertal development. Thyroid and adrenal disorders have also been reported, although the prevalence appears to be less common. Summary Endocrine diseases are an increasingly recognized complication that has a significant impact on the overall health of individuals with CF. This review summarizes the updated screening and management of endocrine diseases in the CF population. PMID:25105995

Role of ERβ and GPR30 in the endocrine pancreas: A matter of estrogen dose.

PubMed

Ropero, Ana B; Pang, Yefei; Alonso-Magdalena, Paloma; Thomas, Peter; Nadal, Angel

2012-08-01

The endocrine pancreas has emerged as a target for estrogens. The functions of pancreatic α-, β- and δ-cells are modulated by the endogenous hormone, 17β-estradiol (E2). Low physiological concentrations (100pM-1nM) of E2 rapidly decrease the activity of the ATP-sensitive potassium channel (K(ATP)) and enhance glucose-induced insulin release in β-cells in an estrogen receptor β (ERβ)-dependent manner. In addition to the insulinotropic action of ERβ, the newly described estrogen receptor, GPR30, is involved in the insulinotropic effects of high doses of E2 (100nM-5μM). The specific GPR30 agonist G1 also increases insulin secretion in β-cells. Low glucose-induced calcium oscillations and glucagon secretion are suppressed by E2. The effects on glucagon secretion may be mediated by GPR30. Somatostatin release is also decreased by E2 and G1. In this review we summarize all the data published up to date on the rapid insulinotropic effects of estrogens in the endocrine pancreas and propose a model to integrate the estrogen actions mediated through both receptors. Copyright © 2012 Elsevier Inc. All rights reserved.

Endocrine disrupters--testing strategies to assess human hazard.

PubMed

Baker, V A

2001-01-01

During the last decade an hypothesis has been developed linking certain chemicals (natural and synthetic) to observed and suspected adverse effects on reproduction in both wildlife and humans. The issue of 'endocrine disruption' originally focused on chemicals that mimic the action of the natural hormone oestrogen. However, the concern is now encompassing effects on the whole endocrine system. In response to public awareness, regulatory agencies (including the US EPA) and the OECD are formulating potential testing strategies and have begun the process of validating defined tests to systematically assess chemicals for their endocrine-disrupting activities. In order to investigate chemicals that have the potential to cause endocrine disruption, a large number of in vitro and in vivo assays have been identified. In vitro test systems (particularly when used in combination) offer the possibility of providing an early screen for large numbers of chemicals and can be useful in characterising the mechanism of action and potency. In vitro assays in widespread use for the screening/characterisation of endocrine disrupting potential include hormone receptor ligand binding assays (determination of the ability of a chemical to bind to the hormone receptor), cell proliferation assays (analysis of the ability of a chemical to stimulate growth of oestrogen sensitive cells), reporter gene assays in yeast or mammalian cells (analysis of the ability of a chemical to stimulate the transcription of a reporter gene construct in cell culture), and the analysis of the regulation of endogenous oestrogen sensitive genes in cell lines. However, in vitro assays do not always reliably predict the outcome in vivo due to differences in metabolic capabilities of the test systems used and the diverse range of mechanisms by which endocrine disrupting chemicals may act. Therefore a complementary battery of short- and long-term in vitro and in vivo assays (that assess both receptor and non

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. Copyright © 2014 Elsevier Inc. All rights reserved.

Polish Society of Endocrinology Position statement on endocrine disrupting chemicals (EDCs).

PubMed

Rutkowska, Aleksandra; Rachoń, Dominik; Milewicz, Andrzej; Ruchała, Marek; Bolanowski, Marek; Jędrzejuk, Diana; Bednarczuk, Tomasz; Górska, Maria; Hubalewska-Dydejczyk, Alicja; Kos-Kudła, Beata; Lewiński, Andrzej; Zgliczyński, Wojciech

2015-01-01

With the reference to the position statements of the Endocrine Society, the Paediatric Endocrine Society, and the European Society of Paediatric Endocrinology, the Polish Society of Endocrinology points out the adverse health effects caused by endocrine disrupting chemicals (EDCs) commonly used in daily life as components of plastics, food containers, pharmaceuticals, and cosmetics. The statement is based on the alarming data about the increase of the prevalence of many endocrine disorders such as: cryptorchidism, precocious puberty in girls and boys, and hormone-dependent cancers (endometrium, breast, prostate). In our opinion, it is of human benefit to conduct epidemiological studies that will enable the estimation of the risk factors of exposure to EDCs and the probability of endocrine disorders. Increasing consumerism and the industrial boom has led to severe pollution of the environment with a corresponding negative impact on human health; thus, there is great necessity for the biomonitoring of EDCs in Poland.

Endocrine changes in male stumptailed macaques (Macaca arctoides) as a response to odor stimulation with vaginal secretions.

PubMed

Cerda-Molina, Ana Lilia; Hernández-López, Leonor; Chavira, Roberto; Cárdenas, Mario; Paez-Ponce, Denisse; Cervantes-De la Luz, Harry; Mondragón-Ceballos, Ricardo

2006-01-01

In mammalian species, social chemosignals are important in modulating endocrine reproductive functions. In nonhuman primates, previous studies have described a high frequency of mounting behavior by females in the follicular and periovulatory phases of the menstrual cycle. Stumptailed macaque females do not signal receptivity by means of sexual swellings, as do others macaques, therefore providing a good model in which to study chemical signaling of reproductive status. We exposed anesthetized stumptailed males to vaginal secretions of either late follicular or menses phase or to saline solution to determine the endocrine changes promoting male sexual behavior. In males exposed to follicular secretions, plasma testosterone concentrations were sustained up to 120 min after exposure. Such an effect was not observed in animals exposed to menses or saline odor sources. A luteinizing hormone surge, occurring 30 minutes after exposure to late follicular phase secretion swabs, preceded this sustained testosterone effect. The fact that late follicular scents induce sustained testosterone concentrations provides support to the idea that stumptailed males draw information concerning female reproductive status from the female's vaginal odor.

Development of a Multidisciplinary, Multicampus Subspecialty Practice in Endocrine Cancers

PubMed Central

Bible, Keith C.; Smallridge, Robert C.; Morris, John C.; Molina, Julian R.; Suman, Vera J.; Copland, John A.; Rubin, Joseph; Menefee, Michael E.; Sideras, Kostandinos; Maples, William J.; McIver, Bryan; Fatourechi, Vahab; Hay, Ian; Foote, Robert L.; Garces, Yolanda I.; Kasperbauer, Jan L.; Thompson, Geoffrey B.; Grant, Clive S.; Richards, Melanie L.; Sebo, Thomas; Lloyd, Ricardo; Eberhardt, Norman L.; Reddi, Honey V.; Casler, John D.; Karlin, Nina J.; Westphal, Sydney A.; Richardson, Ronald L.; Buckner, Jan C.; Erlichman, Charles

2012-01-01

Purpose: Relative to more abundant neoplasms, endocrine cancers have been historically neglected, yet their incidence is increasing. We therefore sought to build interest in endocrine cancers, improve physician experience, and develop innovative approaches to treating patients with these neoplasms. Methods: Between 2005 and 2010, we developed a multidisciplinary Endocrine Malignancies Disease Oriented Group involving all three Mayo Clinic campuses (Rochester, MN; Jacksonville, FL; and Scottsdale, AZ). In response to higher demand at the Rochester campus, we sought to develop a Subspecialty Tumor Group and an Endocrine Malignancies Tumor Clinic within the Division of Medical Oncology. Results: The intended groups were successfully formed. We experienced difficulty in integration of the Mayo Scottsdale campus resulting from local uncertainty as to whether patient volumes would be sufficient to sustain the effort at that campus and difficulty in developing enthusiasm among clinicians otherwise engaged in a busy clinical practice. But these obstacles were ultimately overcome. In addition, with respect to the newly formed medical oncology subspecialty endocrine malignancies group, appointment volumes quadrupled within the first year and increased seven times within two years. The number of active therapeutic endocrine malignancies clinical trials also increased from one in 2005 to five in 2009, with all three Mayo campuses participating. Conclusion: The development of subspecialty tumor groups for uncommon malignancies represents an effective approach to building experience, increasing patient volumes and referrals, and fostering development of increased therapeutic options and clinical trials for patients afflicted with otherwise historically neglected cancers. PMID:22942830

Practice patterns and job satisfaction in fellowship-trained endocrine surgeons.

PubMed

Tsinberg, Michael; Duh, Quan-Yang; Cisco, Robin M; Gosnell, Jessica E; Scholten, Anouk; Clark, Orlo H; Shen, Wen T

2012-12-01

Debates about the difficult job market for young endocrine surgeons are ongoing. This study aimed to analyze the practice patterns and work-related satisfaction levels of recently trained endocrine surgeons. An anonymous survey was utilized. Participants were divided into 3 groups: "Young" (<3 years in practice), "middle" (3-5 years), and "older" (>5 years). Fifty-six of 78 surgeons (72%) responded to the survey. Time in practice ranged from 1 to 9 years (mean, 3.9 ± 0.28). Forty-five (80%) described their practice as academic. Participants performed 244.1 ± 17.8 operations within the last year; 75.4 ± 3.3% were endocrine cases. More surgeons in the "young" group have academic practices (92%) and joined established endocrine surgery groups (54%) versus older surgeons (67% and 42%; P = .05). Of surgeons in the "young" group, 4% started their own practice versus 33% in the "older" group (P = .04). Level of satisfaction with financial compensation (3.2 on a 4-point scale versus 2.9) and lifestyle (3.6 vs 3.1) was also higher in the younger group (P = .009). Despite widespread speculation about scarcity of academic jobs after fellowship, recently trained endocrine surgeons are more likely to practice in academic settings and join established endocrine surgery practices when compared with older surgeons. Overall satisfaction level is higher among recently trained surgeons. Copyright © 2012 Mosby, Inc. All rights reserved.

Morphological and transcriptomic effects of endocrine modulators on the gonadal differentiation of chicken embryos: The case of tributyltin (TBT).

PubMed

Scheider, Jessica; Afonso-Grunz, Fabian; Jessl, Luzie; Hoffmeier, Klaus; Winter, Peter; Oehlmann, Jörg

2018-03-01

Morphological malformations induced by tributyltin (TBT) exposure during embryonic development have already been characterized in various taxonomic groups, but, nonetheless, the molecular processes underlying these changes remain obscure. The present study provides the first genome-wide screening for differentially expressed genes that are linked to morphological alterations of gonadal tissue from chicken embryos after exposure to TBT. We applied a single injection of TBT (between 0.5 and 30 pg as Sn/g egg) into incubated fertile eggs to simulate maternal transfer of the endocrine disruptive compound. Methyltestosterone (MT) served as a positive control (30 pg/g egg). After 19 days of incubation, structural features of the gonads as well as genome-wide gene expression profiles were assessed simultaneously. TBT induced significant morphological and histological malformations of gonadal tissue from female embryos that show a virilization of the ovaries. This phenotypical virilization was mirrored by altered expression profiles of sex-dependent genes. Among these are several transcription and growth factors (e.g. FGF12, CTCF, NFIB), whose altered expression might serve as a set of markers for early identification of endocrine active chemicals that affect embryonic development by transcriptome profiling without the need of elaborate histological analyses. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

A RESEARCH AGENDA FOR RISK MANAGEMENT OF ENDOCRINE DISRUPTING CHEMICALS

EPA Science Inventory

To date, research on suspected endocrine disrupting chemicals (EDCs) has focused on determining health effects in humans and wildlife and on occurrence of these chemicals in the environment. There is strong evidence that certain chemicals are causing endocrine-related effects in...

Rhythms in the endocrine system of fish: a review.

PubMed

Cowan, Mairi; Azpeleta, Clara; López-Olmeda, Jose Fernando

2017-12-01

The environment which living organisms inhabit is not constant and many factors, such as light, temperature, and food availability, display cyclic and predictable variations. To adapt to these cyclic changes, animals present biological rhythms in many of their physiological variables, timing their functions to occur when the possibility of success is greatest. Among these variables, many endocrine factors have been described as displaying rhythms in vertebrates. The aim of the present review is to provide a thorough review of the existing knowledge on the rhythms of the endocrine system of fish by examining the hormones that show rhythmicity, how environmental factors control these rhythms and the variation in the responses of the endocrine system depending on the time of the day. We mainly focused on the hypothalamic-pituitary axis, which can be considered as the master axis of the endocrine system of vertebrates and regulates a great variety of functions, including reproduction, growth, metabolism, energy homeostasis, stress response, and osmoregulation. In addition, the rhythms of other hormones, such as melatonin and the factors, produced in the gastrointestinal system of fish are reviewed.

Prognostic Value of p16 Status on the Development of a Complete Response in Involved Oropharynx Cancer Neck Nodes After Cisplatin-Based Chemoradiation: A Secondary Analysis of NRG Oncology RTOG 0129

DOE Office of Scientific and Technical Information (OSTI.GOV)

Galloway, Thomas J., E-mail: thomas.galloway@fccc.edu; Zhang, Qiang; Nguyen-Tan, Phuc Felix

Purpose: To determine the relationship between p16 status and the regional response of patients with node-positive oropharynx cancer treated on NRG Oncology RTOG 0129. Methods and Materials: Patients with N1-N3 oropharynx cancer and known p16 status who underwent treatment on RTOG 0129 were analyzed. Pathologic complete response (pCR) rates in patients treated with a postchemoradiation neck dissection (with p16-positive or p16-negative cancer) were compared by Fisher exact test. Patients managed expectantly were compared with those treated with a neck dissection. Results: Ninety-nine (34%) of 292 patients with node-positive oropharynx cancer and known p16 status underwent a posttreatment neck dissection (p16-positive:more » n=69; p16-negative: n=30). The remaining 193 patients with malignant lymphadenopathy at diagnosis were observed. Neck dissection was performed a median of 70 (range, 17-169) days after completion of chemoradiation. Neither the pretreatment nodal stage (P=.71) nor the postradiation, pre-neck dissection clinical/radiographic neck assessment (P=.42) differed by p16 status. A pCR was more common among p16-positive patients (78%) than p16-negative patients (53%, P=.02) and was associated with a reduced incidence of local–regional failure (hazard ratio 0.33, P=.003). On multivariate analysis of local–regional failure, a test for interaction between pCR and p16 status was not significant (P=.37). One-hundred ninety-three (66%) of 292 of initially node-positive patients were managed without a posttreatment neck dissection. Development of a clinical (cCR) was not significantly influenced by p16-status (P=.42). Observed patients with a clinical nodal CR had disease control outcomes similar to those in patients with a pCR neck dissection. Conclusions: Patients with p16-positive tumors had significantly higher pCR and locoregional control rates than those with p16-negative tumors.« less

Prognostic Value of p16 Status on the Development of a Complete Response in Involved Oropharynx Cancer Neck Nodes After Cisplatin-Based Chemoradiation: A Secondary Analysis of NRG Oncology RTOG 0129.

PubMed

Galloway, Thomas J; Zhang, Qiang Ed; Nguyen-Tan, Phuc Felix; Rosenthal, David I; Soulieres, Denis; Fortin, André; Silverman, Craig L; Daly, Megan E; Ridge, John A; Hammond, J Alexander; Le, Quynh-Thu

2016-10-01

To determine the relationship between p16 status and the regional response of patients with node-positive oropharynx cancer treated on NRG Oncology RTOG 0129. Patients with N1-N3 oropharynx cancer and known p16 status who underwent treatment on RTOG 0129 were analyzed. Pathologic complete response (pCR) rates in patients treated with a postchemoradiation neck dissection (with p16-positive or p16-negative cancer) were compared by Fisher exact test. Patients managed expectantly were compared with those treated with a neck dissection. Ninety-nine (34%) of 292 patients with node-positive oropharynx cancer and known p16 status underwent a posttreatment neck dissection (p16-positive: n=69; p16-negative: n=30). The remaining 193 patients with malignant lymphadenopathy at diagnosis were observed. Neck dissection was performed a median of 70 (range, 17-169) days after completion of chemoradiation. Neither the pretreatment nodal stage (P=.71) nor the postradiation, pre-neck dissection clinical/radiographic neck assessment (P=.42) differed by p16 status. A pCR was more common among p16-positive patients (78%) than p16-negative patients (53%, P=.02) and was associated with a reduced incidence of local-regional failure (hazard ratio 0.33, P=.003). On multivariate analysis of local-regional failure, a test for interaction between pCR and p16 status was not significant (P=.37). One-hundred ninety-three (66%) of 292 of initially node-positive patients were managed without a posttreatment neck dissection. Development of a clinical (cCR) was not significantly influenced by p16-status (P=.42). Observed patients with a clinical nodal CR had disease control outcomes similar to those in patients with a pCR neck dissection. Patients with p16-positive tumors had significantly higher pCR and locoregional control rates than those with p16-negative tumors. Copyright © 2016 Elsevier Inc. All rights reserved.

ECETOC Florence workshop on risk assessment of endocrine substances, including the potency concept.

PubMed

Fegert, Ivana

2013-12-16

The European regulation on plant protection products (1107/2009) and the Biocidal Products Regulation (EC Regulation 528/2012) only support the marketing and use of chemicals if they do not cause endocrine disruption in humans or wildlife species. Also, substances with endocrine properties are subject to authorization under the European regulation on the registration, evaluation, authorization and restriction of chemicals (REACH; 1907/2006). Therefore, the regulatory consequences of identifying a substance as an endocrine disrupting chemical are severe. In contrast to that, basic scientific criteria, necessary to define endocrine disrupting properties, are not described in any of these legislative documents. Thus, the European Center for Ecotoxicology and Toxicology of Chemicals (ECETOC) established a task force to provide scientific criteria for the identification and assessment of chemicals with endocrine disrupting properties that may be used within the context of these three legislative texts (ECETOC, 2009a). In 2009, ECETOC introduced a scientific framework as a possible concept for identifying endocrine disrupting properties within a regulatory context (ECETOC, 2009b; Bars et al., 2011a,b). The proposed scientific criteria integrated, in a weight of evidence approach, information from regulatory (eco)toxicity studies and mechanistic/screening studies by combining evidence for adverse effects detected in apical whole-organism studies with an understanding of the mode of action (MoA) of endocrine toxicity. However, since not all chemicals with endocrine disrupting properties are of equal hazard, an adequate concept should also be able to differentiate between chemicals with endocrine properties of low concern from those of higher concern (for regulatory purposes). For this purpose, the task force refined this part of their concept. Following an investigation of the key factors at a second workshop of invited regulatory, academic and industry scientists, the

Minireview: Role of Intracellular Scaffolding Proteins in the Regulation of Endocrine G Protein-Coupled Receptor Signaling

PubMed Central

Walther, Cornelia

2015-01-01

The majority of hormones stimulates and mediates their signal transduction via G protein-coupled receptors (GPCRs). The signal is transmitted into the cell due to the association of the GPCRs with heterotrimeric G proteins, which in turn activates an extensive array of signaling pathways to regulate cell physiology. However, GPCRs also function as scaffolds for the recruitment of a variety of cytoplasmic protein-interacting proteins that bind to both the intracellular face and protein interaction motifs encoded by GPCRs. The structural scaffolding of these proteins allows GPCRs to recruit large functional complexes that serve to modulate both G protein-dependent and -independent cellular signaling pathways and modulate GPCR intracellular trafficking. This review focuses on GPCR interacting PSD95-disc large-zona occludens domain containing scaffolds in the regulation of endocrine receptor signaling as well as their potential role as therapeutic targets for the treatment of endocrinopathies. PMID:25942107

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...

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 ...

Update on the Mammalian Tier 1 Endocrine Disruptor Screening Protocols

EPA Science Inventory

The endocrine system provides a number of target sites that may be susceptible to disruption by environmental agents. In response to emerging concerns that environmental chemicals may have adverse effects on human health by altering the function of the endocrine system (http://w...

How can we estimate natural selection on endocrine traits? Lessons from evolutionary biology

PubMed Central

2016-01-01

An evolutionary perspective can enrich almost any endeavour in biology, providing a deeper understanding of the variation we see in nature. To this end, evolutionary endocrinologists seek to describe the fitness consequences of variation in endocrine traits. Much of the recent work in our field, however, follows a flawed approach to the study of how selection shapes endocrine traits. Briefly, this approach relies on among-individual correlations between endocrine phenotypes (often circulating hormone levels) and fitness metrics to estimate selection on those endocrine traits. Adaptive plasticity in both endocrine and fitness-related traits can drive these correlations, generating patterns that do not accurately reflect natural selection. We illustrate why this approach to studying selection on endocrine traits is problematic, referring to work from evolutionary biologists who, decades ago, described this problem as it relates to a variety of other plastic traits. We extend these arguments to evolutionary endocrinology, where the likelihood that this flaw generates bias in estimates of selection is unusually high due to the exceptional responsiveness of hormones to environmental conditions, and their function to induce adaptive life-history responses to environmental variation. We end with a review of productive approaches for investigating the fitness consequences of variation in endocrine traits that we expect will generate exciting advances in our understanding of endocrine system evolution. PMID:27881753

Pathophysiology of the Effects of Alcohol Abuse on the Endocrine System

PubMed Central

Rachdaoui, Nadia; Sarkar, Dipak K.

2017-01-01

Alcohol can permeate virtually every organ and tissue in the body, resulting in tissue injury and organ dysfunction. Considerable evidence indicates that alcohol abuse results in clinical abnormalities of one of the body’s most important systems, the endocrine system. This system ensures proper communication between various organs, also interfacing with the immune and nervous systems, and is essential for maintaining a constant internal environment. The endocrine system includes the hypothalamic–pituitary–adrenal axis, the hypothalamic–pituitary–gonadal axis, the hypothalamic–pituitary–thyroid axis, the hypothalamic–pituitary–growth hormone/insulin-like growth factor-1 axis, and the hypothalamic–posterior pituitary axis, as well as other sources of hormones, such as the endocrine pancreas and endocrine adipose tissue. Alcohol abuse disrupts all of these systems and causes hormonal disturbances that may result in various disorders, such as stress intolerance, reproductive dysfunction, thyroid problems, immune abnormalities, and psychological and behavioral disorders. Studies in both humans and animal models have helped shed light on alcohol’s effects on various components of the endocrine system and their consequences. PMID:28988577

Pathophysiology of the Effects of Alcohol Abuse on the Endocrine System.

PubMed

Rachdaoui, Nadia; Sarkar, Dipak K

2017-01-01

Alcohol can permeate virtually every organ and tissue in the body, resulting in tissue injury and organ dysfunction. Considerable evidence indicates that alcohol abuse results in clinical abnormalities of one of the body's most important systems, the endocrine system. This system ensures proper communication between various organs, also interfacing with the immune and nervous systems, and is essential for maintaining a constant internal environment. The endocrine system includes the hypothalamic-pituitary-adrenal axis, the hypothalamic-pituitary-gonadal axis, the hypothalamic-pituitary-thyroid axis, the hypothalamic-pituitary-growth hormone/insulin-like growth factor-1 axis, and the hypothalamic-posterior pituitary axis, as well as other sources of hormones, such as the endocrine pancreas and endocrine adipose tissue. Alcohol abuse disrupts all of these systems and causes hormonal disturbances that may result in various disorders, such as stress intolerance, reproductive dysfunction, thyroid problems, immune abnormalities, and psychological and behavioral disorders. Studies in both humans and animal models have helped shed light on alcohol's effects on various components of the endocrine system and their consequences.

The Japanese Quail as an avian model for testing endocrine disrupting chemicals: endocrine and behavioral end points

USGS Publications Warehouse

Ottinger, M.A.; Abdelnabi, M.A.; Thompson, N.; Wu, J.; Henry, K.; Humphries, E.; Henry, P.F.P.

2000-01-01

Birds have extremely varied reproductive strategies. As such, the impact of endocrine disrupting chemicals (EDCs) can greatly differ across avian species. Precocial species, such as Japanese quail appear to be most sensitive to EDC effects during embryonic development, particularly sexual differentiation. A great deal is known about the ontogeny of Japanese quail (Coturnix japonica) relative to endocrine, neuro-endocrine, and behavioral components of reproduction. Therefore, this species provides an excellent model for understanding effects of EDCs on reproductive biology with exposure at specific stages of the life cycle. The purpose of these experiments was to conduct a 1- or 2- generation experiment with positive or negative control chemicals and to determine changes in selected end points. Japanese quail embryos were exposed to estradiol benzoate (EB; positive control) in a 2-generation design or to fadrozole (FAD; negative control) in a 1-generation design. Embryonic EB treatment resulted in significant reductions (p< 0.5) in hen day production (90.2 vs 54.1; control vs EB, resp.) and fertility (85.3 vs 33.4%, control vs EB, resp.). Males showed sharply reduced courtship and mating behaviors as well as increased lag time (26 vs 148 sec; control vs EB) in behavioral tests. Fadrozole exposure resulted in reduced hatchability of fertile eggs, particularly at higher doses. There were no significant effects on courtship and mating behavior of males although males showed an increased lag time in their responses, nally, a behavioral test for studying motor and fear responses in young chicks was used; chicks exposed to an estrogenic pesticide (methoxychlor) showed some deficits. In summary, the use of appropriate and reliable end points that are responsive to endocrine disruption are critical for assessment of EDCs. Supported in part by EPA grant R826134.

Early endocrine disruptors exposure acts on 3T3-L1 differentiation and endocrine activity

PubMed Central

Boudalia, Sofiane; Belloir, Christine; Miller, Marie-Louise; Canivenc-Lavier, Marie-Chantal

2017-01-01

Introduction: Data from last years suggested that early exposure to endocrine disruptors (EDs) can predispose newborns to endocrine dysfunction of adipocytes, obesity, and associated disorders. The implication of EDs at low doses on adipocyte development has been poorly investigated. For instance, vinclozolin (V) is a dicarboximide fungicide widely used in agriculture since the 90's, alone or in mixture with genistein (G), an isoflavonoid from Leguminosae. This study aims to identify the effect of vinclozolin alone or with genistein, on adipose tissue properties using cell culture. Methods: In steroid-free conditions, 3T3-L1 pre-adipocytes were induced to differentiate in the presence of EDs, singularly or in mixtures, for 2 days. DNA and triglyceride (TG) levels were measured on days 0, 2 and 8 of differentiation. Leptin secretion was measured only on the eighth day. Results: We show that low doses of G (25 µM) and V (0.1 µM) inhibit pre-adipocytes differentiation. This inhibition has been represented by a decreasing in DNA content (µg/well) and decreasing in TG accumulation (mg/mL) in 3T3-L1 cells. Nevertheless, V increased the anti-adipogenic properties of G. Conclusion: This study confirms that EDs singularly or in mixtures, introduced during early stages of life, could affect the differentiation and the endocrine activity of adipocytes, and can act as potential factors for obesity. PMID:28752072

[Perspectives on endocrine disruption].

PubMed

Olea, N; Fernández, M F; Araque, P; Olea-Serrano, F

2002-01-01

Two decades ago, reports of alterations in the reproductive function of some wild animal species and clear evidence of human and animal exposure to chemical substances with hormonal activity agonist and antagonist generated what is known now as the hypothesis of endocrine disruption. This is an emerging environmental health problem that has challenged some of the paradigms on which the control and regulation of the use of chemical compounds is based. The need to include in routine toxicology tests new research objectives that specifically refer to the development and growth of species and to the homeostasis and functionality of hormonal systems, has served to complicate both the evaluation of new compounds and the re-evaluation of existing ones. The repercussions on regulation and international trade have not taken long to be felt. On both sides of the Atlantic, screening systems for endocrine disrupters have been designed and established, and research programmes have been launched to characterise and quantify adverse effects on human and animal health and to develop preventive measures.

Thirty-day outcomes underestimate endocrine and exocrine insufficiency after pancreatic resection.

PubMed

Lim, Pei-Wen; Dinh, Kate H; Sullivan, Mary; Wassef, Wahid Y; Zivny, Jaroslav; Whalen, Giles F; LaFemina, Jennifer

2016-04-01

Long-term incidence of endocrine and exocrine insufficiency after pancreatectomy is poorly described. We analyze the long-term risks of pancreatic insufficiency after pancreatectomy. Subjects who underwent pancreatectomy from 2002 to 2012 were identified from a prospective database (n = 227). Subjects who underwent total pancreatectomy or pancreatitis surgery were excluded. New post-operative endocrine and exocrine insufficiency was defined as the need for new pharmacologic intervention within 1000 days from resection. 28 (16%) of 178 subjects without pre-existing endocrine insufficiency developed post-operative endocrine insufficiency: 7 (25%) did so within 30 days, 8 (29%) between 30 and 90 days, and 13 (46%) after 90 days. 94 (43%) of 214 subjects without pre-operative exocrine insufficiency developed exocrine insufficiency: 20 (21%) did so within 30 days, 29 (31%) between 30 and 90 days, and 45 (48%) after 90 days. Adjuvant radiation was associated with new endocrine insufficiency. On multivariate regression, pancreaticoduodenectomy and chemotherapy were associated with a greater risk of exocrine insufficiency. Reporting 30-day functional outcomes for pancreatic resection is insufficient, as nearly 45% of subjects who develop disease do so after 90 days. Reporting of at least 90-day outcomes may more reliably assess risk for post-operative endocrine and exocrine insufficiency. Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

Overview of the Pathophysiological Implications of Organotins on the Endocrine System.

PubMed

Marques, Vinicius Bermond; Faria, Rodrigo Alves; Dos Santos, Leonardo

2018-01-01

Organotins (OTs) are pollutants that are used widely by industry as disinfectants, pesticides, and most frequently as biocides in antifouling paints. This mini-review presents the main evidences from the literature about morphophysiological changes induced by OTs in the mammal endocrine system, focusing on the metabolism and reproductive control. Similar to other toxic compounds, the main effects with potential health risks to humans and experimental animals are not only related to dose and time of exposure but also to age, gender, and tissue/cell exposed. Regarding the underlying mechanisms, current literature indicates that OTs can directly damage endocrine glands, as well as interfere with neurohormonal control of endocrine function (i.e., in the hypothalamic-pituitary axis), altering hormone synthesis and/or bioavailability or activity of hormone receptors in the target cells. Importantly, OTs induces biochemical and morphological changes in gonads, abnormal steroidogenesis, both associated with reproductive dysfunctions such as irregular estrous cyclicity in female or spermatogenic disorders in male animals. Additionally, due to their role on endocrine systems predisposing to obesity, OTs are also included in the metabolism disrupting chemical hypothesis, either by central (e.g., accurate nucleus and lateral hypothalamus) or peripheral (e.g., adipose tissue) mechanisms. Thus, OTs should be indeed considered a major endocrine disruptor, being indispensable to understand the main toxic effects on the different tissues and its causative role for endocrine, metabolic, and reproductive dysfunctions observed.

Endocrine Dysfunction in Female FMR1 Premutation Carriers: Characteristics and Association with Ill Health

PubMed Central

Campbell, Sonya; Eley, Sarah E. A.; McKechanie, Andrew G.; Stanfield, Andrew C.

2016-01-01

Female FMR1 premutation carriers (PMC) have been suggested to be at greater risk of ill health, in particular endocrine dysfunction, compared to the general population. We set out to review the literature relating to endocrine dysfunction, including premature ovarian insufficiency (POI), in female PMCs, and then to consider whether endocrine dysfunction in itself may be predictive of other illnesses in female PMCs. A systematic review and pilot data from a semi-structured health questionnaire were used. Medline, Embase, and PsycInfo were searched for papers concerning PMCs and endocrine dysfunction. For the pilot study, self-reported diagnoses in females were compared between PMCs with endocrine dysfunction (n = 18), PMCs without endocrine dysfunction (n = 14), and individuals without the premutation (n = 15). Twenty-nine papers were identified in the review; the majority concerned POI and reduced fertility, which are consistently found to be more common in PMCs than controls. There was some evidence that thyroid dysfunction may occur more frequently in subgroups of PMCs and that those with endocrine difficulties have poorer health than those without. In the pilot study, PMCs with endocrine problems reported higher levels of fibromyalgia (p = 0.03), tremor (p = 0.03), headache (p = 0.01) and obsessive–compulsive disorder (p = 0.009) than either comparison group. Further larger scale research is warranted to determine whether female PMCs are at risk of endocrine disorders other than those associated with reproduction and whether endocrine dysfunction identifies a high-risk group for the presence of other health conditions. PMID:27869718

Adjuvant psychological therapy in long-term endocrine conditions.

PubMed

Daniels, J; Turner-Cobb, J M

2017-06-01

Consideration of psychological distress in long-term endocrine conditions is of vital importance given the prevalence of anxiety and depression in such disorders. Poor mental health can lead to compromised self-care, higher utilization of health services, lower rates of adherence, reduced quality of life and ultimately poorer outcomes. Adjuvant psychological therapy offers an effective resource to reduce distress in endocrine conditions. While the vast majority of work in this area has focused on psychological screening and intervention in diabetes, identification and recognition of psychological distress are equally important in other endocrinological conditions, with supportive evidence in polycystic ovary syndrome and Addison's disease. Referral pathways and recommendations set out by UK guidelines and the Department of Health mandate requires greater attention across a wider range of long-term endocrine conditions to facilitate improved quality of life and health outcome. © 2017 John Wiley & Sons Ltd.

How does obesity affect the endocrine system? A narrative review.

PubMed

Poddar, M; Chetty, Y; Chetty, V T

2017-06-01

Obesity is a chronic, relapsing medical condition that results from an imbalance of energy expenditure and consumption. It is a leading cause of preventable illness, disability and premature death. The causes of obesity are multifactorial and include behavioural, socioeconomic, genetic, environmental and psychosocial factors. Rarely are endocrine diseases, e.g., hypothyroidism or Cushing's syndrome, the cause of obesity. What is less understood is how obesity affects the endocrine system. In this review, we will discuss the impact of obesity on multiple endocrine systems, including the hypothalamic-pituitary axis, changes in vitamin D homeostasis, gender steroids and thyroid hormones. We will also examine the renin angiotensin aldosterone system and insulin pathophysiology associated with obesity. We will provide a general overview of the biochemical changes that can be seen in patients with obesity, review possible aetiologies of these changes and briefly consider current guidelines on their management. This review will not discuss endocrine causes of obesity. © 2017 World Obesity Federation.

The Cdk4-E2f1 pathway regulates early pancreas development by targeting Pdx1+ progenitors and Ngn3+ endocrine precursors

PubMed Central

Kim, So Yoon; Rane, Sushil G.

2011-01-01

Cell division and cell differentiation are intricately regulated processes vital to organ development. Cyclin-dependent kinases (Cdks) are master regulators of the cell cycle that orchestrate the cell division and differentiation programs. Cdk1 is essential to drive cell division and is required for the first embryonic divisions, whereas Cdks 2, 4 and 6 are dispensable for organogenesis but vital for tissue-specific cell development. Here, we illustrate an important role for Cdk4 in regulating early pancreas development. Pancreatic development involves extensive morphogenesis, proliferation and differentiation of the epithelium to give rise to the distinct cell lineages of the adult pancreas. The cell cycle molecules that specify lineage commitment within the early pancreas are unknown. We show that Cdk4 and its downstream transcription factor E2f1 regulate mouse pancreas development prior to and during the secondary transition. Cdk4 deficiency reduces embryonic pancreas size owing to impaired mesenchyme development and fewer Pdx1+ pancreatic progenitor cells. Expression of activated Cdk4R24C kinase leads to increased Nkx2.2+ and Nkx6.1+ cells and a rise in the number and proliferation of Ngn3+ endocrine precursors, resulting in expansion of the β cell lineage. We show that E2f1 binds and activates the Ngn3 promoter to modulate Ngn3 expression levels in the embryonic pancreas in a Cdk4-dependent manner. These results suggest that Cdk4 promotes β cell development by directing E2f1-mediated activation of Ngn3 and increasing the pool of endocrine precursors, and identify Cdk4 as an important regulator of early pancreas development that modulates the proliferation potential of pancreatic progenitors and endocrine precursors. PMID:21490060

Effects of alcohol on the endocrine system.

PubMed

Rachdaoui, Nadia; Sarkar, Dipak K

2013-09-01

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 physiologic 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. Copyright © 2013 Elsevier Inc. All rights reserved.

European endocrine surgery in the 150-year history of Langenbeck's Archives of Surgery.

PubMed

Dralle, Henning; Machens, A

2010-04-01

Founded in 1861 as a German language scientific forum of exchange for European surgeons, Langenbeck's Archives of Surgery quickly advanced to become the premier journal of thyroid surgery before World War I, serving as a point of crystallization for the emerging discipline of endocrine surgery. During the interwar period and, in particular, in the first decades after World War II, Langenbeck's Archives of Surgery lost its dominant position as an international and European medium of publication of top quality articles in the area of endocrine surgery. Nevertheless, the journal remained the chief publication organ of German language articles in the field of endocrine surgery. After a series of key events, Langenbeck's Archives of Surgery managed to reclaim its former position as the leading European journal of endocrine surgery: (1) the formation of endocrine surgery in the early 1980s as a subdiscipline of general and visceral surgery; (2) the change of the language of publication from German to English in 1998; and (3) the journal's appointment in 2004 as the official organ of publication of the European Society of Endocrine Surgeons. All in all, the 150-year publication record of Langenbeck's Archives of Surgery closely reflects the history of European Endocrine Surgery. Following the path of seminal articles from Billroth, Kocher, and many other surgical luminaries published in the journal more than 100 years ago, Langenbeck's Archives of Surgery today stands out as the principal European journal in the field of endocrine surgery.

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)

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. ...

ENDOCRINE DISRUPTORS AS A THREAT TO NEUROLOGICAL FUNCTION

PubMed Central

Weiss, Bernard

2011-01-01

Endocrine disruption is a concept and principle whose origins can be traced to the beginnings of the environmental movement in the 1960s. It began with puzzlement about and the flaring of research on the decline of wildlife, particularly avian species. The proposed causes accented pesticides, especially persistent organochlorines such as DDT. Its scope gradually widened beyond pesticides, and, as endocrine disruption offered an explanation for the wildlife phenomena, it seemed to explain, as well, changes in fertility and disorders of male reproduction such as testicular cancer. Once disturbed gonadal hormone function became the most likely explanation, it provoked other questions. The most challenging arose because of how critical gonadal hormones are to brain function, especially as determinants of brain sexual differentiation. Pursuit of such connections has generated a robust literature embracing a broad swath of chemical classes. How endocrine disrupting chemicals influence the adult and aging brain is a question, so far mostly ignored because of the emphasis on early development, that warrants vigorous investigation. Gonadal hormones are crucial to optimal brain function during maturity and even senescence. They are pivotal to the processes of neurogenesis. They exert protective actions against neurodegenerative disorders such as dementia and support smoothly functioning cognitive activities. The limited research conducted so far on endocrine disruptors, aging, and neurogenesis argues that they should be overlooked no longer. PMID:21474148

The endocrine manifestations of anorexia nervosa: mechanisms and management.

PubMed

Schorr, Melanie; Miller, Karen K

2017-03-01

Anorexia nervosa is a psychiatric disorder characterized by altered body image, persistent food restriction and low body weight, and is associated with global endocrine dysregulation in both adolescent girls and women. Dysfunction of the hypothalamic-pituitary axis includes hypogonadotropic hypogonadism with relative oestrogen and androgen deficiency, growth hormone resistance, hypercortisolaemia, non-thyroidal illness syndrome, hyponatraemia and hypooxytocinaemia. Serum levels of leptin, an anorexigenic adipokine, are suppressed and levels of ghrelin, an orexigenic gut peptide, are elevated in women with anorexia nervosa; however, levels of peptide YY, an anorexigenic gut peptide, are paradoxically elevated. Although most, but not all, of these endocrine disturbances are adaptive to the low energy state of chronic starvation and reverse with treatment of the eating disorder, many contribute to impaired skeletal integrity, as well as neuropsychiatric comorbidities, in individuals with anorexia nervosa. Although 5-15% of patients with anorexia nervosa are men, only limited data exist regarding the endocrine impact of the disease in adolescent boys and men. Further research is needed to understand the endocrine determinants of bone loss and neuropsychiatric comorbidities in anorexia nervosa in both women and men, as well as to formulate optimal treatment strategies.

Cosmetics as endocrine disruptors: are they a health risk?

PubMed

Nicolopoulou-Stamati, Polyxeni; Hens, Luc; Sasco, Annie J

2015-12-01

Exposure to chemicals from different sources in everyday life is widespread; one such source is the wide range of products listed under the title "cosmetics", including the different types of popular and widely-advertised sunscreens. Women are encouraged through advertising to buy into the myth of everlasting youth, and one of the most alarming consequences is in utero exposure to chemicals. The main route of exposure is the skin, but the main endpoint of exposure is endocrine disruption. This is due to many substances in cosmetics and sunscreens that have endocrine active properties which affect reproductive health but which also have other endpoints, such as cancer. Reducing the exposure to endocrine disruptors is framed not only in the context of the reduction of health risks, but is also significant against the background and rise of ethical consumerism, and the responsibility of the cosmetics industry in this respect. Although some plants show endocrine-disrupting activity, the use of well-selected natural products might reduce the use of synthetic chemicals. Instruments dealing with this problem include life-cycle analysis, eco-design, and green labels; in combination with the committed use of environmental management systems, they contribute to "corporate social responsibility".

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

Prevention of nosocomial infection in cardiac surgery by decontamination of the nasopharynx and oropharynx with chlorhexidine gluconate: a randomized controlled trial.

PubMed

Segers, Patrique; Speekenbrink, Ron G H; Ubbink, Dirk T; van Ogtrop, Marc L; de Mol, Bas A

2006-11-22

Nosocomial infections are an important cause of morbidity and mortality after cardiac surgery. Decolonization of endogenous potential pathogenic microorganisms is important in the prevention of nosocomial infections. To determine the efficacy of perioperative decontamination of the nasopharynx and oropharynx with 0.12% chlorhexidine gluconate for reduction of nosocomial infection after cardiac surgery. A prospective, randomized, double-blind, placebo-controlled clinical trial conducted at the Onze Lieve Vrouwe Gasthuis, Amsterdam, the Netherlands, between August 1, 2003, and September 1, 2005. Of 991 patients older than 18 years undergoing elective cardiothoracic surgery during the study interval, 954 were eligible for analysis. Oropharyngeal rinse and nasal ointment containing either chlorhexidine gluconate or placebo. Incidence of nosocomial infection, in addition to the rate of Staphylococcus aureus nasal carriage and duration of hospital stay. The incidence of nosocomial infection in the chlorhexidine gluconate group and placebo group was 19.8% and 26.2%, respectively (absolute risk reduction [ARR], 6.4%; 95% confidence interval [CI], 1.1%-11.7%; P = .002). In particular, lower respiratory tract infections and deep surgical site infections were less common in the chlorhexidine gluconate group than in the placebo group (ARR, 6.5%; 95% CI, 2.3%-10.7%; P = .002; and 3.2%; 95% CI, 0.9%-5.5%; P = .002, respectively). For the prevention of 1 nosocomial infection, 16 patients needed to be treated with chlorhexidine gluconate. A significant reduction of 57.5% in S aureus nasal carriage was found in the chlorhexidine gluconate group compared with a reduction of 18.1% in the placebo group (P<.001). Total hospital stay for patients treated with chlorhexidine gluconate was 9.5 days compared with 10.3 days in the placebo group (ARR, 0.8 days; 95% CI, 0.24-1.88; P = .04). Decontamination of the nasopharynx and oropharynx with chlorhexidine gluconate appears to be an

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

Expert consensus of general surgery residents' proficiency with common endocrine operations.

PubMed

Phitayakorn, Roy; Kelz, Rachel R; Petrusa, Emil; Sippel, Rebecca S; Sturgeon, Cord; Patel, Kepal N; Perrier, Nancy D

2017-01-01

Proficiency with common endocrine operations is expected of graduating, general surgery residents. However, no expert consensus guidelines exist about these expectations. Members of the American Association of Endocrine Surgeons were surveyed about their opinions on resident proficiency with common endocrine operations. Overall response rate was 38%. A total of 92% of the respondents operate with residents. On average, they believed that the steps of a total thyroidectomy for benign disease and a well-localized parathyroidectomy could be performed by a postgraduate year 4 surgery resident. Specific steps that they thought might require more training included decisions to divide the strap muscles or leaving a drain. Approximately 66% of respondents thought that a postgraduate year 5 surgery resident could independently perform a total thyroidectomy for benign disease, but only 45% felt similarly for malignant thyroid disease; 79% thought that a postgraduate year 5 surgery resident could independently perform a parathyroidectomy. Respondents' years of experience correlated with their opinions about resident autonomy for total thyroidectomy (benign r = 0.38, P < .001; malignant r = 0.29, P = .001) but not parathyroidectomy. On multivariate analysis, sex and years of experience of the respondents were independently associated with opinions on autonomy but only for total thyroidectomy for benign disease (P = .001). Annual endocrine volume of the respondents did not correlate with beliefs in autonomy. There was general agreement among responding members of the AAES about resident proficiency and autonomy with common endocrine operations. As postgraduate year 5 residents may not be proficient in advanced endocrine operations, opportunities exist to improve training prior to the transition to independent practice for graduates that anticipate performing endocrine operations routinely. Copyright © 2016 Elsevier Inc. All rights reserved.

Overview of the Pathophysiological Implications of Organotins on the Endocrine System

PubMed Central

Marques, Vinicius Bermond; Faria, Rodrigo Alves; Dos Santos, Leonardo

2018-01-01

Organotins (OTs) are pollutants that are used widely by industry as disinfectants, pesticides, and most frequently as biocides in antifouling paints. This mini-review presents the main evidences from the literature about morphophysiological changes induced by OTs in the mammal endocrine system, focusing on the metabolism and reproductive control. Similar to other toxic compounds, the main effects with potential health risks to humans and experimental animals are not only related to dose and time of exposure but also to age, gender, and tissue/cell exposed. Regarding the underlying mechanisms, current literature indicates that OTs can directly damage endocrine glands, as well as interfere with neurohormonal control of endocrine function (i.e., in the hypothalamic–pituitary axis), altering hormone synthesis and/or bioavailability or activity of hormone receptors in the target cells. Importantly, OTs induces biochemical and morphological changes in gonads, abnormal steroidogenesis, both associated with reproductive dysfunctions such as irregular estrous cyclicity in female or spermatogenic disorders in male animals. Additionally, due to their role on endocrine systems predisposing to obesity, OTs are also included in the metabolism disrupting chemical hypothesis, either by central (e.g., accurate nucleus and lateral hypothalamus) or peripheral (e.g., adipose tissue) mechanisms. Thus, OTs should be indeed considered a major endocrine disruptor, being indispensable to understand the main toxic effects on the different tissues and its causative role for endocrine, metabolic, and reproductive dysfunctions observed. PMID:29615977

Pesticides as endocrine-disrupting chemicals

EPA Science Inventory

Pesticides are designed to be bioactive against certain targets but can cause toxicity to nontarget species by a variety of other modes of action including disturbance of endocrine function. As such, pesticides have been found to bind and alter the function of hormone receptors, ...

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

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. Copyright © 2012 Elsevier Inc. All rights reserved.

Endocrine disrupting effects of butylated hydroxyanisole (BHA - E320)

PubMed Central

POP, ANCA; KISS, BELA; LOGHIN, FELICIA

2013-01-01

Butylated hydroxyanisole (BHA) is extensively used as antioxidant in foods, food packaging, cosmetics and pharmaceuticals. In the past years, it raised concerns regarding its possible endocrine disrupting effect. The existing in vitro studies indicate that BHA presents a weak estrogenic effect and also anti-androgenic properties while an in vivo study found it to have antiestrogenic properties. There is no sufficient data available at the moment to draw a conclusion regarding the safety of BHA when referring to its endocrine disrupting effect. Since a fraction of the population might be exposed to doses superior to the acceptable daily intake (ADI), it is important to gather more in vitro and in vivo data concerning the potential effects that BHA might have alone, but also in mixtures with natural hormones or other endocrine disrupting compounds. PMID:26527908

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.

The Heart of the Matter: Cardiac Manifestations of Endocrine Disease

PubMed Central

Binu, Aditya John; Cherian, Kripa Elizabeth; Kapoor, Nitin; Chacko, Sujith Thomas; George, Oommen; Paul, Thomas Vizhalil

2017-01-01

Endocrine disorders manifest as a disturbance in the milieu of multiple organ systems. The cardiovascular system may be directly affected or alter its function to maintain the state of homeostasis. In this article, we aim to review the pathophysiology, diagnosis, clinical features and management of cardiac manifestations of various endocrine disorders. PMID:29285459

Familial endocrine myxolentiginosis.

PubMed

Panossian, D H; Marais, G E; Marais, H J

1995-11-01

We present an unusual case of a left atrial myxoma as a feature of a familial mesoectodermal disorder and review the literature. The new term "familial endocrine myxolentiginosis" is proposed, which is descriptive of the major clinical components of the syndrome. Myriad features of this disorder include (1) cardiac myxomas; (2) cutaneous myxomas; (3) multiple lentigines or blue nevi, particularly of the head and neck; (4) bilateral primary pigmented nodular adrenocortical hyperplasia; (5) unusual testicular tumors; (6) pituitary tumors; (7) myxoid fibroadenomas of the breast; (8) myxomatous disorder of the stroma of the breast; (9) ductal adenoma of the breast; and (10) psammomatous melanotic schwannoma. A tentative diagnosis is suggested by identifying two features and a definitive diagnosis is made by three or more features. The clinical and pathologic features of cardiac myxoma in familial endocrine myxolentiginosis are identical to those of familial cardiac myxoma: age < 40 years, atypical locations, multicentric origins, and recurrent presentations. A Venn diagram classification for cardiac myxomas is proposed. We include photographic, echocardiographic, biopsy, and adrenal computerized tomography documentation in our patient. Recognition of this disorder is important because of its clinical, surgical, and genetic implications. The availability of transesophageal echocardiographic technology should allow early diagnosis of this underdiagnosed entity. Clinicians should consider this entity in the differential diagnosis of their patients with any one of these manifestations.

Genetics of Endocrine and Neuroendocrine Neoplasias (PDQ®)—Health Professional Version

Cancer.gov

Genetics of Endocrine and Neuroendocrine Neoplasias discusses inherited syndromes multiple endocrine neoplasia types 1, 2, and 4 (MEN1, MEN2, MEN4), familial pheochromocytoma and paraganglioma, Carney-Stratakis syndrome, and familial nonmedullary thyroid cancer. Learn more in this clinician summary.

Biological Profiling of Endocrine Related Effects of Chemicals in ToxCast

EPA Science Inventory

The Food Quality Protection Act of 1996 mandates that EPA implement a validated screening program for detecting estrogenic chemicals, as well as other endocrine targets deemed appropriate by the Administrator. EPA’s Endocrine Disruptor Screening Program (EDSP) has been developing...

Biological Profiling of Endocrine Related Effects of Chemicals Using ToxCast

EPA Science Inventory

The Food Quality Protection Act of 1996 mandates that EPA implement a validated screening program for detecting estrogenic chemicals, as well as other endocrine targets deemed appropriate by the Administrator. EPA’s Endocrine Disruptor Screening Program (EDSP) has been developing...

Hedgehog signaling: endocrine gland development and function.

PubMed

Cohen, M Michael

2010-01-01

The role of hedgehog signaling is analyzed in relation to the developing endocrine glands: pituitary, ovary, testis, adrenal cortex, pancreas, prostate, and epiphyseal growth. Experimental and pathological correlates of these organs are also discussed. The second section addresses a number of topics. First, the pituitary gland, no matter how hypoplastic, is present in most cases of human holoprosencephaly, unlike animals in which it is always said to be absent. The difference appears to be that animal mutations and teratogenic models involve both copies of the gene in question, whereas in humans the condition is most commonly heterozygous. Second, tests of endocrine function are not reported with great frequency, and an early demise in severe cases of holoprosencephaly accounts for this trend. Reported tests of endocrine function are reviewed. Third, diabetes insipidus has been recorded in a number of cases of holoprosencephaly. Its frequency is unknown because it could be masked by adrenal insufficiency in some cases and may not be recognized in others. Because of the abnormal hypothalamic-infundibular region in holoprosencephaly, diabetes insipidus could be caused by a defect in the supra-optic or paraventricular hypothalamic nuclei or in release of ADH via the infundibulum and posterior pituitary.

Pernicious anaemia and mucosal endocrine cell proliferation of the non-antral stomach.

PubMed Central

Rode, J; Dhillon, A P; Papadaki, L; Stockbrügger, R; Thompson, R J; Moss, E; Cotton, P B

1986-01-01

There is a recognised association between pernicious anaemia and the development of gastric carcinoma, endocrine cell hyperplasia, and carcinoid tumour. Multiple endoscopic biopsies from the body mucosa of seven patients with pernicious anaemia showed small intestinal metaplasia with varying degrees of inflammation, fibrosis, and expansion of the lamina propria. Using conventional silver and lead stains, endocrine cells were inconspicuous. Staining for the general neural and neuroendocrine markers NSE and PGP 9.5 revealed a proliferation of endocrine cells in the epithelium and isolated clumps of endocrine cells in the lamina propria. The clumps were composed of two cell types, either small or large. Some of these endocrine cells showed gastrin, 5HT, VIP and substance P immunoreactivity of varying intensity. Ultrastructurally nine morphologically distinct types of granules were found some of which correlated with the immunohistochemistry. Some separate islands were composed solely of endocrine cells while others had a definite neural component, suggesting that the former arise from 'budding off' of enteroendocrine cells and the latter originate from the neuroendocrine cells of the lamina propria plexus. Thus there may be a dual origin of carcinoid tumours. Carcinoid tumours associated with pernicious anaemia tend to be multifocal and are infrequent. Less than 50 such cases have hitherto been reported. Our findings of endocrine cells proliferations in seven cases of pernicious anaemia indicate that this may be an adaptive change that occurs frequently and provides the basis on which carcinoids, less frequently, develop. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:3525338

Endocannabinoids and the Endocrine System in Health and Disease.

PubMed

Hillard, Cecilia J

2015-01-01

Some of the earliest reports of the effects of cannabis consumption on humans were related to endocrine system changes. In this review, the effects of cannabinoids and the role of the CB1 cannabinoid receptor in the regulation of the following endocrine systems are discussed: the hypothalamic-pituitary-gonadal axis, prolactin and oxytocin, thyroid hormone and growth hormone, and the hypothalamic-pituitary-adrenal axis. Preclinical and human study results are presented.

Introduction to the Endocrine System

MedlinePlus

... by downloading the Hormone Health Network's 3D Patient Education mobile app ! The endocrine system is a series of glands that produce and ... Network partners with other organizations to further patient education on hormone related issues. Network Sponsors The Hormone Health ... Disrupting Chemicals (EDCs) Steroid and Hormone ...

Embryonic transcription factor SOX9 drives breast cancer endocrine resistance.

PubMed

Jeselsohn, Rinath; Cornwell, MacIntosh; Pun, Matthew; Buchwalter, Gilles; Nguyen, Mai; Bango, Clyde; Huang, Ying; Kuang, Yanan; Paweletz, Cloud; Fu, Xiaoyong; Nardone, Agostina; De Angelis, Carmine; Detre, Simone; Dodson, Andrew; Mohammed, Hisham; Carroll, Jason S; Bowden, Michaela; Rao, Prakash; Long, Henry W; Li, Fugen; Dowsett, Mitchell; Schiff, Rachel; Brown, Myles

2017-05-30

The estrogen receptor (ER) drives the growth of most luminal breast cancers and is the primary target of endocrine therapy. Although ER blockade with drugs such as tamoxifen is very effective, a major clinical limitation is the development of endocrine resistance especially in the setting of metastatic disease. Preclinical and clinical observations suggest that even following the development of endocrine resistance, ER signaling continues to exert a pivotal role in tumor progression in the majority of cases. Through the analysis of the ER cistrome in tamoxifen-resistant breast cancer cells, we have uncovered a role for an RUNX2-ER complex that stimulates the transcription of a set of genes, including most notably the stem cell factor SOX9, that promote proliferation and a metastatic phenotype. We show that up-regulation of SOX9 is sufficient to cause relative endocrine resistance. The gain of SOX9 as an ER-regulated gene associated with tamoxifen resistance was validated in a unique set of clinical samples supporting the need for the development of improved ER antagonists.

Embryonic transcription factor SOX9 drives breast cancer endocrine resistance

PubMed Central

Jeselsohn, Rinath; Cornwell, MacIntosh; Pun, Matthew; Buchwalter, Gilles; Nguyen, Mai; Bango, Clyde; Huang, Ying; Kuang, Yanan; Paweletz, Cloud; Fu, Xiaoyong; Nardone, Agostina; De Angelis, Carmine; Detre, Simone; Dodson, Andrew; Mohammed, Hisham; Carroll, Jason S.; Bowden, Michaela; Rao, Prakash; Long, Henry W.; Li, Fugen; Dowsett, Mitchell; Schiff, Rachel; Brown, Myles

2017-01-01

The estrogen receptor (ER) drives the growth of most luminal breast cancers and is the primary target of endocrine therapy. Although ER blockade with drugs such as tamoxifen is very effective, a major clinical limitation is the development of endocrine resistance especially in the setting of metastatic disease. Preclinical and clinical observations suggest that even following the development of endocrine resistance, ER signaling continues to exert a pivotal role in tumor progression in the majority of cases. Through the analysis of the ER cistrome in tamoxifen-resistant breast cancer cells, we have uncovered a role for an RUNX2–ER complex that stimulates the transcription of a set of genes, including most notably the stem cell factor SOX9, that promote proliferation and a metastatic phenotype. We show that up-regulation of SOX9 is sufficient to cause relative endocrine resistance. The gain of SOX9 as an ER-regulated gene associated with tamoxifen resistance was validated in a unique set of clinical samples supporting the need for the development of improved ER antagonists. PMID:28507152

Short-term exposure of arsenite disrupted thyroid endocrine system and altered gene transcription in the HPT axis in zebrafish.

PubMed

Sun, Hong-Jie; Li, Hong-Bo; Xiang, Ping; Zhang, Xiaowei; Ma, Lena Q

2015-10-01

Arsenic (As) pollution in aquatic environment may adversely impact fish health by disrupting their thyroid hormone homeostasis. In this study, we explored the effect of short-term exposure of arsenite (AsIII) on thyroid endocrine system in zebrafish. We measured As concentrations, As speciation, and thyroid hormone thyroxine levels in whole zebrafish, oxidative stress (H2O2) and damage (MDA) in the liver, and gene transcription in hypothalamic-pituitary-thyroid (HPT) axis in the brain and liver tissues of zebrafish after exposing to different AsIII concentrations for 48 h. Result indicated that exposure to AsIII increased inorganic As in zebrafish to 0.46-0.72 mg kg(-1), induced oxidative stress with H2O2 being increased by 1.4-2.5 times and caused oxidative damage with MDA being augmented by 1.6 times. AsIII exposure increased thyroxine levels by 1.3-1.4 times and modulated gene transcription in HPT axis. Our study showed AsIII caused oxidative damage, affected thyroid endocrine system and altered gene transcription in HPT axis in zebrafish. Published by Elsevier Ltd.

Endocrine therapy use among elderly hormone receptor-positive breast cancer patients enrolled in Medicare Part D

PubMed Central

Riley, Gerald F.; Warren, Joan L.; Harlan, Linda C.; Blackwell, Steven A.

2011-01-01

Background Clinical guidelines recommend that women with hormone-receptor positive breast cancer receive endocrine therapy (selective estrogen receptor modulators [SERMs] or aromatase inhibitors [AIs]) for five years following diagnosis. Objective To examine utilization and adherence to therapy for SERMs and AIs in Medicare Part D prescription drug plans. Data Linked Surveillance, Epidemiology, and End Results (SEER)-Medicare data. Study design We identified 15,542 elderly women diagnosed with hormone-receptor positive breast cancer in years 2003-2005 (the latest SEER data at the time of the study) and enrolled in a Part D plan in 2006 or 2007 (the initial years of Part D). This permitted us to compare utilization and adherence to therapy at various points within the recommended five-year timeframe for endocrine therapy. SERM and AI use was measured from claim records. Non-adherence to therapy was defined as a medication possession ratio of less than 80 percent. Principal findings Between May 2006 and December 2007, 22 percent of beneficiaries received SERM, 52 percent AI, and 26 percent received neither. The percent receiving any endocrine therapy decreased with time from diagnosis. Among SERM and AI users, 20-30 percent were non-adherent to therapy; out-of-pocket costs were higher for AI than SERM and were strongly associated with non-adherence. For AI users without a low income subsidy, adherence to therapy deteriorated after reaching the Part D coverage gap. Conclusions Many elderly breast cancer patients were not receiving therapy for the recommended five years following diagnosis. Choosing a Part D plan that minimizes out-of-pocket costs is critical to ensuring beneficiary access to essential medications. PMID:22340780

Attitude of medical students towards Early Clinical Exposure in learning endocrine physiology

PubMed Central

Sathishkumar, Solomon; Thomas, Nihal; Tharion, Elizabeth; Neelakantan, Nithya; Vyas, Rashmi

2007-01-01

Background Different teaching-learning methods have been used in teaching endocrine physiology for the medical students, so as to increase their interest and enhance their learning. This paper describes the pros and cons of the various approaches used to reinforce didactic instruction in endocrine physiology and goes on to describe the value of adding an Early Clinical Exposure program (ECE) to didactic instruction in endocrine physiology, as well as student reactions to it as an alternative approach. Discussion Various methods have been used to reinforce didactic instruction in endocrine physiology such as case-stimulated learning, problem-based learning, patient-centred learning and multiple-format sessions. We devised a teaching-learning intervention in endocrine physiology, which comprised of traditional didactic lectures, supplemented with an ECE program consisting of case based lectures and a hospital visit to see patients. A focus group discussion was conducted with the medical students and, based on the themes that emerged from it, a questionnaire was developed and administered to further enquire into the attitude of all the students towards ECE in learning endocrine physiology. The students in their feedback commented that ECE increased their interest for the subject and motivated them to read more. They also felt that ECE enhanced their understanding of endocrine physiology, enabled them to remember the subject better, contributed to their knowledge of the subject and also helped them to integrate their knowledge. Many students said that ECE increased their sensitivity toward patient problems and needs. They expressed a desire and a need for ECE to be continued in teaching endocrine physiology for future groups of students and also be extended for teaching other systems as well. The majority of the students (96.4%) in their feedback gave an overall rating of the program as good to excellent on a 5 point Likert scale. Summary The ECE program was introduced

Requirement for Pdx1 in specification of latent endocrine progenitors in zebrafish

PubMed Central

2011-01-01

Background Insulin-producing beta cells emerge during pancreas development in two sequential waves. Recently described later-forming beta cells in zebrafish show high similarity to second wave mammalian beta cells in developmental capacity. Loss-of-function studies in mouse and zebrafish demonstrated that the homeobox transcription factors Pdx1 and Hb9 are both critical for pancreas and beta cell development and discrete stage-specific requirements for these genes have been uncovered. Previously, exocrine and endocrine cell recovery was shown to follow loss of pdx1 in zebrafish, but the progenitor cells and molecular mechanisms responsible have not been clearly defined. In addition, interactions of pdx1 and hb9 in beta cell formation have not been addressed. Results To learn more about endocrine progenitor specification, we examined beta cell formation following morpholino-mediated depletion of pdx1 and hb9. We find that after early beta cell reduction, recovery occurs following loss of either pdx1 or hb9 function. Unexpectedly, simultaneous knockdown of both hb9 and pdx1 leads to virtually complete and persistent beta cell deficiency. We used a NeuroD:EGFP transgenic line to examine endocrine cell behavior in vivo and developed a novel live-imaging technique to document emergence and migration of late-forming endocrine precursors in real time. Our data show that Notch-responsive progenitors for late-arising endocrine cells are predominantly post mitotic and depend on pdx1. By contrast, early-arising endocrine cells are specified and differentiate independent of pdx1. Conclusions The nearly complete beta cell deficiency after combined loss of hb9 and pdx1 suggests functional cooperation, which we clarify as distinct roles in early and late endocrine cell formation. A novel imaging approach permitted visualization of the emergence of late endocrine cells within developing embryos for the first time. We demonstrate a pdx1-dependent progenitor population essential for

Risk factors for oropharynx cancer in a cohort of HIV-infected veterans.

PubMed

Chew, Erin Y; Hartman, Christine M; Richardson, Peter A; Zevallos, Jose P; Sikora, Andrew G; Kramer, Jennifer R; Chiao, Elizabeth Y

2017-05-01

To evaluate HIV-related and other clinical risk factors associated with oropharynx cancer (OPSCC) in HIV-infected U.S. Veterans. Retrospective cohort study utilizing Veterans Affairs HIV Clinical Case Registry (CCR) data from 1985 to 2010. Outcome was incident OPSCC as indicated by 1 inpatient or 2 outpatient ICD-9 codes. Cox proportional hazard models were used to determine hazard ratios (HR) and 95% confidence intervals (CI) for each risk factor on the time to OPSCC diagnosis. A total of 40,996 HIV-infected male veterans were included in the cohort with 97 cases of OPSCC. The age adjusted incidence rate was 23.2/100,000 [95% CI 17.8-29.2]. Age>50 (aHR=3.8, 95% CI 1.9-7.8), recent CD4<200 (aHR=3.8, 95% CI 2.0-7.3), and undetectable HIV viral loads 40-79% of the time (aHR=1.8, 95% CI 1.1-3.0) were associated with an increased risk of OPSCC. Era of HIV diagnosis, utilization of cART, nadir CD4 count, race, smoking history, and previous risk of HPV disease, including condyloma or invasive squamous cell carcinoma of the anus (SCCA) were not associated with increased risk of OPSCC. Patients who were older at beginning of follow up, had lower CD4 counts around the time of OPSCC diagnosis, and moderate HIV viral control during follow-up had an increased risk of OPSCC. Other HPV-related diseases such as SCCA and condyloma did not increase the risk for OPSCC. Copyright © 2017 Elsevier Ltd. All rights reserved.

The impact of opioids on the endocrine system.

PubMed

Katz, Nathaniel; Mazer, Norman A

2009-02-01

Opioids have been used for medicinal and analgesic purposes for centuries. However, their negative effects on the endocrine system, which have been known for some times, are barely discussed in modern medicine. Therefore, we conducted a systematic review of the impact of opioids on the endocrine system. A review of the English language literature on preclinical and clinical studies of any type on the influence of opioids on the endocrine system was conducted. Preliminary recommendations for monitoring and managing these problems were provided. Long-term opioid therapy for either addiction or chronic pain often induces hypogonadism owing to central suppression of hypothalamic secretion of gonadotropin-releasing hormone. Symptoms of opioid-induced hypogonadism include loss of libido, infertility, fatigue, depression, anxiety, loss of muscle strength and mass, osteoporosis, and compression fractures in both men and women; impotence in men; and menstrual irregularities and galactorrhea in women. In view of the increased use of opioids for chronic pain, it has become increasingly important to monitor patients taking opioids and manage endocrine complications. Therefore, patients on opioid therapy should be routinely screened for such symptoms and for laboratory abnormalities in sex hormones. Opioid-induced hypogonadism seems to be a common complication of therapeutic or illicit opioid use. Patients on long-term opioid therapy should be prospectively monitored, and in cases of opioid-induced hypogonadism, we recommend nonopioid pain management, opioid rotation, or sex hormone supplementation after careful consideration of the risks and benefits.

Bisphenol A and its analogs: Do their metabolites have endocrine activity?

PubMed

Gramec Skledar, Darja; Peterlin Mašič, Lucija

2016-10-01

Structural analogs of bisphenol A are commonly used as its alternatives in industrial and commercial applications. Nevertheless, the question arises whether the use of other bisphenols is justified as replacements for bisphenol A in mass production of plastic materials. To evaluate the influence of metabolic reactions on endocrine activities of bisphenols, we conducted a systematic review of the literature. Knowledge about the metabolic pathways and enzymes involved in metabolic biotransformations is essential for understanding and predicting mechanisms of toxicity. Bisphenols are metabolized predominantly by the glucuronidation reaction, which is considered their most important detoxification pathway, as based on current knowledge, glucuronides do not have activity on endocrine receptors. In contrast, several oxidative metabolites of bisphenols with enhanced endocrine activities are presented, and these findings indicate that oxidative metabolites of bisphenols can still have endocrine activities in humans. Copyright © 2016 Elsevier B.V. All rights reserved.

Muscular Dystrophies at Different Ages: Metabolic and Endocrine Alterations

PubMed Central

Cruz Guzmán, Oriana del Rocío; Chávez García, Ana Laura; Rodríguez-Cruz, Maricela

2012-01-01

Common metabolic and endocrine alterations exist across a wide range of muscular dystrophies. Skeletal muscle plays an important role in glucose metabolism and is a major participant in different signaling pathways. Therefore, its damage may lead to different metabolic disruptions. Two of the most important metabolic alterations in muscular dystrophies may be insulin resistance and obesity. However, only insulin resistance has been demonstrated in myotonic dystrophy. In addition, endocrine disturbances such as hypogonadism, low levels of testosterone, and growth hormone have been reported. This eventually will result in consequences such as growth failure and delayed puberty in the case of childhood dystrophies. Other consequences may be reduced male fertility, reduced spermatogenesis, and oligospermia, both in childhood as well as in adult muscular dystrophies. These facts all suggest that there is a need for better comprehension of metabolic and endocrine implications for muscular dystrophies with the purpose of developing improved clinical treatments and/or improvements in the quality of life of patients with dystrophy. Therefore, the aim of this paper is to describe the current knowledge about of metabolic and endocrine alterations in diverse types of dystrophinopathies, which will be divided into two groups: childhood and adult dystrophies which have different age of onset. PMID:22701119

Proceedings of the 1973 Lyndon B. Johnson Space Center Endocrine Program Conference

NASA Technical Reports Server (NTRS)

1975-01-01

Papers given at the conference are presented. Subjects covered include the following: biochemical changes during 28 days of space flight, modulating the pituitary-adrenal response to stress, the significance of biorhythms in space flight, the importance of the rein-angiotensin system in normal cardiovascular homeostasis, a progress report of stress-induced changes in corticosteroid metabolism, recent studies of physiological factors involved in the regulation of serotonin content and turnover in the brain, the role of brain biogenic amines in the control of pituitary-adrenocortical activity, application of the water immersion model to man by studies of acid-base homeostasis during simulated weightlessness, the present status of physiological studies and analysis of calcium homeostasis in the Apollo and Skylab programs, and endocrine considerations in the red-cell-mass and plasma-volume changes of Skylab 2 and 3 crews.

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

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

PHEOCHROMOCYTOMA: AN ENDOCRINE STRESS MIMICKING DISORDER

PubMed Central

Kantorovich, Vitaly; Eisenhofer, Graeme; Pacak, Karel

2008-01-01

Pheochromocytoma is an endocrine tumor that can uniquely mimic numerous stress-associated disorders, with variations in clinical manifestations resulting from different patterns of catecholamine secretion and actions of released catecholamines on physiological systems. PMID:19120142

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.

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 ...

Feedback control of growth, differentiation, and morphogenesis of pancreatic endocrine progenitors in an epithelial plexus niche

PubMed Central

Bankaitis, Eric D.; Bechard, Matthew E.; Wright, Christopher V.E.

2015-01-01

In the mammalian pancreas, endocrine cells undergo lineage allocation upon emergence from a bipotent duct/endocrine progenitor pool, which resides in the “trunk epithelium.” Major questions remain regarding how niche environments are organized within this epithelium to coordinate endocrine differentiation with programs of epithelial growth, maturation, and morphogenesis. We used EdU pulse-chase and tissue-reconstruction approaches to analyze how endocrine progenitors and their differentiating progeny are assembled within the trunk as it undergoes remodeling from an irregular plexus of tubules to form the eventual mature, branched ductal arbor. The bulk of endocrine progenitors is maintained in an epithelial “plexus state,” which is a transient intermediate during epithelial maturation within which endocrine cell differentiation is continually robust and surprisingly long-lived. Within the plexus, local feedback effects derived from the differentiating and delaminating endocrine cells nonautonomously regulate the flux of endocrine cell birth as well as proliferative growth of the bipotent cell population using Notch-dependent and Notch-independent influences, respectively. These feedback effects in turn maintain the plexus state to ensure prolonged allocation of endocrine cells late into gestation. These findings begin to define a niche-like environment guiding the genesis of the endocrine pancreas and advance current models for how differentiation is coordinated with the growth and morphogenesis of the developing pancreatic epithelium. PMID:26494792

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. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Screening for secondary endocrine hypertension in young patients.

PubMed

Trifanescu, Raluca; Carsote, Mara; Caragheorgheopol, Andra; Hortopan, Dan; Dumitrascu, Anda; Dobrescu, Mariana; Poiana, Catalina

2013-06-01

Secondary endocrine hypertension accounts for 5-12% of hypertension's causes. In selected patients (type 2 diabetes mellitus, sleep apnea syndrome with resistant hypertension, sudden deterioration in hypertension control), prevalence could be higher. To present etiology of endocrine secondary hypertension in a series of patients younger than 40 years at hypertension's onset. Medical records of 80 patients (39M/41F), aged 30.1 ± 8.2 years (range: 12-40 years), with maximum systolic blood pressure=190.4 ± 29.2 mm Hg, range: 145-300 mm Hg, maximum diastolic blood pressure=107.7 ± 16.9 mm Hg, range: 80-170 mm Hg) referred by cardiologists for endocrine hypertension screening were retrospectively reviewed. Cardiac and renal causes of secondary hypertension were previously excluded. In all patients, plasma catecholamines were measured by ELISA and plasma cortisol by immunochemiluminescence. Orthostatic aldosterone (ELISA) and direct renin (chemiluminescence) were measured in 48 patients. Secondary endocrine hypertension was confirmed in 16 out of 80 patients (20%). Primary hyperaldosteronism was diagnosed in 7 (4M/3F) out of 48 screened patients (14.6%). i.e. 8.75% from whole group: 5 patients with adrenal tumors (3 left/2 right), 2 patients with bilateral adrenal hyperplasia; all patients were hypokalemic at diagnostic (average nadir K+ levels = 2.5 ± 0.5 mmol/L); four patients were hypokalaemic on diuretic therapy (indapamidum); other 3 patients were hypokalaemic in the absence of diuretic therapy. Cushing's syndrome was diagnosed in 6 patients (7.5%): subclinical Cushing due to 4 cm right adrenal tumour - n = 1, overt ACTH-independent Cushing's syndrome due to: macronodular adrenal hyperplasia associated with primary hyperparathyroidism - n = 1; due to adrenal carcinoma - n = 1; due to adrenal adenomas - n = 2; Cushing's disease - n = 1). Pheochromocytomas were diagnosed in 3 patients (3.75%). Primary hyperaldosteronism was the most frequent cause of secondary

Endocrine-Disrupting Compounds in Aquatic Ecosystems.

EPA Science Inventory

Endocrine disrupting chemicals (EDCs) are a ubiquitous issue of concern in our aquatic systems. Commonly detected EDCs include natural and synthetic hormones, surfactants, plasticizers, disinfectants, herbicides and metals. The potency of these chemicals varies substantially, as ...

The interaction between ER and NFκB in resistance to endocrine therapy

PubMed Central

2012-01-01

Endocrine therapy is a commonly used treatment for estrogen receptor (ER)-positive breast cancer. Although endocrine therapy has a favorable outcome in many patients, development of resistance is common. Recent studies have shown that NFκB, a transcription factor regulating a wide variety of cellular processes, might play a role in the development of endocrine resistance. The precise interaction between ER and NFκB and how this contributes to the attenuated responsiveness of ER-positive breast cancer cells to hormonal treatment remains unclear. This review provides an overview of the mechanisms of action for both transcription factors and focuses on the current knowledge explaining how ER and NFκB affect each other's activity and how this cross-talk might contribute to the development of an endocrine resistance phenotype in breast cancer cells. PMID:22963717

Phytochemicals for taming agitated immune-endocrine-neural axis.

PubMed

Patel, Seema

2017-07-01

Homeostasis of immune-endocrine-neural axis is paramount for human health. If this axis gets agitated due to age, genetic variations, environmental exposures or lifestyle assaults, a cascade of adverse reactions occurs in human body. Cytokines, hormones and neurotransmitters, the effector molecules of this axis behave erratically, leading to a gamut of neural, endocrine, autoimmune, and metabolic diseases. Current panel of drugs can tackle some of them but not in a sustainable, benign way as a myriad of side effects, causal of them have been documented. In this context, phytochemicals, the secondary metabolites of plants seem beneficial. These bioactive constituents encompassing polyphenols, alkaloids, flavonoids, terpenoids, tannins, lignans, stilbenoids (resveratrol), saponins, polysaccharides, glycosides, and lectins etc. have been proven to exert antioxidant, anti-inflammatory, hypolipidemic, hypotensive, antidiabetic, anticancer, immunomodulatory, anti-allergic, analgesic, hepatoprotective, neuroprotective, dermatoprotective, and antimicrobial properties, among a litany of other biological effects. This review presents a holistic perspective of common afflictions resultant of immune-endocrine-neural axis disruption, and the phytochemicals capable of restoring their normalcy and mitigating the ailments. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

77 FR 12297 - Petition To Demonstrate Paperwork Reduction Act Compliance of the Endocrine Disruptor Screening...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-29

... Paperwork Reduction Act Compliance of the Endocrine Disruptor Screening Program; Notice of Availability... chemicals to receive orders under the Endocrine Disruptor Screening Program by demonstrating the information... potential endocrine effects. Potentially affected entities identified by the North American Industrial...

Human endometrial cell coculture reduces the endocrine disruptor toxicity on mouse embryo development

PubMed Central

2012-01-01

Backgrounds Previous studies suggested that endocrine disruptors (ED) are toxic on preimplantation embryos and inhibit development of embryos in vitro culture. However, information about the toxicity of endocrine disruptors on preimplantation development of embryo in human reproductive environment is lacking. Methods Bisphenol A (BPA) and Aroclor 1254 (polychlorinated biphenyls) were used as endocrine disruptors in this study. Mouse 2-cell embryos were cultured in medium alone or vehicle or co-cultured with human endometrial epithelial layers in increasing ED concentrations. Results At 72 hours the percentage of normal blastocyst were decreased by ED in a dose-dependent manner while the co-culture system significantly enhanced the rate and reduced the toxicity of endocrine disruptors on the embryonic development in vitro. Conclusions In conclusion, although EDs have the toxic effect on embryo development, the co-culture with human endometrial cell reduced the preimplantation embryo from it thereby making human reproductive environment protective to preimplantation embryo from the toxicity of endocrine disruptors. PMID:22546201

Initial experience with gamma knife surgery for endocrine ophthalmopathy.

PubMed

Antico, Julio C; Crovetto, Luis; Tenca, Eduardo; Artes, Carlos

2005-01-01

The aim of this study was to evaluate both the effectiveness and safety of the treatment of endocrine ophthalmopathy with gamma knife surgery (GKS). Five patients were included in a prospective study designed to assess the results of GKS of endocrine ophthalmopathy secondary to Graves disease. All the patients completed a 2-year follow-up period. During this period, the patients were evaluated both clinically and by means of additional methods, including computerized tomography and magnetic resonance imaging studies. The minimum dose delivered to the 50% isodose line was 6.5 Gy in all the patients. In all cases, a clinical improvement was observed. The best effect was seen in symptom regression related to soft-tissue involvement. No treatment-related side effects were detected. In light of the results obtained the authors consider that GKS may be a safe and effective way to treat endocrine ophthalmopathy.

Genetics of Endocrine and Neuroendocrine Neoplasias (PDQ®)—Health Professional Version

Cancer.gov

Endocrine and neuroendocrine neoplasias may be inherited in syndromes such as multiple endocrine neoplasia types 1 and 2 (MEN1 and MEN2), familial pheochromocytoma and paraganglioma, and Carney-Stratakis syndrome. Learn about the genetics, clinical manifestations, and management of these hereditary cancer syndromes in this expert-reviewed summary.

Endocrine system on chip for a diabetes treatment model.

PubMed

Nguyen, Dao Thi Thuy; van Noort, Danny; Jeong, In-Kyung; Park, Sungsu

2017-02-21

The endocrine system is a collection of glands producing hormones which, among others, regulates metabolism, growth and development. One important group of endocrine diseases is diabetes, which is caused by a deficiency or diminished effectiveness of endogenous insulin. By using a microfluidic perfused 3D cell-culture chip, we developed an 'endocrine system on chip' to potentially be able to screen drugs for the treatment of diabetes by measuring insulin release over time. Insulin-secreting β-cells are located in the pancreas, while L-cells, located in the small intestines, stimulate insulin secretion. Thus, we constructed a co-culture of intestinal-pancreatic cells to measure the effect of glucose on the production of glucagon-like peptide-1 (GLP-1) from the L-cell line (GLUTag) and insulin from the pancreatic β-cell line (INS-1). After three days of culture, both cell lines formed aggregates, exhibited 3D cell morphology, and showed good viability (>95%). We separately measured the dynamic profile of GLP-1 and insulin release at glucose concentrations of 0.5 and 20 mM, as well as the combined effect of GLP-1 on insulin production at these glucose concentrations. In response to glucose stimuli, GLUTag and INS-1 cells produced higher amounts of GLP-1 and insulin, respectively, compared to a static 2D cell culture. INS-1 combined with GLUTag cells exhibited an even higher insulin production in response to glucose stimulation. At higher glucose concentrations, the diabetes model on chip showed faster saturation of the insulin level. Our results suggest that the endocrine system developed in this study is a useful tool for observing dynamical changes in endocrine hormones (GLP-1 and insulin) in a glucose-dependent environment. Moreover, it can potentially be used to screen GLP-1 analogues and natural insulin and GLP-1 stimulants for diabetes treatment.

Endocrine Profiling and Prioritization of Environmental Chemicals Using ToxCast Data

PubMed Central

Reif, David M.; Martin, Matthew T.; Tan, Shirlee W.; Houck, Keith A.; Judson, Richard S.; Richard, Ann M.; Knudsen, Thomas B.; Dix, David J.; Kavlock, Robert J.

2010-01-01

Background The prioritization of chemicals for toxicity testing is a primary goal of the U.S. Environmental Protection Agency (EPA) ToxCast™ program. Phase I of ToxCast used a battery of 467 in vitro, high-throughput screening assays to assess 309 environmental chemicals. One important mode of action leading to toxicity is endocrine disruption, and the U.S. EPA’s Endocrine Disruptor Screening Program (EDSP) has been charged with screening pesticide chemicals and environmental contaminants for their potential to affect the endocrine systems of humans and wildlife. Objective The goal of this study was to develop a flexible method to facilitate the rational prioritization of chemicals for further evaluation and demonstrate its application as a candidate decision-support tool for EDSP. Methods Focusing on estrogen, androgen, and thyroid pathways, we defined putative endocrine profiles and derived a relative rank or score for the entire ToxCast library of 309 unique chemicals. Effects on other nuclear receptors and xenobiotic metabolizing enzymes were also considered, as were pertinent chemical descriptors and pathways relevant to endocrine-mediated signaling. Results Combining multiple data sources into an overall, weight-of-evidence Toxicological Priority Index (ToxPi) score for prioritizing further chemical testing resulted in more robust conclusions than any single data source taken alone. Conclusions Incorporating data from in vitro assays, chemical descriptors, and biological pathways in this prioritization schema provided a flexible, comprehensive visualization and ranking of each chemical’s potential endocrine activity. Importantly, ToxPi profiles provide a transparent visualization of the relative contribution of all information sources to an overall priority ranking. The method developed here is readily adaptable to diverse chemical prioritization tasks. PMID:20826373

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.

Causes of short stature in Pakistani children found at an Endocrine Center

PubMed Central

Jawa, Ali; Riaz, Syed Hunain; Khan Assir, Muhammad Zaman; Afreen, Bahjat; Riaz, Amna; Akram, Javed

2016-01-01

Background and Objective: Short stature is defined as height below 3rd centile. Causes of short stature can range from familial, endocrine disorders, chronic diseases to chromosomal disorders. Most common cause in literature being idiopathic short stature. Early detection and management of remedial disorders like malnutrition and vitamin D deficiency, Endocrine disorders like growth hormone deficiency & hypothyroidism can lead to attainment of expected height. Pakistani data shows idiopathic short stature as the most common cause of short stature. Our study aimed at detecting causes of short stature in children/adolescents at an Endocrine referral center. Methods: A retrospective study was conducted at WILCARE Center for Diabetes, Endocrinology & Metabolism, Lahore on 70 well-nourished children/adolescents. The patients had been evaluated clinically, biochemically and radiologically as needed. Biochemical testing included hormonal testing as well to detect endocrine causes. Data was entered and analyzed in SPSS 20.0. Results: Leading cause of short stature in our population was Growth Hormone (GH) deficiency seen in 48 out of 70 (69%) patients. Second most common endocrine abnormality seen in these patients was Vitamin D deficiency [44 out of 70 patients (63%)]. Primary hypothyroidism; pan-hypopituitarism & adrenal insufficiency were other endocrine causes. The weight for age was below 3rd percentile in 57 (81%) patients, with no association with other major causes. Conclusion: Growth hormone and Vitamin D deficiency constitute one of the major causes of short stature among well-nourished children with short stature in Pakistan. PMID:28083018

The Role of ARX in Human Pancreatic Endocrine Specification

PubMed Central

Gage, Blair K.; Asadi, Ali; Baker, Robert K.; Webber, Travis D.; Wang, Rennian; Itoh, Masayuki; Hayashi, Masaharu; Miyata, Rie; Akashi, Takumi; Kieffer, Timothy J.

2015-01-01

The in vitro differentiation of human embryonic stem cells (hESCs) offers a model system to explore human development. Humans with mutations in the transcription factor Aristaless Related Homeobox (ARX) often suffer from the syndrome X-linked lissencephaly with ambiguous genitalia (XLAG), affecting many cell types including those of the pancreas. Indeed, XLAG pancreatic islets lack glucagon and pancreatic polypeptide-positive cells but retain somatostatin, insulin, and ghrelin-positive cells. To further examine the role of ARX in human pancreatic endocrine development, we utilized genomic editing in hESCs to generate deletions in ARX. ARX knockout hESCs retained pancreatic differentiation capacity and ARX knockout endocrine cells were biased toward somatostatin-positive cells (94% of endocrine cells) with reduced pancreatic polypeptide (rarely detected), glucagon (90% reduced) and insulin-positive (65% reduced) lineages. ARX knockout somatostatin-positive cells shared expression patterns with human fetal and adult δ-cells. Differentiated ARX knockout cells upregulated PAX4, NKX2.2, ISL1, HHEX, PCSK1, PCSK2 expression while downregulating PAX6 and IRX2. Re-expression of ARX in ARX knockout pancreatic progenitors reduced HHEX and increased PAX6 and insulin expression following differentiation. Taken together these data suggest that ARX plays a key role in pancreatic endocrine fate specification of pancreatic polypeptide, somatostatin, glucagon and insulin positive cells from hESCs. PMID:26633894

The Role of ARX in Human Pancreatic Endocrine Specification.

PubMed

Gage, Blair K; Asadi, Ali; Baker, Robert K; Webber, Travis D; Wang, Rennian; Itoh, Masayuki; Hayashi, Masaharu; Miyata, Rie; Akashi, Takumi; Kieffer, Timothy J

2015-01-01

The in vitro differentiation of human embryonic stem cells (hESCs) offers a model system to explore human development. Humans with mutations in the transcription factor Aristaless Related Homeobox (ARX) often suffer from the syndrome X-linked lissencephaly with ambiguous genitalia (XLAG), affecting many cell types including those of the pancreas. Indeed, XLAG pancreatic islets lack glucagon and pancreatic polypeptide-positive cells but retain somatostatin, insulin, and ghrelin-positive cells. To further examine the role of ARX in human pancreatic endocrine development, we utilized genomic editing in hESCs to generate deletions in ARX. ARX knockout hESCs retained pancreatic differentiation capacity and ARX knockout endocrine cells were biased toward somatostatin-positive cells (94% of endocrine cells) with reduced pancreatic polypeptide (rarely detected), glucagon (90% reduced) and insulin-positive (65% reduced) lineages. ARX knockout somatostatin-positive cells shared expression patterns with human fetal and adult δ-cells. Differentiated ARX knockout cells upregulated PAX4, NKX2.2, ISL1, HHEX, PCSK1, PCSK2 expression while downregulating PAX6 and IRX2. Re-expression of ARX in ARX knockout pancreatic progenitors reduced HHEX and increased PAX6 and insulin expression following differentiation. Taken together these data suggest that ARX plays a key role in pancreatic endocrine fate specification of pancreatic polypeptide, somatostatin, glucagon and insulin positive cells from hESCs.

Phase 1b Food Based Modulation of Biomarkers in Human Tissues at High-Risk for Oral Cancer.

ClinicalTrials.gov

2018-03-05

Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Salivary Gland Squamous Cell Carcinoma; Stage 0 Hypopharyngeal Cancer; Stage 0 Laryngeal Cancer; Stage 0 Lip and Oral Cavity Cancer; Stage 0 Nasopharyngeal Cancer; Stage 0 Oropharyngeal Cancer; Stage 0 Paranasal Sinus and Nasal Cavity Cancer; Stage I Salivary Gland Cancer; Stage I Squamous Cell Carcinoma of the Hypopharynx; Stage I Squamous Cell Carcinoma of the Larynx; Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage I Squamous Cell Carcinoma of the Nasopharynx; Stage I Squamous Cell Carcinoma of the Oropharynx; Stage I Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage I Verrucous Carcinoma of the Larynx; Stage I Verrucous Carcinoma of the Oral Cavity; Stage II Salivary Gland Cancer; Stage II Squamous Cell Carcinoma of the Hypopharynx; Stage II Squamous Cell Carcinoma of the Larynx; Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage II Squamous Cell Carcinoma of the Nasopharynx; Stage II Squamous Cell Carcinoma of the Oropharynx; Stage II Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage II Verrucous Carcinoma of the Larynx; Stage II Verrucous Carcinoma of the Oral Cavity; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Nasal Cavity and Paranasal Sinus Cancer; Stage IVA

An epistemological inquiry into the endocrine disruptor thesis.

PubMed

Krimsky, S

2001-12-01

For about a decade the term endocrine disruptor has become synonymous with a new research initiative that has been investigating the effects of hormonally active xenobiotics on biological systems. The scientific thesis behind the new research initiative is discussed and it is argued that there is a need for more emphasis on theory development and conceptual clarification that will give coherence to a field experiencing a rapid growth of empirical studies. Reflections on scientific methodology in this field will also help clarify whether endocrine disruptors symbolize a new etiology of chemically induced disease or represent variations of traditional chemical toxicology.

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...

Switched impulsive control of the endocrine disruptor diethylstilbestrol singular model

NASA Astrophysics Data System (ADS)

Zamani, Iman; Shafiee, Masoud; Ibeas, Asier; de la Sen, M.

2014-12-01

In this work, a switched and impulsive controller is designed to control the Endocrine Disruptor Diethylstilbestrol mechanism which is usually modeled as a singular system. Then the exponential stabilization property of the proposed switched and impulsive singular model is discussed under matrix inequalities. A design algorithm is given and applied for the physiological process of endocrine disruptor diethylstilbestrol model to illustrate the effectiveness of the results.

Is adjuvant chemotherapy of benefit for postmenopausal women who receive endocrine treatment for highly endocrine-responsive, node-positive breast cancer? International Breast Cancer Study Group Trials VII and 12-93.

PubMed

Pagani, Olivia; Gelber, Shari; Simoncini, Edda; Castiglione-Gertsch, Monica; Price, Karen N; Gelber, Richard D; Holmberg, Stig B; Crivellari, Diana; Collins, John; Lindtner, Jurij; Thürlimann, Beat; Fey, Martin F; Murray, Elizabeth; Forbes, John F; Coates, Alan S; Goldhirsch, Aron

2009-08-01

To compare the efficacy of chemoendocrine treatment with that of endocrine treatment (ET) alone for postmenopausal women with highly endocrine responsive breast cancer. In the International Breast Cancer Study Group (IBCSG) Trials VII and 12-93, postmenopausal women with node-positive, estrogen receptor (ER)-positive or ER-negative, operable breast cancer were randomized to receive either chemotherapy or endocrine therapy or combined chemoendocrine treatment. Results were analyzed overall in the cohort of 893 patients with endocrine-responsive disease, and according to prospectively defined categories of ER, age and nodal status. STEPP analyses assessed chemotherapy effect. The median follow-up was 13 years. Adding chemotherapy reduced the relative risk of a disease-free survival event by 19% (P = 0.02) compared with ET alone. STEPP analyses showed little effect of chemotherapy for tumors with high levels of ER expression (P = 0.07), or for the cohort with one positive node (P = 0.03). Chemotherapy significantly improves disease-free survival for postmenopausal women with endocrine-responsive breast cancer, but the magnitude of the effect is substantially attenuated if ER levels are high.

[Diabetes mellitus secondary to an endocrine pathology : when to think about it ?

PubMed

Rouiller, Nathalie; Jornayvaz, François R

2017-05-31

An endocrine disease can be associated with glucose intolerance or diabetes mellitus, and the latter can falsely be considered as type 2 diabetes. Glycemic imbalance can be a direct or indirect consequence of excessive hormone production. Endocrine diseases such as acromegaly, Cushing's syndrome and pheochromocytoma can increase glucose production and cause insulin resistance. Hyperthyroidism, hyperaldosteronism, glucagonoma and somatostatinoma lead to hyperglycemia by other physiopathological mechanisms detailed in this article. When a clinical picture suggests an endocrine disease, several analyses need to be done in order to avoid treatment escalation of diabetes.

Characterization of potential endocrine-related health effects at low-dose levels of exposure to PCBs.

PubMed Central

Brouwer, A; Longnecker, M P; Birnbaum, L S; Cogliano, J; Kostyniak, P; Moore, J; Schantz, S; Winneke, G

1999-01-01

This article addresses issues related to the characterization of endocrine-related health effects resulting from low-level exposures to polychlorinated biphenyls (PCBs). It is not intended to be a comprehensive review of the literature but reflects workshop discussions. "The Characterizing the Effects of Endocrine Disruptors on Human Health at Environmental Exposure Levels," workshop provided a forum to discuss the methods and data needed to improve risk assessments of endocrine disruptors. This article contains an overview of endocrine-related (estrogen and thyroid system) interactions and other low-dose effects of PCBs. The data set on endocrine effects includes results obtained from mechanistic methods/ and models (receptor based, metabolism based, and transport protein based), as well as from (italic)in vivo(/italic) models, including studies with experimental animals and wildlife species. Other low-dose effects induced by PCBs, such as neurodevelopmental and reproductive effects and endocrine-sensitive tumors, have been evaluated with respect to a possible causative linkage with PCB-induced alterations in endocrine systems. In addition, studies of low-dose exposure and effects in human populations are presented and critically evaluated. A list of conclusions and recommendations is included. PMID:10421775

Central control of glucose homeostasis: the brain--endocrine pancreas axis.

PubMed

Thorens, B

2010-10-01

A large body of data gathered over the last decades has delineated the neuronal pathways that link the central nervous system with the autonomic innervation of the endocrine pancreas, which controls alpha- and beta-cell secretion activity and mass. These are important regulatory functions that are certainly keys for preserving the capacity of the endocrine pancreas to control glucose homeostasis over a lifetime. Identifying the cells involved in controlling the autonomic innervation of the endocrine pancreas, in response to nutrient, hormonal and environmental cues and how these cues are detected to activate neuronal activity are important goals of current research. Elucidation of these questions may possibly lead to new means for preserving or restoring defects in insulin and glucagon secretion associated with type 2 diabetes. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Endocrine disruptor induction of epigenetic transgenerational inheritance of disease.

PubMed

Skinner, Michael K

2014-12-01

Environmental exposures such as toxicants, nutrition and stress have been shown to promote the epigenetic transgenerational inheritance of disease susceptibility. Endocrine disruptors are one of the largest groups of specific toxicants shown to promote this form of epigenetic inheritance. These environmental compounds that interfere with normal endocrine signaling are one of the largest classes of toxicants we are exposed to on a daily level. The ability of ancestral exposures to promote disease susceptibility significantly increases the potential biohazards of these toxicants. Therefore, what your great-grandmother was exposed to during pregnancy may influence your disease development, even in the absence of any exposure, and you are going to pass this on to your grandchildren. This non-genetic form of inheritance significantly impacts our understanding of biology from the origins of disease to evolutionary biology. The current review will describe the previous studies and endocrine disruptors shown to promote the epigenetic transgenerational inheritance of disease. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Endocrine Disruptor Induction of Epigenetic Transgenerational Inheritance of Disease

PubMed Central

Skinner, Michael K.

2014-01-01

Environmental exposures such as toxicants, nutrition and stress have been shown to promote the epigenetic transgenerational inheritance of disease susceptibility. Endocrine disruptors are one of the largest groups of specific toxicants shown to promote this form of epigenetic inheritance. These environmental compounds that interfere with normal endocrine signaling are one of the largest classes of toxicants we are exposed to on a daily level. The ability of ancestral exposures to promote disease susceptibility significantly increases the potential biohazards of these toxicants. Therefore, what your great-grandmother was exposed to during pregnancy may influence your disease development, even in the absence of any exposure, and you are going to pass this on to your grandchildren. This non-genetic form of inheritance significantly impacts our understanding of biology from the origins of disease to evolutionary biology. The current review will describe the previous studies and endocrine disruptors shown to promote the epigenetic transgenerational inheritance of disease. PMID:25088466

Video-assisted endocrine neck surgery: state of the art.

PubMed

Sessa, Luca; Lombardi, Celestino Pio; De Crea, Carmela; Raffaelli, Marco; Bellantone, Rocco

2017-06-01

During the last two decades, several minimally invasive approaches for endocrine neck surgery have been developed. Minimally invasive video-assisted approaches (minimally invasive video-assisted parathyroidectomy and minimally invasive video-assisted thyroidectomy) gained a quite large worldwide diffusion, maybe because these techniques combine the advantages related to the endoscopic magnification with those due to the close similarity with the conventional surgery that makes these surgical approaches reproducible and feasible in different surgical settings. Several comparative studies have demonstrated the advantages of minimally invasive video-assisted neck surgery in terms of reduced postoperative pain, better cosmetic result, and higher patients' satisfaction over the conventional endocrine neck surgery. An accurate patients' selection plays a key role to ensure the success of minimally invasive video-assisted approaches. To date, in selected cases and in experienced Center, minimally invasive video-assisted endocrine neck surgery could be considered the standard treatment or at least a safe and effective surgical option.

ORD RESEARCH PLAN FOR ENDOCRINE DISRUPTORS

EPA Science Inventory

This research strategy was developed to provide a roadmap for the EPA Office of Research and Development's program on endocrine disruptors. It was developed by a team of scientists representing all of ORD's National Laboratories and Centers and is intended to pro...

CONTAMINANT-ASSOCIATED ENDOCRINE DISRUPTION IN REPTILES.

EPA Science Inventory

The data presented suggest that contaminants can alter the endocrine and reproductive system of reptiles by mimicking hormones and by various mechanisms other than direct hormonal mimicry. However, these data indicate, as do many other studies using various vertebrates, that a fo...

Investigation of the feasibility of elective irradiation to neck level Ib using intensity-modulated radiotherapy for patients with nasopharyngeal carcinoma: a retrospective analysis.

PubMed

Zhang, Fan; Cheng, Yi-Kan; Li, Wen-Fei; Guo, Rui; Chen, Lei; Sun, Ying; Mao, Yan-Ping; Zhou, Guan-Qun; Liu, Xu; Liu, Li-Zhi; Lin, Ai-Hua; Tang, Ling-Long; Ma, Jun

2015-10-15

To assess the feasibility of elective neck irradiation to level Ib in nasopharyngeal carcinoma (NPC) using intensity-modulated radiation therapy (IMRT). We retrospectively analyzed 1438 patients with newly-diagnosed, non-metastatic and biopsy-proven NPC treated with IMRT. Greatest dimension of level IIa LNs (DLN-IIa) ≥ 20 mm and/or level IIa LNs with extracapsular spread (ES), oropharynx involvement and positive bilateral cervical lymph nodes (CLNs) were independently significantly associated with metastasis to level Ib LN at diagnosis. No recurrence at level Ib was observed in the 904 patients without these characteristics (median follow-up, 38.7 months; range, 1.3-57.8 months), these patients were classified as low risk. Level Ib irradiation was not an independent risk factor for locoregional failure-free survival, distant failure-free survival, failure-free survival or overall survival in low risk patients. The frequency of grade ≥ 2 subjective xerostomia at 12 months after radiotherapy was not significantly different between low risk patients who received level Ib-sparing, unilateral level Ib-covering or bilateral level Ib-covering IMRT. Level Ib-sparing IMRT should be safe and feasible for patients without a DLN-IIa ≥ 20 mm and/or level IIa LNs with ES, positive bilateral CLNs or oropharynx involvement at diagnosis. Further investigations based on specific criteria for dose constraints for the submandibular glands are warranted to confirm the benefit of elective level Ib irradiation.

Endocrine disruptors and prostate cancer risk

PubMed Central

Prins, Gail S

2010-01-01

There is increasing evidence both from epidemiology studies and animal models that specific endocrine-disrupting compounds may influence the development or progression of prostate cancer. In large part, these effects appear to be linked to interference with estrogen signaling, either through interacting with ERs or by influencing steroid metabolism and altering estrogen levels within the body. In humans, epidemiologic evidence links specific pesticides, PCBs and inorganic arsenic exposures to elevated prostate cancer risk. Studies in animal models also show augmentation of prostate carcinogenesis with several other environmental estrogenic compounds including cadmium, UV filters and BPA. Importantly, there appears to be heightened sensitivity of the prostate to these endocrine disruptors during the critical developmental windows including in utero and neonatal time points as well as during puberty. Thus infants and children may be considered a highly susceptible population for ED exposures and increased risk of prostate cancers with aging. PMID:18524946

Endocrine profiles and neuropsychologic correlates of functional hypothalamic amenorrhea in adolescents.

PubMed

Bomba, Monica; Gambera, Alessandro; Bonini, Luisa; Peroni, Maria; Neri, Francesca; Scagliola, Pasquale; Nacinovich, Renata

2007-04-01

To determine trigger factors and neuropsychologic correlates of functional hypothalamic amenorrhea (FHA) in adolescence and to evaluate the correlations with the endocrine-metabolic profile. Cross-sectional comparison of adolescents with FHA and eumenorrheic controls Academic medical institution Twenty adolescent girls with FHA (aged <18 years) and 20 normal cycling girls All subjects underwent endocrine-gynecologic (hormone) and neuropsychiatric (tests and interview) investigations. A separate semistructured interview was also used to investigate parents. Gonadotropins, leptin, prolactin, androgens, estrogens, cortisol, carrier proteins (SHBG, insulin-like growth factor-binding protein 1), and metabolic parameters (insulin, insulin-like growth factor 1, thyroid hormones) were assayed in FHA and control subjects. All girls were evaluated using a test for depression, a test for disordered eating, and a psychodynamic semistructured interview. Adolescents with FHA showed a particular susceptibility to common life events, restrictive disordered eating, depressive traits, and psychosomatic disorders. The endocrine-metabolic profile was strictly correlated to the severity of the psychopathology. Functional hypothalamic amenorrhea in adolescence is due to a particular neuropsychologic vulnerability to stress, probably related to familial relationship styles, expressed by a proportional endocrine impairment.

Society for Endocrinology Competency Framework for Adult Endocrine Nursing: 2nd edition.

PubMed

Kieffer, Veronica; Davies, Kate; Gibson, Christine; Middleton, Morag; Munday, Jean; Shalet, Shashana; Shepherd, Lisa; Yeoh, Phillip

2015-03-01

This competency framework was developed by a working group of endocrine specialist nurses with the support of the Society for Endocrinology to enhance the clinical care that adults with an endocrine disorder receive. Nurses should be able to demonstrate that they are functioning at an optimal level in order for patients to receive appropriate care. By formulating a competency framework from which an adult endocrine nurse specialist can work, it is envisaged that their development as professional practitioners can be enhanced. This is the second edition of the Competency Framework for Adult Endocrine Nursing. It introduces four new competencies on benign adrenal tumours, hypo- and hyperparathyroidism, osteoporosis and polycystic ovary syndrome. The authors and the Society for Endocrinology welcome constructive feedback on the document, both nationally and internationally, in anticipation that further developments and ideas can be incorporated into future versions. © 2015 Society for Endocrinology.

Screening for Secondary Endocrine Hypertension in Young Patients

PubMed Central

TRIFANESCU, Raluca; CARSOTE, Mara; CARAGHEORGHEOPOL, Andra; HORTOPAN, Dan; DUMITRASCU, Anda; DOBRESCU, Mariana; POIANA, Catalina

2013-01-01

ABSTRACT Background: Secondary endocrine hypertension accounts for 5-12% of hypertension's causes. In selected patients (type 2 diabetes mellitus, sleep apnea syndrome with resistant hypertension, sudden deterioration in hypertension control), prevalence could be higher. Objectives: To present etiology of endocrine secondary hypertension in a series of patients younger than 40 years at hypertension's onset. Material and methods: Medical records of 80 patients (39M/41F), aged 30.1 ± 8.2 years (range: 12-40 years), with maximum systolic blood pressure=190.4 ± 29.2 mm Hg, range: 145-300 mm Hg, maximum diastolic blood pressure=107.7 ± 16.9 mm Hg, range: 80-170 mm Hg) referred by cardiologists for endocrine hypertension screening were retrospectively reviewed. Cardiac and renal causes of secondary hypertension were previously excluded. In all patients, plasma catecholamines were measured by ELISA and plasma cortisol by immunochemiluminescence. Orthostatic aldosterone (ELISA) and direct renin (chemiluminescence) were measured in 48 patients. Results: Secondary endocrine hypertension was confirmed in 16 out of 80 patients (20%). Primary hyperaldosteronism was diagnosed in 7 (4M/3F) out of 48 screened patients (14.6%). i.e. 8.75% from whole group: 5 patients with adrenal tumors (3 left/2 right), 2 patients with bilateral adrenal hyperplasia; all patients were hypokalemic at diagnostic (average nadir K+ levels = 2.5 ± 0.5 mmol/L); four patients were hypokalaemic on diuretic therapy (indapamidum); other 3 patients were hypokalaemic in the absence of diuretic therapy. Cushing's syndrome was diagnosed in 6 patients (7.5%): subclinical Cushing due to 4 cm right adrenal tumour – n = 1, overt ACTH-independent Cushing's syndrome due to: macronodular adrenal hyperplasia associated with primary hyperparathyroidism – n = 1; due to adrenal carcinoma – n = 1; due to adrenal adenomas – n = 2; Cushing's disease – n = 1). Pheochromocytomas were diagnosed in 3 patients (3

RESEARCH PLAN FOR ENDOCRINE DISRUPTORS (DRAFT)

EPA Science Inventory

This research strategy was developed to provide a roadmap for the EPA Office of Research and Developments program on endocrine disruptors. It was developed by a team of scientists representing all of ORDs National Laboratories and Centers and is intended to provide guidance to bo...

Endocrine cells in ectocervical epithelium. An immunohistochemical and ultrastructural analysis.

PubMed

Fetissof, F; Arbeille, B; Boivin, F; Sam-Giao, M; Henrion, C; Lansac, J

1987-01-01

A systematic study of endocrine cells in the ectocervix was carried out using histochemical, immunohistochemical and ultrastructural techniques. Serotonin and calcitonin immunoreactive cells were demonstrated in this site. Serotonin and calcitonin immunoreactivities were coexpressed in the same endocrine cell. These distinctive cells were encountered in two main morphological varieties of ectocervical epithelium. Normal-appearing stratified squamous epithelium contained only very rare serotonin and calcitonin cells. In contrast, endocrine cells were fairly abundant in a specific epithelium termed "transitional-like". This type of epithelium was not only confined to the transformation zone but could also extend onto the portio as far as the vaginal cut margin. In some cases, transitional-like epithelium bore morphological resemblance to urothelium. In other cases, it could be regarded as basal cell hyperplasia or immature squamous metaplasia. Of interest, serotonin and calcitonin cells have been well-documented as normal inhabitants of some other non-squamous epithelia, such as urothelium or pseudostratified columnar epithelium. Therefore, it is suggested that certain ectocervical epithelia show some similarities to urothelium, in respect of their morphological appearance and endocrine profile. Further investigations using more objective and specific markers of urothelial cells are needed to assess the exact degree of homology connecting all these types of epithelium.

The role of retinoic acid receptors and their cognate ligands in reproduction in a context of triorganotin based endocrine disrupting chemicals.

PubMed

Macejova, Dana; Toporova, L; Brtko, J

2016-07-01

Retinoic acid (RA), an active form of vitamin A, regulates the embryonic development, male and female reproduction and induces important effects on the cell development, proliferation, and differentiation. These effects are mediated by the retinoid (RAR) and rexinoid nuclear receptors (RXR), which are considered to be a ligand-activated, DNA-binding, trans-acting, and transcription-modulating proteins, involved in a general molecular mechanism responsible for the transcriptional responses in target genes. Organotin compounds are typical environmental contaminants and suspected endocrine disrupting substances. They may affect processes of reproductive system in mammals, predominantly via nuclear receptor signaling pathways. Triorganotins, such as tributyltin chloride (TBTCl) and triphenyltin chloride (TPTCl), are capable to bind to RXR molecules, and thus represent potent agonists of RXR subtypes of nuclear receptors not sharing any structural characteristics with endogenous ligands of nuclear receptors. Th is article summarizes selected effects of biologically active retinoids and rexinoids on both male and female reproduction and also deals with the effects of organotin compounds evoking endocrine disrupting actions in reproduction.

75 FR 77869 - Endocrine Disruptor Screening Program; Second List of Chemicals for Tier 1 Screening; Extension...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-14

... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OPPT-2009-0477; FRL-8856-5] Endocrine Disruptor Screening... Federal Register issue of November 17, 2010, concerning the Endocrine Disruptor Screening Program's (EDSP... CONTACT. List of Subjects Environmental protection, Chemicals, Drinking water, Endocrine disruptors...

High efficiency endocrine operation protocol: From design to implementation.

PubMed

Mascarella, Marco A; Lahrichi, Nadia; Cloutier, Fabienne; Kleiman, Simcha; Payne, Richard J; Rosenberg, Lawrence

2016-10-01

We developed a high efficiency endocrine operative protocol based on a mathematical programming approach, process reengineering, and value-stream mapping to increase the number of operations completed per day without increasing operating room time at a tertiary-care, academic center. Using this protocol, a case-control study of 72 patients undergoing endocrine operation during high efficiency days were age, sex, and procedure-matched to 72 patients undergoing operation during standard days. The demographic profile, operative times, and perioperative complications were noted. The average number of cases per 8-hour workday in the high efficiency and standard operating rooms were 7 and 5, respectively. Mean procedure times in both groups were similar. The turnaround time (mean ± standard deviation) in the high efficiency group was 8.5 (±2.7) minutes as compared with 15.4 (±4.9) minutes in the standard group (P < .001). Transient postoperative hypocalcemia was 6.9% (5/72) and 8.3% (6/72) for the high efficiency and standard groups, respectively (P = .99). In this study, patients undergoing high efficiency endocrine operation had similar procedure times and perioperative complications compared with the standard group. The proposed high efficiency protocol seems to better utilize operative time and decrease the backlog of patients waiting for endocrine operation in a country with a universal national health care program. Copyright © 2016 Elsevier Inc. All rights reserved.

The eye as a window to rare endocrine disorders

PubMed Central

Chopra, Rupali; Chander, Ashish; Jacob, Jubbin J.

2012-01-01

The human eye, as an organ, can offer critical clues to the diagnosis of various systemic illnesses. Ocular changes are common in various endocrine disorders such as diabetes mellitus and Graves’ disease. However there exist a large number of lesser known endocrine disorders where ocular involvement is significant. Awareness of these associations is the first step in the diagnosis and management of these complex patients. The rare syndromes involving the pituitary hypothalamic axis with significant ocular involvement include Septo-optic dysplasia, Kallman's syndrome, and Empty Sella syndrome all affecting the optic nerve at the optic chiasa. The syndromes involving the thyroid and parathyroid glands that have ocular manifestations and are rare include Mc Cune Albright syndrome wherein optic nerve decompression may occur due to fibrous dysplasia, primary hyperparathyroidism that may present as red eye due to scleritis and Ascher syndrome wherein ptosis occurs. Allgrove's syndrome, Cushing's disease, and Addison's disease are the rare endocrine syndromes discussed involving the adrenals and eye. Ocular involvement is also seen in gonadal syndromes such as Bardet Biedl, Turner's, Rothmund's, and Klinefelter's syndrome. This review also highlights the ocular manifestation of miscellaneous syndromes such as Werner's, Cockayne's, Wolfram's, Kearns Sayre's, and Autoimmune polyendocrine syndrome. The knowledge of these relatively uncommon endocrine disorders and their ocular manifestations will help an endocrinologist reach a diagnosis and will alert an ophthalmologist to seek specialty consultation of an endocrinologist when encountered with such cases. PMID:22629495

Barriers to and facilitative processes of endocrine therapy adherence among women with breast cancer.

PubMed

Bright, Emma E; Petrie, Keith J; Partridge, Ann H; Stanton, Annette L

2016-07-01

The treatment of chronic illness, and the prevention of disease progression and recurrence, often involve long-term adherence to prescription medications in breast cancer. Despite the survival benefit of endocrine therapies, nonadherence remains high. In this study, we examined barriers to and facilitators of endocrine therapy adherence among women with breast cancer (n = 1371). Participants currently taking tamoxifen or aromatase inhibitors were recruited from Dr. Susan Love Research Foundation's Army of Women(®) Registry. Participants responded online to open-ended and close-ended questions about thoughts, feelings, and behaviors relevant to endocrine therapy. Two weeks later, women were invited to complete a second online questionnaire regarding current endocrine therapy adherence. Approximately one-third (36 %) of participants reported the presence of factors that make endocrine therapy difficult; reporting any barrier to medication adherence was significantly associated with nonadherence (P < 0.001). In addition, 31 % of women used one or more strategies to maintain their motivation to adhere and the use of cognitive self-talk (e.g., thoughts regarding endocrine therapy efficacy) was related to higher adherence. Hierarchical linear regressions revealed a significant behavioral barrier × behavioral facilitator interaction (P < 0.05); participants who endorsed a behavioral barrier in the absence of a behavioral facilitator reported the lowest adherence. Findings suggest that a sizeable minority of women face barriers to taking endocrine therapy, which are associated with nonadherence.

76 FR 49473 - Petition to Maximize Practical Utility of List 1 Chemicals Screened Through EPA's Endocrine...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-10

... Utility of List 1 Chemicals Screened Through EPA's Endocrine Disruptor Screening Program; Notice of... to the test orders issued under the Endocrine Disruptor Screening Program. DATES: Comments must be... testing of chemical substances for potential endocrine effects. Potentially affected entities, identified...

Endocrine and Metabolic Adverse Effects of Psychotropic Medications in Children and Adolescents

ERIC Educational Resources Information Center

Correll, Christoph U.; Carlson, Harold E.

2006-01-01

Objective: Despite increasing use of psychotropic medications in children and adolescents, data regarding their efficacy and safety are limited. Endocrine and metabolic adverse effects are among the most concerning adverse effects of commonly used psychotropic medications. Method: Selective review of endocrine and metabolic effects of psychotropic…

[Immunization and bacterial pathogens in the oropharynx as risk factors for alopecia areata].

PubMed

Morales-Sánchez, M A; Domínguez-Gómez, M A; Jurado-Santa Cruz, F; Peralta-Pedrero, M L

2010-06-01

Alopecia areata is an autoimmune inflammatory disease affecting the hair follicles. Researchers are currently interested in whether the presence of bacterial pathogens and/or a history of immunization can trigger an autoimmune response in patients who are genetically predisposed. This study aimed to determine whether there is an association between the development of alopecia areata and throat carriage of bacterial pathogens or a history of immunization. Sixty-five men and women with alopecia areata and 65 control patients with other skin diseases were studied at the Dr Ladislao de la Pascua Dermatology Clinic between September 2008 and February 2009. The patients ranged in age from 18-59 years. Patients with scalp diseases were excluded from the control group. In all cases, the patient was questioned about immunizations received in the previous 6 months, and a throat swab was cultured. A history of immunization (odds ratio [OR], 3.3; 95% confidence interval [CI], 1.6-6.7; P=.001), the presence of bacterial pathogens in the oropharynx (OR, 2.6; 95% CI, 1.1-6.2; P=.033), and being a carrier of Streptococcus pyogenes (OR, 2.1; 95% CI, 1.7-2.5; P=.042) were risk factors for alopecia areata. Klebsiella pneumoniae, S. pyogenes, Pseudomonas aeruginosa, Streptococcus pneumoniae, Serratia marcescens and Escherichia coli were isolated from cultures. This is the first study to show an association between alopecia areata and throat carriage of bacterial pathogens or history of immunization, as risk factors for development of the disease. Given the characteristics of our study population, the association appears valid for patients with less than 25% hair loss and a course of disease under 1 year.

The scaffold protein RACK1 is a target of endocrine disrupting chemicals (EDCs) with important implication in immunity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buoso, Erica; Galasso, Marilisa; Ronfani, Melania

We recently demonstrated the existence of a complex hormonal balance between steroid hormones in the control of RACK1 (Receptor for Activated C Kinase 1) expression and immune activation, suggesting that this scaffold protein may also be targeted by endocrine disrupting chemicals (EDCs). As a proof of concept, we investigated the effect of the doping agent nandrolone, an androgen receptor (AR) agonist, and of p,p′DDT (dichlorodiphenyltrichloroethane) and its main metabolite p,p′DDE (dichlorodiphenyldichloroethylene), a weak and strong AR antagonist, respectively, on RACK1 expression and innate immune response. In analogy to endogenous androgens, nandrolone induced a dose-related increase in RACK1 transcriptional activity andmore » protein expression, resulting in increased LPS-induced IL-8 and TNF-α production and proliferation in THP-1 cells. Conversely, p,p′DDT and p,p′DDE significantly decrease RACK1 expression, LPS-induced cytokine production and CD86 expression; with p,p′DDE exerting a stronger repressor effect than p,p′DDT, consistent with its stronger AR antagonistic effect. These results indicate that RACK1 could be a relevant target of EDCs, responding in opposite ways to agonist or antagonist of AR, representing a bridge between the endocrine system and the innate immune system. - Highlights: • RACK1 expression can be induced by AR agonists with a consequent enhancement of the response to LPS. • RACK1 can be negatively modulated by the AR antagonists DDT and its main metabolite p,p′DDE. • RACK1 can be a relevant target of EDCs, representing a bridge between the endocrine system and the immune system.« less

Psycho-Neuro-Endocrine-Immunology: A Psychobiological Concept.

PubMed

França, Katlein; Lotti, Torello M

2017-01-01

Psycho-Neuro-Endocrine-Immunology (P.N.E.I.) is a scientific field of study that investigates the link between bidirectional communications among the nervous system, the endocrine system, and the immune system and the correlations of this cross-talk with physical health. The P.N.E.I. innovative medical approach represents a paradigm shift from a strictly biomedical view of health and disease taken as hermetically sealed compartments to a more interdisciplinary one. The key element of P.N.E.I. approach is represented by the concept of bidirectional cross-talk between the psychoneuroendocrine and immune systems. The Low Dose Medicine is one of the most promising approaches able to allow the researchers to design innovative therapeutic strategies for the treatment of skin diseases based on the rebalance of the immune response.

[Endocrine orbitopathy - the topic still alive].

PubMed

Fryšák, Zdeněk; Karásek, David; Halenka, Milan

Endocrine orbitopathy (EO) must be understood mainly as a result of oxidative stress. The pathological process finally affects both the appearance and vision of the patient. In the case of inappropriate or late treatment or lack of patient cooperation, it significantly influences the quality of life of those affected. In spite of the sophisticated dia-gnostic algorithms, in some cases it is difficult to confirm the diagnosis of EO. The range of laboratory methods, the essential part of the diagnostic process, has only recently been extended by the possibility of quantification of specific, stimulating immunoglobulins (TSI). A major shortcoming may be seen in an undervalued importance of orbital ultrasonography, in particular of the eye muscles (US).Key words: biological treatment - endocrine orbitopathy (EO) - Graves-Basedow disease (GB) - "hashitoxicosis" (HTX) - hyaluronan synthase 2 (HAS2) - thyroid-blocking immunoglobulins (TBI) - thyroid-stimulating immunoglobulins (TSI) - hyaluronic acid (HA) - lymphocytary, Hashimotos thyroiditis (HT) - pulse therapy - TSH-receptor - transcription factors FOXOs - orbital ultrasonography, mainly of the eye muscles (US).

Endocrine cells in the denervated intestine

PubMed Central

Santos, Gilda C; Zucoloto, Sérgio; Garcia, Sérgio B

2000-01-01

This study deals with the effects of myenteric denervation of the proximal jejunum on endocrine cell population of the crypt-villus unit, 5 months after treatment with benzalkonium chloride (BAC). Male Wistar albino rats weighing on average 100 g were allocated to two groups: the BAC group − the proximal jejunal serosa was treated with 2 mm BAC for 30 min, and the control group − treated with saline solution (0,9% NaCl). There was a significant reduction in neurone number in the jejunal myenteric plexus of the BAC group and the endocrine cell population (serotoninergic and argyrophilic cells) was significantly increased in this intestine segment. In conclusion, the present findings provide further evidence that the myenteric denervation induced by BAC may lead to the development of a local imbalance of the neurotransmitters, with a consequent induction of enteroendocrine cell (argyrophilic and serotoninergic cells) hyperplasia in the crypt and villus. PMID:10971748

Endocrine effects of prenatal exposure to PCBs, dioxins, and other xenobiotics: implications for policy and future research.

PubMed Central

Birnbaum, L S

1994-01-01

Recent reports have suggested that environmental chemicals may be associated with endocrine alterations in people, wildlife, and experimental animals. Pharmacological investigations as well as natural poisoning episodes have led to the association between exogenous chemicals and alterations in multiple hormonal systems. Persistent environmental contaminants such as dioxins and PCBs have been shown to modulate the activities of several different hormones. The unborn child or the neonate may be at special risk from these chemicals because of rapid growth and development, in addition to enhanced exposure. Because most exposure to these persistent chemicals is via food, changes in dietary habits and/or reduced contamination of the food supply may be required. PMID:7895708

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

... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OPPT-2010-0877; FRL-8849-8] Endocrine Disruptor Screening...-tiered paradigm for screening and testing chemicals for endocrine activity (i.e., estrogen, androgen, and... 5417), e.g., persons who conduct testing of chemical substances for endocrine effects. This listing is...

ENDOCRINE-DISRUPTING CHEMICALS: PREPUBERTAL EXPOSURES AND EFFECTS ON SEXUAL MATURATION AND THYROID FUNCTION IN THE MALE RAT. A FOCUS ON THE EDSTAC RECOMMENDATIONS. ENDOCRINE DISRUPTER SCREENING AND TESTING ADVISORY COMMITTEE

EPA Science Inventory

Endocrine-disrupting chemicals: prepubertal exposures and effects on sexual maturation and thyroid function in the male rat. A focus on the EDSTAC recommendations. Endocrine Disrupter Screening and Testing Advisory Committee.

Stoker TE, Parks LG, Gray LE, Cooper RL.

COMPARISON OF FATHEAD MINNOW AND HUMAN ESTROGEN RECEPTOR BINDING TO ENDOCRINE DISRUPTING COMPOUNDS

EPA Science Inventory

Environmental estrogens have the potential to disrupt endocrine function in a myriad of species. However, in vitro assays designed to detect and characterize endocrine disrupting chemicals (EDCs) typically utilize mammalian estrogen receptors. Our overall objective is to charac...

Endocrine Disrupting Chemicals Mediated through Binding Androgen Receptor Are Associated with Diabetes Mellitus

PubMed Central

Sakkiah, Sugunadevi; Wang, Tony; Zou, Wen; Wang, Yuping; Pan, Bohu; Tong, Weida; Hong, Huixiao

2017-01-01

Endocrine disrupting chemicals (EDCs) can mimic natural hormone to interact with receptors in the endocrine system and thus disrupt the functions of the endocrine system, raising concerns on the public health. In addition to disruption of the endocrine system, some EDCs have been found associated with many diseases such as breast cancer, prostate cancer, infertility, asthma, stroke, Alzheimer’s disease, obesity, and diabetes mellitus. EDCs that binding androgen receptor have been reported associated with diabetes mellitus in in vitro, animal, and clinical studies. In this review, we summarize the structural basis and interactions between androgen receptor and EDCs as well as the associations of various types of diabetes mellitus with the EDCs mediated through androgen receptor binding. We also discuss the perspective research for further understanding the impact and mechanisms of EDCs on the risk of diabetes mellitus. PMID:29295509

Fluoride caused thyroid endocrine disruption in male zebrafish (Danio rerio).

PubMed

Jianjie, Chen; Wenjuan, Xue; Jinling, Cao; Jie, Song; Ruhui, Jia; Meiyan, Li

2016-02-01

Excessive fluoride in natural water ecosystem has the potential to detrimentally affect thyroid endocrine system, but little is known of such effects or underlying mechanisms in fish. In the present study, we evaluated the effects of fluoride on growth performance, thyroid histopathology, thyroid hormone levels, and gene expressions in the HPT axis in male zebrafish (Danio rerio) exposed to different determined concentrations of 0.1, 0.9, 2.0 and 4.1 M of fluoride to investigate the effects of fluoride on thyroid endocrine system and the potential toxic mechanisms caused by fluoride. The results indicated that the growth of the male zebrafish used in the experiments was significantly inhibited, the thyroid microtrastructure was changed, and the levels of T3 and T4 were disturbed in fluoride-exposed male fish. In addition, the expressional profiles of genes in HPT axis displayed alteration. The expressions of all studied genes were significantly increased in all fluoride-exposed male fish after exposure for 45 days. The transcriptional levels of corticotrophin-releasing hormone (CRH), thyroid-stimulating hormone (TSH), thyroglobulin (TG), sodium iodide symporter (NIS), iodothyronine I (DIO1), and thyroid hormone receptor alpha (TRα) were also elevated in all fluoride-exposed male fish after 90 days of exposure, while the inconsistent expressions were found in the mRNA of iodothyronineⅡ (DIO2), UDP glucuronosyltransferase 1 family a, b (UGT1ab), transthyretin (TTR), and thyroid hormone receptor beta (TRβ). These results demonstrated that fluoride could notably inhibit the growth of zebrafish, and significantly affect thyroid endocrine system by changing the microtrastructure of thyroid, altering thyroid hormone levels and endocrine-related gene expressions in male zebrafish. All above indicated that fluoride could pose a great threat to thyroid endocrine system, thus detrimentally affected the normal function of thyroid of male zebrafish. Copyright © 2015

Endocrine resistance in breast cancer – an overview and update

PubMed Central

Clarke, Robert; Tyson, John J.; Dixon, J. Michael

2015-01-01

Tumors that express detectable levels of the product of the ESR1 gene (estrogen receptor-α; ERα) represent the single largest molecular subtype of breast cancer. More women eventually die from ERα+ breast cancer than from either HER2+ disease (almost half of which also express ERα) and/or from triple negative breast cancer (ERα-negative, progesterone receptor-negative, and HER2-negative). Antiestrogens and aromatase inhibitors are largely indistinguishable from each other in their abilities to improve overall survival and almost 50% of ERα+ breast cancers will eventually fail one or more of these endocrine interventions. The precise reasons why these therapies fail in ERα+ breast cancer remain largely unknown. Pharmacogenetic explanations for Tamoxifen resistance are controversial. The role of ERα mutations in endocrine resistance remains unclear. Targeting the growth factors and oncogenes most strongly correlated with endocrine resistance has proven mostly disappointing in their abilities to improve overall survival substantially, particularly in the metastatic setting. Nonetheless, there are new concepts in endocrine resistance that integrate molecular signaling, cellular metabolism, and stress responses including endoplasmic reticulum stress and the unfolded protein response (UPR) that provide novel insights and suggest innovative therapeutic targets. Encouraging evidence that drug combinations with CDK4/CDK6 inhibitors can extend recurrence free survival may yet translate to improvements in overall survival. Whether the improvements seen with immunotherapy in other cancers can be achieved in breast cancer remains to be determined, particularly for ERα+ breast cancers. This review explores the basic mechanisms of resistance to endocrine therapies, concluding with some new insights from systems biology approaches further implicating autophagy and the UPR in detail, and a brief discussion of exciting new avenues and future prospects. PMID:26455641

New insights into the endocrine disrupting effects of brominated flame retardants.

PubMed

Legler, Juliette

2008-09-01

The objective of this review is to provide an overview of recent studies demonstrating the endocrine disrupting (ED) effects of brominated flame retardants (BFRs), while highlighting interesting data presented at the recent international BFR workshop in Amsterdam in April, 2007. A review written in 2002 was used as a starting point and about 60 publications published since 2003 were reviewed. New insights into the in vivo effects of BFRs on thyroid hormone, estrogen and androgen pathways in both mammalian and non-mammalian models are provided, and novel (in vitro) findings on the mechanisms underlying ED effects are highlighted. Special attention is also given to reports on neurotoxicological effects at relatively low doses of BFRs, although an endocrine-related mechanism is disputable. Convincing evidence has been published showing that BFRs and importantly, BFR metabolites, have the potential to disrupt endocrine systems at multiple target sites. While some studies suggest a wide margin of safety between effect concentrations in rodent models and levels encountered in humans and the environment, other studies demonstrate that exposure to low doses relevant for humans and wildlife at critical time points in development can result in profound effects on both endocrine pathways and (neuro)development.

Review: the role of neural crest cells in the endocrine system.

PubMed

Adams, Meghan Sara; Bronner-Fraser, Marianne

2009-01-01

The neural crest is a pluripotent population of cells that arises at the junction of the neural tube and the dorsal ectoderm. These highly migratory cells form diverse derivatives including neurons and glia of the sensory, sympathetic, and enteric nervous systems, melanocytes, and the bones, cartilage, and connective tissues of the face. The neural crest has long been associated with the endocrine system, although not always correctly. According to current understanding, neural crest cells give rise to the chromaffin cells of the adrenal medulla, chief cells of the extra-adrenal paraganglia, and thyroid C cells. The endocrine tumors that correspond to these cell types are pheochromocytomas, extra-adrenal paragangliomas, and medullary thyroid carcinomas. Although controversies concerning embryological origin appear to have mostly been resolved, questions persist concerning the pathobiology of each tumor type and its basis in neural crest embryology. Here we present a brief history of the work on neural crest development, both in general and in application to the endocrine system. In particular, we present findings related to the plasticity and pluripotency of neural crest cells as well as a discussion of several different neural crest tumors in the endocrine system.

Career Advancement: Meeting the Challenges Confronting the Next Generation of Endocrinologists and Endocrine Researchers.

PubMed

Santen, Richard J; Joham, Anju; Fishbein, Lauren; Vella, Kristen R; Ebeling, Peter R; Gibson-Helm, Melanie; Teede, Helena

2016-12-01

Challenges and opportunities face the next generation (Next-Gen) of endocrine researchers and clinicians, the lifeblood of the field of endocrinology for the future. A symposium jointly sponsored by The Endocrine Society and the Endocrine Society of Australia was convened to discuss approaches to addressing the present and future Next-Gen needs. Data collection by literature review, assessment of previously completed questionnaires, commissioning of a new questionnaire, and summarization of symposium discussions were studied. Next-Gen endocrine researchers face diminishing grant funding in inflation-adjusted terms. The average age of individuals being awarded their first independent investigator funding has increased to age 45 years. For clinicians, a workforce gap exists between endocrinologists needed and those currently trained. Clinicians in practice are increasingly becoming employees of integrated hospital systems, resulting in greater time spent on nonclinical issues. Workforce data and published reviews identify challenges specifically related to early career women in endocrinology. Strategies to Address Issues: Recommendations encompassed the areas of grant support for research, mentoring, education, templates for career development, specific programs for Next-Gen members by senior colleagues as outlined in the text, networking, team science, and life/work integration. Endocrine societies focusing on Next-Gen members provide a powerful mechanism to support these critical areas. A concerted effort to empower, train, and support the next generation of clinical endocrinologists and endocrine researchers is necessary to ensure the viability and vibrancy of our discipline and to optimize our contributions to improving health outcomes. Collaborative engagement of endocrine societies globally will be necessary to support our next generation moving forward.

Prospective Trial of High-Dose Reirradiation Using Daily Image Guidance With Intensity-Modulated Radiotherapy for Recurrent and Second Primary Head-and-Neck Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Allen M., E-mail: allen.chen@ucdmc.ucdavis.edu; Farwell, D. Gregory; Luu, Quang

2011-07-01

Purpose: To report a single-institutional experience using intensity-modulated radiotherapy with daily image-guided radiotherapy for the reirradiation of recurrent and second cancers of the head and neck. Methods and Materials: Twenty-one consecutive patients were prospectively treated with intensity-modulated radiotherapy from February 2006 to March 2009 to a median dose of 66 Gy (range, 60-70 Gy). None of these patients received concurrent chemotherapy. Daily helical megavoltage CT scans were obtained before each fraction as part of an image-guided radiotherapy registration protocol for patient alignment. Results: The 1- and 2-year estimates of in-field control were 72% and 65%, respectively. A total of 651more » daily megavoltage CT scans were obtained. The mean systematic shift to account for interfraction motion was 1.38 {+-} 1.25 mm, 1.79 {+-} 1.45 mm, and 1.98 {+-} 1.75 mm for the medial-lateral, superior-inferior, and anterior-posterior directions, respectively. Pretreatment shifts of >3 mm occurred in 19% of setups in the medial-lateral, 27% in the superior-inferior, and 33% in the anterior-posterior directions, respectively. There were no treatment-related fatalities or hospitalizations. Complications included skin desquamation, odynophagia, otitis externa, keratitis, naso-lacrimal duct stenosis, and brachial plexopathy. Conclusions: Intensity-modulated radiotherapy with daily image guidance results in effective disease control with relatively low morbidity and should be considered for selected patients with recurrent and second primary cancers of the head and neck.« less

Phytosteroids Beyond Estrogens: Regulators of Reproductive and Endocrine Function in Natural Products

PubMed Central

Dean, Matthew; Murphy, Brian T.; Burdette, Joanna E.

2016-01-01

Foods and botanical supplements can interfere with the endocrine system through the presence of phytosteroids – chemicals that interact with steroids receptors. Phytoestrogens are well studied, but compounds such as kaempferol, apigenin, genistein, ginsenoside Rf, and glycyrrhetinic acid have been shown to interact with non-estrogen nuclear receptors. These compounds can have agonist, antagonist, or mixed agonist/antagonist activity depending on compound, receptor, cell line or tissue, and concentration. Some phytosteroids have also been shown to inhibit steroid metabolizing enzymes, resulting in biological effects through altered endogenous steroid concentrations. An interesting example, compound A (4-[1-chloro-2-(methylamino)ethyl]phenyl acetate hydrochloride (1:1)) is a promising selective glucocorticoid receptor modulator (SGRM) based on a phytosteroid isolated from Salsola tuberculatiformis Botschantzev. Given that $6.9 billion of herbal supplements are sold each year, is clear that further identification and characterization of phytosteroids is needed to ensure the safe and effective use of botanical supplements. PMID:27986590

Metabolic syndrome, endocrine disruptors and prostate cancer associations: biochemical and pathophysiological evidences

PubMed Central

Quagliariello, Vincenzo; Rossetti, Sabrina; Cavaliere, Carla; Di Palo, Rossella; Lamantia, Elvira; Castaldo, Luigi; Nocerino, Flavia; Ametrano, Gianluca; Cappuccio, Francesca; Malzone, Gabriella; Montanari, Micaela; Vanacore, Daniela; Romano, Francesco Jacopo; Piscitelli, Raffaele; Iovane, Gelsomina; Pepe, Maria Filomena; Berretta, Massimiliano; D'Aniello, Carmine; Perdonà, Sisto; Muto, Paolo; Botti, Gerardo; Ciliberto, Gennaro; Veneziani, Bianca Maria; De Falco, Francesco; Maiolino, Piera; Caraglia, Michele; Montella, Maurizio; Iaffaioli, Rosario Vincenzo; Facchini, Gaetano

2017-01-01

This review summarizes the main pathophysiological basis of the relationship between metabolic syndrome, endocrine disruptor exposure and prostate cancer that is the most common cancer among men in industrialized countries. Metabolic syndrome is a cluster of metabolic and hormonal factors having a central role in the initiation and recurrence of many western chronic diseases including hormonal-related cancers and it is considered as the worlds leading health problem in the coming years. Many biological factors correlate metabolic syndrome to prostate cancer and this review is aimed to focus, principally, on growth factors, cytokines, adipokines, central obesity, endocrine abnormalities and exposure to specific endocrine disruptors, a cluster of chemicals, to which we are daily exposed, with a hormone-like structure influencing oncogenes, tumor suppressors and proteins with a key role in metabolism, cell survival and chemo-resistance of prostate cancer cells. Finally, this review will analyze, from a molecular point of view, how specific foods could reduce the relative risk of incidence and recurrence of prostate cancer or inhibit the biological effects of endocrine disruptors on prostate cancer cells. On the basis of these considerations, prostate cancer remains a great health problem in terms of incidence and prevalence and interventional studies based on the treatment of metabolic syndrome in cancer patients, minimizing exposure to endocrine disruptors, could be a key point in the overall management of this disease. PMID:28389628

Metabolic syndrome, endocrine disruptors and prostate cancer associations: biochemical and pathophysiological evidences.

PubMed

Quagliariello, Vincenzo; Rossetti, Sabrina; Cavaliere, Carla; Di Palo, Rossella; Lamantia, Elvira; Castaldo, Luigi; Nocerino, Flavia; Ametrano, Gianluca; Cappuccio, Francesca; Malzone, Gabriella; Montanari, Micaela; Vanacore, Daniela; Romano, Francesco Jacopo; Piscitelli, Raffaele; Iovane, Gelsomina; Pepe, Maria Filomena; Berretta, Massimiliano; D'Aniello, Carmine; Perdonà, Sisto; Muto, Paolo; Botti, Gerardo; Ciliberto, Gennaro; Veneziani, Bianca Maria; De Falco, Francesco; Maiolino, Piera; Caraglia, Michele; Montella, Maurizio; Iaffaioli, Rosario Vincenzo; Facchini, Gaetano

2017-05-02

This review summarizes the main pathophysiological basis of the relationship between metabolic syndrome, endocrine disruptor exposure and prostate cancer that is the most common cancer among men in industrialized countries. Metabolic syndrome is a cluster of metabolic and hormonal factors having a central role in the initiation and recurrence of many western chronic diseases including hormonal-related cancers and it is considered as the world's leading health problem in the coming years. Many biological factors correlate metabolic syndrome to prostate cancer and this review is aimed to focus, principally, on growth factors, cytokines, adipokines, central obesity, endocrine abnormalities and exposure to specific endocrine disruptors, a cluster of chemicals, to which we are daily exposed, with a hormone-like structure influencing oncogenes, tumor suppressors and proteins with a key role in metabolism, cell survival and chemo-resistance of prostate cancer cells. Finally, this review will analyze, from a molecular point of view, how specific foods could reduce the relative risk of incidence and recurrence of prostate cancer or inhibit the biological effects of endocrine disruptors on prostate cancer cells. On the basis of these considerations, prostate cancer remains a great health problem in terms of incidence and prevalence and interventional studies based on the treatment of metabolic syndrome in cancer patients, minimizing exposure to endocrine disruptors, could be a key point in the overall management of this disease.

Elucidating the Links Between Endocrine Disruptors and Neurodevelopment

PubMed Central

Blawas, Ashley M.; Gray, Kimberly; Heindel, Jerrold J.; Lawler, Cindy P.

2015-01-01

Recent data indicate that approximately 12% of children in the United States are affected by neurodevelopmental disorders, including attention deficit hyperactivity disorder, learning disorders, intellectual disabilities, and autism spectrum disorders. Accumulating evidence indicates a multifactorial etiology for these disorders, with social, physical, genetic susceptibility, nutritional factors, and chemical toxicants acting together to influence risk. Exposure to endocrine-disrupting chemicals during the early stages of life can disrupt normal patterns of development and thus alter brain function and disease susceptibility later in life. This article highlights research efforts and pinpoints approaches that could shed light on the possible associations between environmental chemicals that act on the endocrine system and compromised neurodevelopmental outcomes. PMID:25714811

Review of Prader-Willi syndrome: the endocrine approach

PubMed Central

Heksch, Ryan; Kamboj, Manmohan; Anglin, Kathryn

2017-01-01

Prader-Willi syndrome (PWS) is a complex genetic disorder with implications on the endocrine and neurologic systems, metabolism, and behavior. Early in life, PWS is characterized by hypotonia and failure to thrive, followed by obesity and hyperphagia. Patients with PWS develop hypothalamic dysfunction which may lead growth hormone deficiency (GHD), hypogonadism, hypothyroidism, adrenal insufficiency, and poor bone mineral density (BMD). In addition to hypothalamic dysfunction, individuals with PWS have increased risk for obesity which may be complicated by metabolic syndrome and type 2 diabetes mellitus (T2DM). In this paper, we will review the current literature pertaining to the endocrine concerns of PWS and current recommendations for screening and management of these conditions. PMID:29184809

Glutamine-enriched enteral feeding in trauma patients: reduced infectious morbidity is not related to changes in endocrine and metabolic responses.

PubMed

Houdijk, A P; Nijveldt, R J; van Leeuwen, P A

1999-01-01

Recently we have shown that glutamine-enriched enteral nutrition in trauma patients reduced the occurrence of pneumonia, bacteremia, and sepsis. In that study, no clear explanation for these results was found except for lower tumor necrosis factor (TNF)-soluble receptors, suggesting immunomodulation. Here we present data on the course of endocrine and metabolic plasma mediators that were analyzed to provide more insight into the working mechanism of glutamine. Endocrine and metabolic mediators were measured in plasma samples taken on admission (day 0) and on days 1, 2, 3, 7, and 10. Glucose, prealbumin, albumin, alanine, C-reactive protein, alpha1-antitrypsin, complement factors, cortisol, glucagon, insulin, and growth hormone were assessed by standard techniques. The rate of feeding, demography, and injury severity did not differ between the glutamine and control group. There was a sustained hyperglycemic response in both groups. Insulin levels rose in the second phase of the period of observation. A moderate cortisol and glucagon response was seen in both groups. There was no alteration in growth hormone levels in either group. C-reactive protein, alpha1-antitrypsin, and complement factors showed similar increases in both groups but levels remained in the normal range. The course of alanine, albumin, and prealbumin also showed no difference between the groups. Glutamine-enriched enteral nutrition had no influence on the endocrine and metabolic response in trauma patients. Therefore, the reduction in infectious morbidity seen in glutamine-supplemented trauma patients is most likely not explained by a modulation of the humoral stress response and its metabolic consequences.

Secretion of pancreatic polypeptide in patients with pancreatic endocrine tumors.

PubMed

Adrian, T E; Uttenthal, L O; Williams, S J; Bloom, S R

1986-07-31

Pancreatic polypeptide is often secreted by pancreatic endocrine tumors and is considered a marker for such tumors. To investigate the diagnostic value of this marker, we studied 323 patients with proved pancreatic endocrine tumors. We found plasma concentrations of pancreatic polypeptide to be elevated (more than 300 pmol per liter) in 144 patients (diagnostic sensitivity, 45 percent). However, plasma levels of pancreatic polypeptide can also be elevated in the absence of a pancreatic tumor. To ascertain whether the administration of atropine could distinguish between normal and tumor-associated polypeptide secretion, we studied 30 patients with pancreatic tumors and high plasma levels of pancreatic polypeptide, 18 patients without tumors who had elevated levels of pancreatic polypeptide, and eight normal controls. Polypeptide levels in the 18 patients without tumors were substantially lower than in the 30 patients with tumors. Atropine (1 mg intramuscularly) did not suppress polypeptide levels in patients with tumors, but did suppress plasma levels by more than 50 percent in all subjects without tumors. Thus, although its diagnostic sensitivity is low, pancreatic polypeptide appears to be a useful adjunctive marker of many pancreatic endocrine tumors, and the atropine suppression test can be used to distinguish normal from tumor-related secretion of the polypeptide. Identification of the type of pancreatic endocrine tumor still requires measurement of the hormone that is specific for the tumor.

Modulation of gastrointestinal vagal neurocircuits by hyperglycemia

PubMed Central

Browning, Kirsteen N.

2013-01-01

Glucose sensing within autonomic neurocircuits is critical for the effective integration and regulation of a variety of physiological homeostatic functions including the co-ordination of vagally-mediated reflexes regulating gastrointestinal (GI) functions. Glucose regulates GI functions via actions at multiple sites of action, from modulating the activity of enteric neurons, endocrine cells, and glucose transporters within the intestine, to regulating the activity and responsiveness of the peripheral terminals, cell bodies and central terminals of vagal sensory neurons, to modifying both the activity and synaptic responsiveness of central brainstem neurons. Unsurprisingly, significant impairment in GI functions occurs in pathophysiological states where glucose levels are dysregulated, such as diabetes. A substantial obstacle to the development of new therapies to modify the disease, rather than treat the symptoms, are the gaps in our understanding of the mechanisms by which glucose modulates GI functions, particularly vagally-mediated responses and a more complete understanding of disease-related plasticity within these neurocircuits may open new avenues and targets for research. PMID:24324393

Endoplasmic Reticulum (ER) Stress and Endocrine Disorders

PubMed Central

Ariyasu, Daisuke; Yoshida, Hiderou; Hasegawa, Yukihiro

2017-01-01

The endoplasmic reticulum (ER) is the organelle where secretory and membrane proteins are synthesized and folded. Unfolded proteins that are retained within the ER can cause ER stress. Eukaryotic cells have a defense system called the “unfolded protein response” (UPR), which protects cells from ER stress. Cells undergo apoptosis when ER stress exceeds the capacity of the UPR, which has been revealed to cause human diseases. Although neurodegenerative diseases are well-known ER stress-related diseases, it has been discovered that endocrine diseases are also related to ER stress. In this review, we focus on ER stress-related human endocrine disorders. In addition to diabetes mellitus, which is well characterized, several relatively rare genetic disorders such as familial neurohypophyseal diabetes insipidus (FNDI), Wolfram syndrome, and isolated growth hormone deficiency type II (IGHD2) are discussed in this article. PMID:28208663

Gastroenteropancreatic (neuro)endocrine neoplasms: the histology report.

PubMed

Rindi, Guido; Bordi, C; La Rosa, S; Solcia, E; Delle Fave, Gianfranco

2011-03-01

Based on the year 2000 World Health Organization (WHO) classification and the European Neuroendocrine Tumor Society (ENETS) grading and staging proposals, we here define the minimal guidelines for pathology reporting of (neuro)endocrine neoplasms. The macroscopical description is recommended according to standard procedures and the microscopical description according to recognized architectural and cytological features for endocrine lesions. Minimal diagnostic immunohistochemistry entails the use of chromogranin A, synaptophysin and Ki67. Other potentially useful tests are those for CD56 N-CAM, PGP 9.5 and hormones for diagnosis, the somatostatin receptor subtype 2 for potential radiodiagnostics and therapy, and transcription factors like TTF1 and CDX2, for site of origin. Grading definition is always mandatory as well as TNM staging for surgical specimens. Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd.. All rights reserved.

Monogenic autoimmune diseases of the endocrine system.

PubMed

Johnson, Matthew B; Hattersley, Andrew T; Flanagan, Sarah E

2016-10-01

The most common endocrine diseases, type 1 diabetes, hyperthyroidism, and hypothyroidism, are the result of autoimmunity. Clustering of autoimmune endocrinopathies can result from polygenic predisposition, or more rarely, may present as part of a wider syndrome due to a mutation within one of seven genes. These monogenic autoimmune diseases show highly variable phenotypes both within and between families with the same mutations. The average age of onset of the monogenic forms of autoimmune endocrine disease is younger than that of the common polygenic forms, and this feature combined with the manifestation of other autoimmune diseases, specific hallmark features, or both, can inform clinicians as to the relevance of genetic testing. A genetic diagnosis can guide medical management, give an insight into prognosis, inform families of recurrence risk, and facilitate prenatal diagnoses. Copyright © 2016 Elsevier Ltd. All rights reserved.

A case report of mixed acinar-endocrine carcinoma of the pancreas treated with S-1 chemotherapy: Does it work or induce endocrine differentiation?

PubMed

Yokode, Masataka; Itai, Ryosuke; Yamashita, Yukimasa; Zen, Yoh

2017-11-01

Acinar cell carcinomas (ACCs) and mixed acinar-endocrine carcinomas (MAECs) of the pancreas are rare, accounting for only 1% of pancreatic tumors. Although both typically present at an advanced stage, chemotherapeutic regimes have not yet been standardized. A 65-year-old man presented with a large mass in the pancreatic tail with multiple liver metastases. He was initially treated with gemcitabine for suspected ductal carcinoma of the pancreas, but no response was observed. S-1, administered as second-line chemotherapy, showed an approximately 38% reduction in the size of the primary tumor and metastatic deposits with therapeutic effects being maintained for 12 months. When the tumor progressed again, he underwent a percutaneous liver biopsy, which led to the diagnosis of MAEC. Combination therapy with cisplatin and etoposide targeting the endocrine component was administered, and this was based on the endocrine component potentially being less sensitive to S-1 than the ACC element. However, therapy was stopped due to the development of neutropenia, and the patient is currently receiving best supportive care. Given the previous studies suggested that S-1 is more effective for ACCs than gemcitabine, MAECs may also respond to S-1 chemotherapy, similar to ACCs. Another potential interpretation is that S-1 was effective when the condition was ACC, and eventually showed decreased effectiveness when the condition shifted to MAEC. Future studies are needed to conclude whether S-1 chemotherapy truly works against MAECs or induces endocrine differentiation in ACCs as a part of the drug-resistance process.

Endocrine and Nutritional Management After Bariatric Surgery

MedlinePlus

... focus on the care patients need immediately after surgery, as well as long-term management to prevent complications and weight regain. How does ... index.cfm). www.hormone.org Endocrine and Nutritional Management After Bariatric Surgery Patient Guide November 2010

Endocrine Disruptor Screening Program Tier 1 Assessments

EPA Pesticide Factsheets

EPA has completed weight-of-evidence (WoE) assessments under the Endocrine Distruptor Screening Program (EDSP) for 52 pesticides included in the final list of chemicals for Tier 1 screening. See weight of evidence reports and data evaluation records.

In vivo reprogramming of pancreatic acinar cells to three islet endocrine subtypes

PubMed Central

Li, Weida; Nakanishi, Mio; Zumsteg, Adrian; Shear, Matthew; Wright, Christopher; Melton, Douglas A; Zhou, Qiao

2014-01-01

Direct lineage conversion of adult cells is a promising approach for regenerative medicine. A major challenge of lineage conversion is to generate specific cell subtypes. The pancreatic islets contain three major hormone-secreting endocrine subtypes: insulin+ β-cells, glucagon+ α-cells, and somatostatin+ δ-cells. We previously reported that a combination of three transcription factors, Ngn3, Mafa, and Pdx1, directly reprograms pancreatic acinar cells to β-cells. We now show that acinar cells can be converted to δ-like and α-like cells by Ngn3 and Ngn3+Mafa respectively. Thus, three major islet endocrine subtypes can be derived by acinar reprogramming. Ngn3 promotes establishment of a generic endocrine state in acinar cells, and also promotes δ-specification in the absence of other factors. δ-specification is in turn suppressed by Mafa and Pdx1 during α- and β-cell induction. These studies identify a set of defined factors whose combinatorial actions reprogram acinar cells to distinct islet endocrine subtypes in vivo. DOI: http://dx.doi.org/10.7554/eLife.01846.001 PMID:24714494

Meeting Report: Measuring Endocrine-Sensitive Endpoints within the First Years of Life

PubMed Central

Arbuckle, Tye E.; Hauser, Russ; Swan, Shanna H.; Mao, Catherine S.; Longnecker, Matthew P.; Main, Katharina M.; Whyatt, Robin M.; Mendola, Pauline; Legrand, Melissa; Rovet, Joanne; Till, Christine; Wade, Mike; Jarrell, John; Matthews, Stephen; Van Vliet, Guy; Bornehag, Carl-Gustaf; Mieusset, Roger

2008-01-01

An international workshop titled “Assessing Endocrine-Related Endpoints within the First Years of Life” was held 30 April–1 May 2007, in Ottawa, Ontario, Canada. Representatives from a number of pregnancy cohort studies in North America and Europe presented options for measuring various endocrine-sensitive endpoints in early life and discussed issues related to performing and using those measures. The workshop focused on measuring reproductive tract developmental endpoints [e.g., anogenital distance (AGD)], endocrine status, and infant anthropometry. To the extent possible, workshop participants strove to develop or recommend standardized measurements that would allow comparisons and pooling of data across studies. The recommended outcomes include thigh fat fold, breast size, vaginal cytology, AGD, location of the testis, testicular size, and growth of the penis, with most of the discussion focusing on the genital exam. Although a number of outcome measures recommended during the genital exam have been associated with exposure to endocrine-disrupting chemicals, little is known about how predictive these effects are of later reproductive health or other chronic health conditions. PMID:18629319

Endocrine disruption by dietary phyto-oestrogens: impact on dimorphic sexual systems and behaviours

PubMed Central

Patisaul, Heather B.

2017-01-01

A wide range of health benefits have been ascribed to soya intake including a lowered risk of osteoporosis, heart disease, breast cancer, and menopausal symptoms. Because it is a hormonally active diet, however, soya can also be endocrine disrupting, suggesting that intake has the potential to cause adverse health effects in certain circumstances, particularly when exposure occurs during development. Consequently, the question of whether or not soya phyto-oestrogens are beneficial or harmful to human health is neither straightforward nor universally applicable to all groups. Possible benefits and risks depend on age, health status, and even the presence or absence of specific gut microflora. As global consumption increases, greater awareness and consideration of the endocrine-disrupting properties of soya by nutrition specialists and other health practitioners is needed. Consumption by infants and small children is of particular concern because their hormone-sensitive organs, including the brain and reproductive system, are still undergoing sexual differentiation and maturation. Thus, their susceptibility to the endocrine-disrupting activities of soya phyto-oestrogens may be especially high. As oestrogen receptor partial agonists with molecular and cellular properties similar to anthropogenic endocrine disruptors such as bisphenol A, the soya phyto-oestrogens provide an interesting model for how attitudes about what is ‘synthetic’ v. what is ‘natural,’ shapes understanding and perception of what it means for a compound to be endocrine disrupting and/or potentially harmful. This review describes the endocrine-disrupting properties of soya phyto-oestrogens with a focus on neuroendocrine development and behaviour. PMID:27389644

Development of the Drosophila entero-endocrine lineage and its specification by the Notch signaling pathway

PubMed Central

Takashima, Shigeo; Adams, Katrina L.; Ortiz, Paola A.; Ying, Chong T.; Moridzadeh, Rameen; Younossi-Hartenstein, Amelia; Hartenstein, Volker

2013-01-01

In this paper we have investigated the developmental-genetic steps that shape the entero-endocrine system of Drosophila melanogaster from the embryo to the adult. The process starts in the endoderm of the early embryo where precursors of endocrine cells and enterocytes of the larval midgut, as well as progenitors of the adult midgut, are specified by a Notch signaling-dependent mechanism. In a second step that occurs during the late larval period, enterocytes and endocrine cells of a transient pupal midgut are selected from within the clusters of adult midgut progenitors. As in the embryo, activation of the Notch pathway triggers enterocyte differentiation, and inhibits cells from further proliferation or choosing the endocrine fate. The third step of entero-endocrine cell development takes place at a mid-pupal stage. Before this time point, the epithelial layer destined to become the adult midgut is devoid of endocrine cells. However, precursors of the intestinal midgut stem cells (pISCs) are already present. After an initial phase of symmetric divisions which causes an increase in their own population size, pISCs start to spin off cells that become postmitotic and express the endocrine fate marker, Prospero. Activation of Notch in pISCs forces these cells into an enterocyte fate. Loss of Notch function causes an increase in the proliferatory activity of pISCs, as well as a higher ratio of Prospero-positive cells. PMID:21382366

Using in Vitro High Throughput Screening Assays to Identify Potential Endocrine-Disrupting Chemicals

EPA Science Inventory

Over the past 20 years, an increased focus on detecting environmental chemicals posing a risk of adverse effects due to endocrine disruption has driven the creation of the U.S. EPA Endocrine Disruptor Screening Program (EDSP). Thousands of chemicals are subject to the EDSP, whic...

Human bone marrow-derived mesenchymal cells differentiate and mature into endocrine pancreatic lineage in vivo.

PubMed

Phadnis, Smruti M; Joglekar, Mugdha V; Dalvi, Maithili P; Muthyala, Sudhakar; Nair, Prabha D; Ghaskadbi, Surendra M; Bhonde, Ramesh R; Hardikar, Anandwardhan A

2011-03-01

The scarcity of human islets for transplantation remains a major limitation of cell replacement therapy for diabetes. Bone marrow-derived progenitor cells are of interest because they can be isolated, expanded and offered for such therapy under autologous/allogeneic settings. We characterized and compared human bone marrow-derived mesenchymal cells (hBMC) obtained from (second trimester), young (1-24 years) and adult (34-81 years) donors. We propose a novel protocol that involves assessment of paracrine factors from regenerating pancreas in differentiation and maturation of hBMC into endocrine pancreatic lineage in vivo. We observed that donor age was inversely related to growth potential of hBMC. Following in vitro expansion and exposure to specific growth factors involved in pancreatic development, hBMC migrated and formed islet-like cell aggregates (ICA). ICA show increased abundance of pancreatic transcription factors (Ngn3, Brn4, Nkx6.1, Pax6 and Isl1). Although efficient differentiation was not achieved in vitro, we observed significant maturation and secretion of human c-peptide (insulin) upon transplantation into pancreactomized and Streptozotocin (STZ)-induced diabetic mice. Transplanted ICA responded to glucose and maintained normoglycemia in diabetic mice. Our data demonstrate that hBMC have tremendous in vitro expansion potential and can be differentiated into multiple lineages, including the endocrine pancreatic lineage. Paracrine factors secreted from regenerating pancreas help in efficient differentiation and maturation of hBMC, possibly via recruiting chromatin modulators, to generate glucose-responsive insulin-secreting cells.

Selected endocrine disrupting compounds (vinclozolin, flutamide, ketoconazole and dicofol): effects on survival, occurrence of males, growth, molting and reproduction of Daphnia magna.

PubMed

Haeba, Maher H; Hilscherová, Klára; Mazurová, Edita; Bláha, Ludek

2008-05-01

Pollution-induced endocrine disruption in vertebrates and invertebrates is a worldwide environmental problem, but relatively little is known about effects of endocrine disrupting compounds (EDCs) in planktonic crustaceans (including Daphnia magna). Aims of the present study were to investigate acute 48 h toxicity and sub-chronic (4-6 days) and chronic (21 days) effects of selected EDCs in D. magna. We have investigated both traditional endpoints as well as other parameters such as sex determination, maturation, molting or embryogenesis in order to evaluate the sensitivity and possible use of these endpoints in ecological risk assessment. We have studied effects of four model EDCs (vinclozolin, flutamide, ketoconazole and dicofol) on D. magna using (i) an acute 48 h immobilization assay, (ii) a sub-chronic, 4-6 day assay evaluating development and the sex ratio of neonates, and (iii) a chronic, 21 day assay studying number of neonates, sex of neonates, molting frequency, day of maturation and the growth of maternal organisms. Acute EC50 values in the 48 h immobilization test were as follows (mg/L): dicofol 0.2, ketoconazole 1.5, flutamide 2.7, vinclozolin >3. Short-term, 4-6 day assays with sublethal concentrations showed that the sex ratio in Daphnia was modulated by vinclozolin (decreased number of neonate males at 1 mg/L) and dicofol (increase in males at 0.1 mg/L). Flutamide (up to 1 mg/L) had no effect on the sex of neonates, but inhibited embryonic development at certain stages during chronic assay, resulting in abortions. Ketoconazole had no significant effects on the studied processes up to 1 mg/L. Sex ratio modulations by some chemicals (vinclozolin and dicofol) corresponded to the known action of these compounds in vertebrates (i.e. anti-androgenicity and anti-oestrogenicity, respectively). Our study revealed that some chemicals known to affect steroid-regulated processes in vertebrates can also affect sublethal endpoints (e.g. embryonic sex determination

Concurrent endocrine neoplasias in dogs and cats: a retrospective study (2004-2014).

PubMed

Beatrice, Laura; Boretti, Felicitas Schär; Sieber-Ruckstuhl, Nadja S; Mueller, Claudia; Kümmerle-Fraune, Claudia; Hilbe, Monika; Grest, Paula; Reusch, Claudia E

2018-03-17

Multiple endocrine neoplasia (MEN) is a well-known syndrome in human medicine, whereas only a few cases of concurrent endocrine neoplasias have been reported in dogs and cats. The aim of this study was to evaluate the prevalence of concurrent endocrine neoplasias in dogs and cats at our clinic, identify possible breed and sex predispositions and investigate similarities with MEN syndromes in humans. Postmortem reports of 951 dogs and 1155 cats that died or were euthanased at the Clinic for Small Animal Internal Medicine, University of Zurich, between 2004 and 2014 were reviewed, and animals with at least two concurrent endocrine neoplasias and/or hyperplasias were included. Twenty dogs and 15 cats met the inclusion criteria. In dogs, the adrenal glands were most commonly affected. Multiple tumours affecting the adrenal glands and the association of these tumours with pituitary adenomas were the most common tumour combinations. Only one dog had a combination resembling human MEN type 1 syndrome (pituitary adenoma and insulinoma). In cats, the thyroid glands were most commonly affected and there were no similarities to human MEN syndromes. The prevalence of concurrent endocrine neoplasia was 2.1 per cent in dogs and 1.3 per cent in cats and MEN-like syndromes are very rare in these species. © British Veterinary Association (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Opposing actions of Arx and Pax4 in endocrine pancreas development

PubMed Central

Collombat, Patrick; Mansouri, Ahmed; Hecksher-Sørensen, Jacob; Serup, Palle; Krull, Jens; Gradwohl, Gerard; Gruss, Peter

2003-01-01

Genes encoding homeodomain-containing proteins potentially involved in endocrine pancreas development were isolated by combined in silico and nested-PCR approaches. One such transcription factor, Arx, exhibits Ngn3-dependent expression throughout endocrine pancreas development in α, β-precursor, and δ cells. We have used gene targeting in mouse embryonic stem cells to generate Arx loss-of-function mice. Arx-deficient animals are born at the expected Mendelian frequency, but develop early-onset hypoglycemia, dehydration, and weakness, and die 2 d after birth. Immunohistological analysis of pancreas from Arx mutants reveals an early-onset loss of mature endocrine α cells with a concomitant increase in β-and δ-cell numbers, whereas islet morphology remains intact. Our study indicates a requirement of Arx for α-cell fate acquisition and a repressive action on β-and δ-cell destiny, which is exactly the opposite of the action of Pax4 in endocrine commitment. Using multiplex reverse transcriptase PCR (RT-PCR), we demonstrate an accumulation of Pax4 and Arx transcripts in Arx and Pax4 mutant mice, respectively. We propose that the antagonistic functions of Arx and Pax4 for proper islet cell specification are related to the pancreatic levels of the respective transcripts. PMID:14561778

Opposing actions of Arx and Pax4 in endocrine pancreas development.

PubMed

Collombat, Patrick; Mansouri, Ahmed; Hecksher-Sorensen, Jacob; Serup, Palle; Krull, Jens; Gradwohl, Gerard; Gruss, Peter

2003-10-15

Genes encoding homeodomain-containing proteins potentially involved in endocrine pancreas development were isolated by combined in silico and nested-PCR approaches. One such transcription factor, Arx, exhibits Ngn3-dependent expression throughout endocrine pancreas development in alpha, beta-precursor, and delta cells. We have used gene targeting in mouse embryonic stem cells to generate Arx loss-of-function mice. Arx-deficient animals are born at the expected Mendelian frequency, but develop early-onset hypoglycemia, dehydration, and weakness, and die 2 d after birth. Immunohistological analysis of pancreas from Arx mutants reveals an early-onset loss of mature endocrine alpha cells with a concomitant increase in beta-and delta-cell numbers, whereas islet morphology remains intact. Our study indicates a requirement of Arx for alpha-cell fate acquisition and a repressive action on beta-and delta-cell destiny, which is exactly the opposite of the action of Pax4 in endocrine commitment. Using multiplex reverse transcriptase PCR (RT-PCR), we demonstrate an accumulation of Pax4 and Arx transcripts in Arx and Pax4 mutant mice, respectively. We propose that the antagonistic functions of Arx and Pax4 for proper islet cell specification are related to the pancreatic levels of the respective transcripts.

Identification of endocrine disrupting chemicals acting on human aromatase.

PubMed

Baravalle, Roberta; Ciaramella, Alberto; Baj, Francesca; Di Nardo, Giovanna; Gilardi, Gianfranco

2018-01-01

Human aromatase is the cytochrome P450 catalysing the conversion of androgens into estrogens playing a key role in the endocrine system. Due to this role, it is likely to be a target of the so-called endocrine disrupting chemicals, a series of compounds able to interfere with the hormone system with toxic effects. If on one side the toxicity of some compounds such as bisphenol A is well known, on the other side the toxic concentrations of such compounds as well as the effect of the many other molecules that are in contact with us in everyday life still need a deep investigation. The availability of biological assays able to detect the interaction of chemicals with key molecular targets of the endocrine system represents a possible solution to identify potential endocrine disrupting chemicals. Here the so-called alkali assay previously developed in our laboratory is applied to test the effect of different compounds on the activity of human aromatase. The assay is based on the detection of the alkali product that forms upon strong alkali treatment of the NADP + released upon enzyme turnover. Here it is applied on human aromatase and validated using anastrozole and sildenafil as known aromatase inhibitors. Out of the small library of compounds tested, resveratrol and ketoconazole resulted to inhibit aromatase activity, while bisphenol A and nicotine were found to exert an inhibitory effect at relatively high concentrations (100μM), and other molecules such as lindane and four plasticizers did not show any significant effect. These data are confirmed by quantification of the product estrone in the same reaction mixtures through ELISA. Overall, the results show that the alkali assay is suitable to screen for molecules that interfere with aromatase activity. As a consequence it can also be applied to other molecular targets of EDCs that use NAD(P)H for catalysis in a high throughput format for the fast screening of many different compounds as endocrine disrupting

Circadian, endocrine, and metabolic effects of prolonged bedrest: Two 56-day bedrest studies

NASA Technical Reports Server (NTRS)

Vernikos-Danellis, J.; Winget, C. M.; Leach, C. S.; Rambaut, P. C.

1974-01-01

Two bedrest studies of 56 days each have been conducted to evaluate the effects of prolonged bedrest on circadian synchrony and endocrine and metabolic function. Measurements included the pituitary-adrenal, thyroid, parathyroid, insulin-glucose-growth hormones, catecholamine excretion, body temperature, and heart rate. The results indicated that a rigorous regimen of exercise did not prevent the endocrine and metabolic effects of prolonged bedrest. Changes in circadian, endocrine, and metabolic functions in bedrest appear to be due to changes in hydrostatic pressure and lack of postural cues rather than to inactivity, confinement, or the bleeding schedule. Prolonged bedrest, particularly beyond 24 days, resulted in rhythm desynchronization in spite of well regulated light/dark cycles, temperature, humidity, activity, and meal times and meal composition and in increased lability of all endocrine parameter measured. It also resulted in an apparent insensitivity of the glucose response to insulin, of cortisol secretion to ACTH, and of growth hormone secretion to hypoglycemia.

Control of the annual cycle in birds: endocrine constraints and plasticity in response to ecological variability.

PubMed

Dawson, Alistair

2008-05-12

This paper reviews information from ecological and physiological studies to assess how extrinsic factors can modulate intrinsic physiological processes. The annual cycle of birds is made up of a sequence of life-history stages: breeding, moult and migration. Each stage has evolved to occur at the optimum time and to last for the whole duration of time available. Some species have predictable breeding seasons, others are more flexible and some breed opportunistically in response to unpredictable food availability. Photoperiod is the principal environmental cue used to time each stage, allowing birds to adapt their physiology in advance of predictable environmental changes. Physiological (neuroendocrine and endocrine) plasticity allows non-photoperiodic cues to modulate timing to enable individuals to cope with, and benefit from, short-term environmental variability. Although the timing and duration of the period of full gonadal maturation is principally controlled by photoperiod, non-photoperiodic cues, such as temperature, rainfall or food availability, could potentially modulate the exact time of breeding either by fine-tuning the time of egg-laying within the period of full gonadal maturity or, more fundamentally, by modulating gonadal maturation and/or regression. The timing of gonadal regression affects the time of the start of moult, which in turn may affect the duration of the moult. There are many areas of uncertainty. Future integrated studies are required to assess the scope for flexibility in life-history strategies as this will have a critical bearing on whether birds can adapt sufficiently rapidly to anthropogenic environmental changes, in particular climate change.

Epigenetic Transgenerational Effects of Endocrine Disruptors on Male Reproduction

PubMed Central

Guerrero-Bosagna, Carlos M.; Skinner, Michael K.

2013-01-01

Endocrine-disrupting chemicals generally function as steroid receptor signaling antagonists or agonists that influence development to promote adult-onset disease. Exposure to the endocrine disruptors during the initiation of male reproductive tract development interferes with the normal hormonal signaling and formation of male reproductive organs. In particular, exposure to the endocrine disruptor vinclozolin promotes transgenerational transmission of adult-onset disease states such as male infertility, increased frequencies of tumors, prostate disease, kidney diseases, and immune abnormalities that develop as males age. An epigenetic change in the germ line would be involved in the transgenerational transmission of these induced phenotypes. Nevertheless, other studies have also reported transgenerational transmission of induced epigenetic changes, without altering the germ line. Here we propose a nomenclature to help clarify both cases of transgenerational epigenetic transmission. An intrinsic epigenetic transgenerational process would require a germ-line involvement, a permanent alteration in the germ cell epigenome, and only one exposure to the environmental factor. An extrinsic epigenetic transgenerational process would involve an epigenetic alteration in a somatic tissue and require exposure at each generation to maintain the transgenerational phenotype. PMID:19711250

Traumatic Brain Injury: Effects on the Endocrine System

MedlinePlus

Fact Sheet BTrarainumInajutircy: Effects on the Endocrine System What is traumatic brain injury? Traumatic brain injury, also called TBI, is sudden damage to the brain. It happens when the head hits ...

Consensus models to predict endocrine disruption for all ...

EPA Pesticide Factsheets

Humans are potentially exposed to tens of thousands of man-made chemicals in the environment. It is well known that some environmental chemicals mimic natural hormones and thus have the potential to be endocrine disruptors. Most of these environmental chemicals have never been tested for their ability to disrupt the endocrine system, in particular, their ability to interact with the estrogen receptor. EPA needs tools to prioritize thousands of chemicals, for instance in the Endocrine Disruptor Screening Program (EDSP). Collaborative Estrogen Receptor Activity Prediction Project (CERAPP) was intended to be a demonstration of the use of predictive computational models on HTS data including ToxCast and Tox21 assays to prioritize a large chemical universe of 32464 unique structures for one specific molecular target – the estrogen receptor. CERAPP combined multiple computational models for prediction of estrogen receptor activity, and used the predicted results to build a unique consensus model. Models were developed in collaboration between 17 groups in the U.S. and Europe and applied to predict the common set of chemicals. Structure-based techniques such as docking and several QSAR modeling approaches were employed, mostly using a common training set of 1677 compounds provided by U.S. EPA, to build a total of 42 classification models and 8 regression models for binding, agonist and antagonist activity. All predictions were evaluated on ToxCast data and on an exte

Endocrine manifestations and management of Prader-Willi syndrome.

PubMed

Emerick, Jill E; Vogt, Karen S

2013-08-21

Prader-Willi syndrome (PWS) is a complex genetic disorder, caused by lack of expression of genes on the paternally inherited chromosome 15q11.2-q13. In infancy it is characterized by hypotonia with poor suck resulting in failure to thrive. As the child ages, other manifestations such as developmental delay, cognitive disability, and behavior problems become evident. Hypothalamic dysfunction has been implicated in many manifestations of this syndrome including hyperphagia, temperature instability, high pain threshold, sleep disordered breathing, and multiple endocrine abnormalities. These include growth hormone deficiency, central adrenal insufficiency, hypogonadism, hypothyroidism, and complications of obesity such as type 2 diabetes mellitus. This review summarizes the recent literature investigating optimal screening and treatment of endocrine abnormalities associated with PWS, and provides an update on nutrition and food-related behavioral intervention. The standard of care regarding growth hormone therapy and surveillance for potential side effects, the potential for central adrenal insufficiency, evaluation for and treatment of hypogonadism in males and females, and the prevalence and screening recommendations for hypothyroidism and diabetes are covered in detail. PWS is a genetic syndrome in which early diagnosis and careful attention to detail regarding all the potential endocrine and behavioral manifestations can lead to a significant improvement in health and developmental outcomes. Thus, the important role of the provider caring for the child with PWS cannot be overstated.

CHARACTERIZATION OF ENDOCRINE-DISRUPTION AND CLINICAL MANIFESTATIONS IN LARGE-MOUTH BASS FROM FLORIDA LAKES

EPA Science Inventory

Previous efforts from this laboratory, have documented altered endocrine function and sexual differentiation for alligators and turtles from Lake Apopka in Central Florida. This lake has been exposed to a variety of contaminants which are potentially endocrine-disrupting. Therefo...

Applications of genomic medicine in endocrinology and post-genomic endocrine research.

PubMed

Stratakis, Constantine A

2005-01-01

In the mid 1980's, two advances revolutionized Medicine in a way that is comparable only to some of the most important events in the approximately 3,000 years of its history. The first was the introduction of the concept of "positional cloning", i.e. the idea that one can identify genes for human disease though knowing nothing or very little about their function. The second was the discovery of the method of polymerase chain reaction (PCR) which made DNA easier to work with for all biomedical researchers and clinicians. Fresh in the history of Endocrinology were the great discoveries of neuroendocrinology, and even more contemporary and potent, the influence of the then emerging field of molecular endocrinology. Cancer medicine and traditional human genetics were the fields that benefited most from the first applications of the new genomic concepts and technologies. Almost two decades later, and after the first successful applications of positional cloning in Endocrine Genetics with the identification of RET, menin, PTEN and PRKAR1A in the various forms of multiple endocrine tumor syndromes, and a number of other genes in developmental diseases affecting the pituitary, thyroid, parathyroid, pancreas, adrenal and gonadal glands, endocrinology has made a comeback to the forefront of "genomically"- influenced as well as post-genomic Medicine. This report, using the example of endocrine tumor genetics, presents the process and some of the accomplishments of positional cloning and discusses the influence of endocrinology on contemporary translational research. The author suggests that some of the most traditional endocrine concepts, established in the previous two centuries, could help us understand the complex pathways recently unraveled in cancer genetics and, consequently, other fields. It is suggested that "Endocrine" genes that control cellular signaling act as "conductor" since they regulate differentiation, growth and proliferation. Their complex function and

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

2016-03-25

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.

Neuroendocrine disruption without direct endocrine mode of action: Polychloro-biphenyls (PCBs) and bisphenol A (BPA) as case studies.

PubMed

Pinson, Anneline; Franssen, Delphine; Gérard, Arlette; Parent, Anne-Simone; Bourguignon, Jean-Pierre

Endocrine disruption is commonly thought to be restricted to a direct endocrine mode of action i.e. the perturbation of the activation of a given type of hormonal receptor by its natural ligand. Consistent with the WHO definition of an endocrine disrupter, a key issue is the "altered function(s) of the endocrine system". Such altered functions can result from different chemical interactions, beyond agonistic or antagonistic effect at a given receptor. Based on neuroendocrine disruption by polychlorinated biphenyls and bisphenol A, this paper proposes different mechanistic paradigms that can result in adverse health effects. They are a consequence of altered endocrine function(s) secondary to chemical interaction with different steps in the physiological regulatory processes, thus accounting for a possibly indirect endocrine mode of action. Copyright © 2017 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.

Growth and endocrine disorders in thalassemia: The international network on endocrine complications in thalassemia (I-CET) position statement and guidelines

PubMed Central

De Sanctis, Vincenzo; Soliman, Ashraf T.; Elsedfy, Heba; Skordis, Nicos; Kattamis, Christos; Angastiniotis, Michael; Karimi, Mehran; Yassin, Mohd Abdel Daem Mohd; El Awwa, Ahmed; Stoeva, Iva; Raiola, Giuseppe; Galati, Maria Concetta; Bedair, Elsaid M.; Fiscina, Bernadette; El Kholy, Mohamed

2013-01-01

The current management of thalassemia includes regular transfusion programs and chelation therapy. It is important that physicians be aware that endocrine abnormalities frequently develop mainly in those patients with significant iron overload due to poor compliance to treatment, particularly after the age of 10 years. Since the quality of life of thalassemia patients is a fundamental aim, it is vital to monitor carefully their growth and pubertal development in order to detect abnormalities and to initiate appropriate and early treatment. Abnormalities should be identified and treatment initiated in consultation with a pediatric or an adult endocrinologist and managed accordingly. Appropriate management shall put in consideration many factors such as age, severity of iron overload, presence of chronic liver disease, thrombophilia status, and the presence of psychological problems. All these issues must be discussed by the physician in charge of the patient's care, the endocrinologist and the patient himself. Because any progress in research in the field of early diagnosis and management of growth disorders and endocrine complications in thalassemia should be passed on to and applied adequately to all those suffering from the disease, on the 8 May 2009 in Ferrara, the International Network on Endocrine Complications in Thalassemia (I-CET) was founded in order to transmit the latest information on these disorders to the treating physicians. The I-CET position statement outlined in this document applies to patients with transfusion-dependent thalassemia major to help physicians to anticipate, diagnose, and manage these complications properly. PMID:23776848

In Vitro Effects of the Endocrine Disruptor p,p'-DDT on Human Follitropin Receptor.

PubMed

Munier, Mathilde; Grouleff, Julie; Gourdin, Louis; Fauchard, Mathilde; Chantreau, Vanessa; Henrion, Daniel; Coutant, Régis; Schiøtt, Birgit; Chabbert, Marie; Rodien, Patrice

2016-07-01

1-chloro-4-[2,2,2-trichloro-1-(4-chlorophenyl)ethyl]benzene (p,p'-DDT) is a persistent environmental endocrine disruptor (ED). Several studies have shown an association between p,p'-DDT exposure and reproductive abnormalities. To investigate the putative effects of p,p'-DDT on the human follitropin receptor (FSHR) function. We used Chinese hamster ovary (CHO) cells stably expressing human FSHR to investigate the impact of p,p'-DDT on FSHR activity and its interaction with the receptor. At a concentration of 5 μM p,p'-DDT increased the maximum response of the FSHR to follitropin by 32 ± 7.45%. However, 5 μM p,p'-DDT decreased the basal activity and did not influence the maximal response of the closely related LH/hCG receptor to human chorionic gonadotropin (hCG). The potentiating effect of p,p'-DDT was specific for the FSHR. Moreover, in cells that did not express FSHR, p,p'-DDT had no effect on cAMP response. Thus, the potentiating effect of p,p'-DDT was dependent on the FSHR. In addition, p,p'-DDT increased the sensitivity of FSHR to hCG and to a low molecular weight agonist of the FSHR, 3-((5methyl)-2-(4-benzyloxy-phenyl)-5-{[2-[3-ethoxy-4-methoxy-phenyl)-ethylcarbamoyl]-methyl}-4-oxo-thiazolidin-3-yl)-benzamide (16a). Basal activity in response to p,p'-DDT and potentiation of the FSHR response to FSH by p,p'-DDT varied among FSHR mutants with altered transmembrane domains (TMDs), consistent with an effect of p,p'-DDT via TMD binding. This finding was corroborated by the results of simultaneously docking p,p'-DDT and 16a into the FSHR transmembrane bundle. p,p'-DDT acted as a positive allosteric modulator of the FSHR in our experimental model. These findings suggest that G protein-coupled receptors are additional targets of endocrine disruptors. Munier M, Grouleff J, Gourdin L, Fauchard M, Chantreau V, Henrion D, Coutant R, Schiøtt B, Chabbert M, Rodien P. 2016. In vitro effects of the endocrine disruptor p,p'-DDT on human follitropin receptor. Environ Health

Adjuvant endocrine therapy for premenopausal women with hormone-responsive breast cancer.

PubMed

Mathew, Aju; Davidson, Nancy E

2015-11-01

Multiple strategies for endocrine treatment of premenopausal women with hormone-responsive breast cancer have been assessed and results have been presented over the last two years. These include tamoxifen for 5-10 years (ATLAS and aTTom), tamoxifen for 5 years followed by aromatase inhibitor (AI) for 5 years for women who have become postmenopausal (MA-17); ovarian ablation (OA) by surgery (EBCTCG overview); ovarian function suppression (OFS) by LHRH agonist (LHRH agonist meta-analysis); or combinations of approaches including OFS plus tamoxifen or AI (SOFT, TEXT, ABCSG 12 and E3193). Many of these trials have taken place in the backdrop of (neo)adjuvant chemotherapy which can confound interpretation because such therapy can suppress ovarian function either transiently or permanently. Nonetheless these trials suggest in aggregate that 10 years of tamoxifen are better than 5 years and that a program of extended adjuvant therapy of tamoxifen for 5 years followed by aromatase inhibitor for 5 years is effective for suitable candidates. The SOFT and E3193 trials do not show a major advantage for use of OFS + tamoxifen compared to tamoxifen alone. The joint SOFT/TEXT analysis and ABCGS12 trials both suggest that outcomes can be excellent with the use of combined endocrine therapy alone in properly selected patients but give conflicting results with regard to potential benefits for OFS + AI compared with OFS + tamoxifen. Further work will be needed to ascertain long-term outcomes, identify factors that predict who will benefit from extended adjuvant endocrine therapy, and assess role of OFS by medical or surgical means. It is clear, however, that endocrine therapy is a critical part of the adjuvant regimen for most premenopausal women with hormone-responsive breast cancer, and a subset of these women with luminal A-type tumors can be safely treated with endocrine therapy alone. Copyright © 2015 Elsevier Ltd. All rights reserved.

The international spinal cord injury endocrine and metabolic function basic data set.

PubMed

Bauman, W A; Biering-Sørensen, F; Krassioukov, A

2011-10-01

To develop the International Spinal Cord Injury (SCI) Endocrine and Metabolic Function Basic Data Set within the framework of the International SCI Data Sets that would facilitate consistent collection and reporting of basic endocrine and metabolic findings in the SCI population. International. The International SCI Endocrine and Metabolic Function Data Set was developed by a working group. The initial data set document was revised on the basis of suggestions from members of the Executive Committee of the International SCI Standards and Data Sets, the International Spinal Cord Society (ISCoS) Executive and Scientific Committees, American Spinal Injury Association (ASIA) Board, other interested organizations and societies, and individual reviewers. In addition, the data set was posted for 2 months on ISCoS and ASIA websites for comments. The final International SCI Endocrine and Metabolic Function Data Set contains questions on the endocrine and metabolic conditions diagnosed before and after spinal cord lesion. If available, information collected before injury is to be obtained only once, whereas information after injury may be collected at any time. These data include information on diabetes mellitus, lipid disorders, osteoporosis, thyroid disease, adrenal disease, gonadal disease and pituitary disease. The question of gonadal status includes stage of sexual development and that for females also includes menopausal status. Data will be collected for body mass index and for the fasting serum lipid profile. The complete instructions for data collection and the data sheet itself are freely available on the websites of ISCoS (http://www.iscos.org.uk) and ASIA (http://www.asia-spinalinjury.org).

Marital Conflict and Endocrine Function: Are Men Really More Physiologically Affected than Women?.

ERIC Educational Resources Information Center

Kiecolt-Glaser, Janice K.; And Others

1996-01-01

Assessed marital conflict and endocrine function in 90 newlywed couples. Blood samples were examined to provide composite and daytime values for three stress hormones and three related hormones. Data provided a window on endocrine function in couples for whom the day included conflicts. Discusses findings in the context of gender models of marital…

Overcoming Endocrine Resistance by Targeting ER/FoxA1/IL 8 Axis

DTIC Science & Technology

2016-10-01

INTRODUCTION Approximately 75% of breast cancers express the hormone estrogen receptor α (ER). As a critical determinant in estrogen response and oncogenic...factor of estrogen receptor α (ER)–chromatin binding and function, yet its aberration in endocrine-resistant (Endo-R) breast cancer is unknown. Here, we...positive tumors. FOXA1 | estrogen receptor | breast cancer | transcriptional reprogramming | endocrine resistance About 75% of breast cancers express

Endocrine tumors of the duodenum. A study of 55 cases relative to clinicopathological features and hormone content.

PubMed

Heymann, M F; Hamy, A; Triau, S; Miraillé, E; Toquet, C; Chomarat, H; Cohen, C; Maitre, F; Le Bodie, M F

2004-01-01

Study of prognosis of duodenal endocrine tumors. Retrospective study concerned 55 duodenal endocrine tumors discovered in biopsy or surgical specimens. Follow-up records available for 49 patients indicated that inconspicuous associated clinical manifestations were often found subsequently. Seven patients were classified as Zollinger-Ellison syndrome and seven as multiple endocrine neoplasia (6 MEN I and 1 MEN II). Tumors were small (mean 1.28cm) and located preferentially in the first and second part of the duodenum. Fifty-four were well-differentiated and one poorly differentiated. Immunochemistry revealed 30 G-cell tumors (54.6%), 15 D-cell (27.3%), two plurihormonal (EC cell and G cell), and one GRH-cell, whereas seven could not be classified. Fifteen patients died (five in relation to their disease). Twenty-one had metastases (liver, nodes, lung), eight of whom are still alive. Eighty-eight percent of duodenal endocrine tumors were gastrinomas, small plurifocal tumors and somatostatinomas preferentially located in the ampullar region and diagnosed because of hematemesis or icterus. Size is an important prognostic factor in determining whether surgery is required. The prognosis is better for D- and G-cell tumors than pancreatic endocrine tumors. Duodenal endocrine tumors in multiple endocrine neoplasia have a good prognosis, but can be associated with pancreatic plurihormonal tumors and metastases.

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 ...

Acromegaly: an endocrine society clinical practice guideline.

PubMed

Katznelson, Laurence; Laws, Edward R; Melmed, Shlomo; Molitch, Mark E; Murad, Mohammad Hassan; Utz, Andrea; Wass, John A H

2014-11-01

The aim was to formulate clinical practice guidelines for acromegaly. The Task Force included a chair selected by the Endocrine Society Clinical Guidelines Subcommittee (CGS), five experts in the field, and a methodologist. The authors received no corporate funding or remuneration. This guideline is cosponsored by the European Society of Endocrinology. This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. The Task Force reviewed primary evidence and commissioned two additional systematic reviews. One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society and the European Society of Endocrinology reviewed drafts of the guidelines. Using an evidence-based approach, this acromegaly guideline addresses important clinical issues regarding the evaluation and management of acromegaly, including the appropriate biochemical assessment, a therapeutic algorithm, including use of medical monotherapy or combination therapy, and management during pregnancy.

Endocrine Activity of Extraembryonic Membranes Extends beyond Placental Amniotes

PubMed Central

Albergotti, Lori C.; Hamlin, Heather J.; McCoy, Michael W.; Guillette,, Louis J.

2009-01-01

Background During development, all amniotes (mammals, reptiles, and birds) form extraembryonic membranes, which regulate gas and water exchange, remove metabolic wastes, provide shock absorption, and transfer maternally derived nutrients. In viviparous (live-bearing) amniotes, both extraembryonic membranes and maternal uterine tissues contribute to the placenta, an endocrine organ that synthesizes, transports, and metabolizes hormones essential for development. Historically, endocrine properties of the placenta have been viewed as an innovation of placental amniotes. However, an endocrine role of extraembryonic membranes has not been investigated in oviparous (egg-laying) amniotes despite similarities in their basic structure, function, and shared evolutionary ancestry. In this study, we ask whether the oviparous chorioallantoic membrane (CAM) of chicken (Gallus gallus) has the capability to synthesize and receive signaling of progesterone, a major placental steroid hormone. Methodology/Principal Findings We quantified mRNA expression of key steroidogenic enzymes involved in progesterone synthesis and found that 3β-hydroxysteroid dehydrogenase, which converts pregnenolone to progesterone exhibited a 464 fold increase in the CAM from day 8 to day 18 of embryonic development (F5, 68 = 89.282, p<0.0001). To further investigate progesterone synthesis, we performed explant culture and found that the CAM synthesizes progesterone in vitro in the presence of a steroid precursor. Finally, we quantified mRNA expression and performed protein immunolocalization of the progesterone receptor in the CAM. Conclusions/Significance Collectively, our data indicate that the chick CAM is steroidogenic and has the capability to both synthesize progesterone and receive progesterone signaling. These findings represent a paradigm shift in evolutionary reproductive biology by suggesting that endocrine activity of extraembryonic membranes is not a novel characteristic of placental

Endocrine Disruptors and Asthma-Associated Chemicals in Consumer Products

PubMed Central

Nishioka, Marcia; Standley, Laurel J.; Perovich, Laura J.; Brody, Julia Green; Rudel, Ruthann A.

2012-01-01

Background: Laboratory and human studies raise concerns about endocrine disruption and asthma resulting from exposure to chemicals in consumer products. Limited labeling or testing information is available to evaluate products as exposure sources. Objectives: We analytically quantified endocrine disruptors and asthma-related chemicals in a range of cosmetics, personal care products, cleaners, sunscreens, and vinyl products. We also evaluated whether product labels provide information that can be used to select products without these chemicals. Methods: We selected 213 commercial products representing 50 product types. We tested 42 composited samples of high-market-share products, and we tested 43 alternative products identified using criteria expected to minimize target compounds. Analytes included parabens, phthalates, bisphenol A (BPA), triclosan, ethanolamines, alkylphenols, fragrances, glycol ethers, cyclosiloxanes, and ultraviolet (UV) filters. Results: We detected 55 compounds, indicating a wide range of exposures from common products. Vinyl products contained > 10% bis(2-ethylhexyl) phthalate (DEHP) and could be an important source of DEHP in homes. In other products, the highest concentrations and numbers of detects were in the fragranced products (e.g., perfume, air fresheners, and dryer sheets) and in sunscreens. Some products that did not contain the well-known endocrine-disrupting phthalates contained other less-studied phthalates (dicyclohexyl phthalate, diisononyl phthalate, and di-n-propyl phthalate; also endocrine-disrupting compounds), suggesting a substitution. Many detected chemicals were not listed on product labels. Conclusions: Common products contain complex mixtures of EDCs and asthma-related compounds. Toxicological studies of these mixtures are needed to understand their biological activity. Regarding epidemiology, our findings raise concern about potential confounding from co-occurring chemicals and misclassification due to variability in

Mixed acinar-endocrine carcinoma of the pancreas: new clinical and pathological features in a contemporary series.

PubMed

Yu, Run; Jih, Lily; Zhai, Jing; Nissen, Nicholas N; Colquhoun, Steven; Wolin, Edward; Dhall, Deepti

2013-04-01

The objective of this study was to characterize the novel clinical and pathological features of mixed acinar-endocrine carcinoma of the pancreas. This was a retrospective review of medical records and surgical pathology specimens of patients with a diagnosis of mixed acinar-endocrine carcinoma of the pancreas at Cedars-Sinai Medical Center between 2005 and 2011. Additional immunohistochemistry was performed on the specimens of some patients. Five patients were identified. The median age at presentation was 74 years (range, 59-89 years), and all patients were male. The presenting symptoms were all related to tumor mass effects. The median size of the tumor was 10 cm (range, 3.9-16 cm). Preoperative clinical diagnosis aided by fine-needle aspiration biopsy was incorrect in all 5 cases. Most tumors (3/5) exhibited predominantly endocrine differentiation without hormonal production. Only 10% to 30% of cells were truly amphicrine, whereas most were differentiated into either endocrine or acinar phenotype. The clinical behavior ranged from moderate to aggressive with postoperative survival from 2.5 months to more than 3 years. Four patients received neoadjuvant or adjuvant chemotherapy with variable responses. Mixed acinar-endocrine carcinoma of the pancreas appears to be not uncommon in men, may harbor predominantly endocrine component, is often misdiagnosed by cytology, and exhibits variable clinical behavior. Mixed acinar-endocrine carcinoma of the pancreas should be considered in older patients with sizable pancreatic mass and may warrant aggressive surgical resection and chemotherapy.

Endocrine and metabolic assessment in adults with Langerhans cell histiocytosis.

PubMed

Montefusco, L; Harari, S; Elia, D; Rossi, A; Specchia, C; Torre, O; Adda, G; Arosio, M

2018-05-01

Diabetes insipidus (DI) is one of most common complications of Langerhans cell histiocytosis (LCH) but prevalence of anterior pituitary deficiencies and metabolic alterations have not been clearly defined yet. Evaluate prevalence of endocrine and metabolic manifestations in a cohort of patients affected by Pulmonary LCH. Observational cross-sectional study on 18 adults (7 M/11 F, 42±12years) studied for complete basal and dynamic endocrine lab tests and glucose metabolism. Hypothalamic-pituitary endocrine alterations were found in 9 patients: 9 had DI, 5 Growth Hormone Deficiency (GHD), 5 central hypogonadism, 3 central hypothyroidism and 1 central hypoadrenalism. Hyperprolactinemia and hypothalamic syndrome were found in 2 patients each. All these central endocrine alterations were always associated to DI. Five of the 10 MRI performed showed abnormalities. Prevalence of obesity and glucose alterations (either DM or IFG/IGT) were respectively 39% and 33%, higher than expected basing on epidemiological data on general Italian population. Multi-system-LCH without risk-organ involvement (LCH MS-RO - ) seems to have slightly higher prevalence of insulin resistance, glucose alterations and metabolic syndrome than LCH with isolated lung involvement (LCH SS lung + ). A papillary BRAFV600E positive thyroid carcinoma was diagnosed in one patient. The presence of anterior pituitary deficiencies should be systematically sought in all LCH patients with DI both at diagnosis and during the follow-up by basal and dynamic hormonal assessment. Patients with pulmonary LCH, particularly those with MS disease, have a worse metabolic profile than general population. Occurrence of papillary thyroid carcinoma has been reported. Copyright © 2017. Published by Elsevier B.V.

EG-VEGF: a key endocrine factor in placental development.

PubMed

Brouillet, Sophie; Hoffmann, Pascale; Feige, Jean-Jacques; Alfaidy, Nadia

2012-10-01

Endocrine gland-derived vascular endothelial growth factor (EG-VEGF), also named prokineticin 1, is the canonical member of the prokineticin family. Numerous reports suggest a direct involvement of this peptide in normal and pathological reproductive processes. Recent advances propose EG-VEGF as a key endocrine factor that controls many aspects of placental development and suggest its involvement in the development of preeclampsia (PE), the most threatening pathology of human pregnancy. This review describes the finely tuned action and regulation of EG-VEGF throughout human pregnancy, argues for its clinical relevance as a potential diagnostic marker of the onset of PE, and discusses future research directions for therapeutic targeting of EG-VEGF. Copyright © 2012 Elsevier Ltd. All rights reserved.

Endocrine and metabolic changes in payload specialist (L-1)

NASA Technical Reports Server (NTRS)

Matsui, Nobuo

1993-01-01

The endocrine system plays an important role in the adaptation to unusual environments by secreting hormones to control metabolism. Since human beings have long evolved on the surface of the Earth under a gravity environment, the weightless environment must be quite unusual for them. The purpose of this experiment is to study the mechanisms of human adaptation to a weightless environment from endocrine and metabolic changes. Our study plan is focused on four major physiological changes which were reported during past space flights or which may be expected to occur under that condition: (1) hormone and metabolic changes associated with fluid shift; (2) bone demineralization and muscle atrophy; (3) altered circadian rhythm; and (4) stress reaction during space flight.

Use and Effectiveness of Adjuvant Endocrine Therapy for Hormone Receptor-Positive Breast Cancer in Men.

PubMed

Venigalla, Sriram; Carmona, Ruben; Guttmann, David M; Jain, Varsha; Freedman, Gary M; Clark, Amy S; Shabason, Jacob E

2018-05-24

Although adjuvant endocrine therapy confers a survival benefit among females with hormone receptor (HR)-positive breast cancer, the effectiveness of this treatment among males with HR-positive breast cancer has not been rigorously investigated. To investigate trends, patterns of use, and effectiveness of adjuvant endocrine therapy among men with HR-positive breast cancer. This retrospective cohort study identified patients in the National Cancer Database with breast cancer who had received treatment from 2004 through 2014. Inclusion criteria for the primary study cohort were males at least 18 years old with nonmetastatic HR-positive invasive breast cancer who underwent surgery with or without adjuvant endocrine therapy. A cohort of female patients was also identified using the same inclusion criteria for comparative analyses by sex. Data analysis was conducted from October 1, 2017, to December 15, 2017. Receipt of adjuvant endocrine therapy. Patterns of adjuvant endocrine therapy use were assessed using multivariable logistic regression analyses. Association between adjuvant endocrine therapy use and overall survival was assessed using propensity score-weighted multivariable Cox regression models. The primary study cohort comprised 10 173 men with HR-positive breast cancer (mean [interquartile range] age, 66 [57-75] years). The comparative cohort comprised 961 676 women with HR-positive breast cancer (mean [interquartile range] age, 62 [52-72] years). The median follow-up for the male cohort was 49.6 months (range, 0.1-142.5 months). Men presented more frequently than women with HR-positive disease (94.0% vs 84.3%, P < .001). However, eligible men were less likely than women to receive adjuvant endocrine therapy (67.3% vs 79.0%; OR, 0.61; 95% CI, 0.58-0.63; P < .001). Treatment at academic facilities (odds ratio, 1.13; 95% CI, 1.02-1.25; P = .02) and receipt of adjuvant radiotherapy (odds ratio, 2.83; 95% CI, 2.55-3.15; P < .001) or chemotherapy

Determination of endocrine-disrupting chemicals in human milk by dispersive liquid-liquid microextraction.

PubMed

Vela-Soria, Fernando; Jiménez-Díaz, Inmaculada; Díaz, Caridad; Pérez, José; Iribarne-Durán, Luz María; Serrano-López, Laura; Arrebola, Juan Pedro; Fernández, Mariana Fátima; Olea, Nicolás

2016-09-01

Human populations are widely exposed to numerous so-called endocrine-disrupting chemicals, exogenous compounds able to interfere with the endocrine system. This exposure has been associated with several health disorders. New analytical procedures are needed for biomonitoring these xenobiotics in human matrices. A quick and inexpensive methodological procedure, based on sample treatment by dispersive liquid-liquid microextraction, is proposed for the determination of bisphenols, parabens and benzophenones in samples. LOQs ranged from 0.4 to 0.7 ng ml(-1) and RSDs from 4.3 to 14.8%. This methodology was satisfactorily applied in the simultaneous determination of a wide range of endocrine-disrupting chemicals in human milk samples and is suitable for application in biomonitoring studies.

Overcoming Endocrine Resistance by Targeting ER/FoxA1/IL-8 Axis

DTIC Science & Technology

2015-10-01

residual disease after 6-month neoadjuvant endocrine therapy 45 . Recent studies unveiled gain-of- function mutations in ESR1 , the gene encoding ER...described previously 61 . SYBR dye (Life Technologies) was used in real- time PCR and the target primer sequences are as follows: ESR1 forward...Breast Cancer Symposium (ed^(eds). Cancer Res (2013). 46. Li S, et al. Endocrine-therapy-resistant ESR1 variants revealed by genomic characterization of

[Vitamin D and endocrine diseases].

PubMed

Schuch, Natielen Jacques; Garcia, Vivian Cristina; Martini, Ligia Araújo

2009-07-01

Vitamin D insufficiency/deficiency has been worldwide reported in all age groups in recent years. It has been considered a Public Health matter since decreased levels of vitamin D has been related to several chronic diseases, as type 2 diabetes mellitus (T2DM), obesity and hypertension. Glucose intolerance and insulin secretion has been observed during vitamin D deficiency, both in animals and humans resulting in T2DM. The supposed mechanism underlying these findings is presence of vitamin D receptor in several tissues and cells, including pancreatic beta-cells, adipocyte and muscle cells. In obese individuals, the impaired vitamin D endocrine system, characterized by high levels of PTH and 1,25(OH)(2)D(3) could induce a negative feedback for the hepatic synthesis of 25(OH)D and also contribute to a higher intracellular calcium, which in turn secrete less insulin and deteriorate insulin sensitivity. In hypertension, vitamin D could act on renin-angiotensin system and also in vascular function. Administration of 1,25(OH)(2)D(3) could decreases renin gene expression and inhibit vascular smooth muscle cell proliferation. However, prospective and intervention human studies that clearly demonstrates the benefits of vitamin D status adequacy in the prevention and treatment of endocrine metabolic diseases are lacking. Further research still necessary to assure the maximum benefit of vitamin D in such situations.

Construction and application of a bovine immune-endocrine cDNA microarray.

PubMed

Tao, Wenjing; Mallard, Bonnie; Karrow, Niel; Bridle, Byram

2004-09-01

A variety of commercial DNA arrays specific for humans and rodents are widely available; however, microarrays containing well-characterized genes to study pathway-specific gene expression are not as accessible for domestic animals, such as cattle, sheep and pigs. Therefore, a small-scale application-targeted bovine immune-endocrine cDNA array was developed to evaluate genetic pathways involved in the immune-endocrine axis of cattle during periods of altered homeostasis provoked by physiological or environmental stressors, such as infection, vaccination or disease. For this purpose, 167 cDNA sequences corresponding to immune, endocrine and inflammatory response genes were collected and categorized. Positive controls included 5 housekeeping genes (glyceraldehydes-3-phosphate dehydrogenase, hypoxanthine phosphoribosyltransferase, ribosomal protein L19, beta-actin, beta2-microglobulin) and bovine genomic DNA. Negative controls were a bacterial gene (Rhodococcus equi 17-kDa virulence-associated protein) and a partial sequence of the plasmid pACYC177. In addition, RNA extracted from un-stimulated, as well as superantigen (Staphylococcus aureus enterotoxin-A, S. aureus Cowan Pansorbin Cells) and mitogen-stimulated (LPS, ConA) bovine blood leukocytes was mixed, reverse transcribed and PCR amplified using gene-specific primers. The endocrine-associated genes were amplified from cDNA derived from un-stimulated bovine hypothalamus, pituitary, adrenal and thyroid gland tissues. The array was constructed in 4 repeating grids of 180 duplicated spots by coupling the PCR amplified 213-630 bp gene fragments onto poly-l-lysine coated glass slides. The bovine immune-endocrine arrays were standardized and preliminary gene expression profiles generated using Cy3 and Cy5 labelled cDNA from un-stimulated and ConA (5 microg/ml) stimulated PBMC of 4 healthy Holstein cows (2-4 replicate arrays/cow) in a time course study. Mononuclear cell-derived cytokine and chemokine (IL-2, IL-1alpha

Bird populations as sentinels of endocrine disrupting chemicals.

PubMed

Carere, Claudio; Costantini, David; Sorace, Alberto; Santucci, Daniela; Alleva, Enrico

2010-01-01

Exposure to endocrine disrupting chemicals (EDCs) is a widespread phenomenon in nature. Although the mechanisms of action of EDCs are actively studied, the consequences of endocrine disruption (ED) at the population level and the adaptations evolved to cope with chronic EDC exposure have been overlooked. Birds probably represent the animal taxon most successfully adapted to synanthropic life. Hence, birds share with humans a similar pattern of exposure to xenobiotics. In this article, we review case studies on patterns of behaviour that deviate from the expectation in bird species exposed to EDCs. We provide behavioural and ecological parameters to be used as endpoints of ED; methodological requirements and caveats based on species-specific life-history traits, behavioural repertoires, developmental styles, and possibility of captive breeding; a list of species that could be used as sentinels to assess the quality of man-made environment.

Endocrine disruption: In silico interactions between phthalate plasticizers and corticosteroid binding globulin.

PubMed

Sheikh, Ishfaq A; Beg, Mohd A

2017-12-01

Endocrine disruption is a phenomenon when a man-made or natural compound interferes with normal hormone function in human or animal body systems. Endocrine-disrupting compounds (EDCs) have assumed considerable importance as a result of industrial activity, mass production of synthetic chemicals and environmental pollution. Phthalate plasticizers are a group of chemicals used widely and diversely in industry especially in the plastic industry, and many of the phthalate compounds have endocrine-disrupting properties. Increasing evidence indicates that steroid nuclear receptors and steroid binding proteins are the main targets of endocrine disruption. Corticosteroid-binding globulin (CBG) is a steroid binding protein that binds and transports cortisol in the blood circulation and is a potential target for endocrine disruption. An imbalance of cortisol in the body leads to many health problems. Induced fit docking of nine important and environmentally relevant phthalate plasticizers (DMP, BBP, DBP, DIBP, DnHP, DEHP, DINP, DnOP, DIDP) showed interactions with 10-19 amino acid residues of CBG. Comparison of the interacting residues of CBG with phthalate ligands and cortisol showed an overlapping of the majority (53-82%) of residues for each phthalate. Five of nine phthalate compounds and cortisol shared a hydrogen bonding interaction with the Arg-252 residue of CBG. Long-chain phthalates, such as DEHP, DINP, DnOP and DIDP displayed a higher binding affinity and formed a number of interactions with CBG in comparison to short-chain phthalates. The similarity in structural binding characteristics of phthalate compounds and native ligand cortisol suggested potential competitive conflicts in CBG-cortisol binding function and possible disruption of cortisol and progesterone homeostasis. Copyright © 2017 John Wiley & Sons, Ltd.

Current limitations and recommendations to improve testing for the environmental assessment of endocrine active substances

USGS Publications Warehouse

Coady, Katherine K.; Biever, Ronald C.; Denslow, Nancy D.; Gross, Melanie; Guiney, Patrick D.; Holbech, Henrik; Karouna-Renier, Natalie K.; Katsiadaki, Ioanna; Krueger, Hank; Levine, Steven L.; Maack, Gerd; Williams, Mike; Wolf, Jeffrey C.; Ankley, Gerald T.

2017-01-01

In the present study, existing regulatory frameworks and test systems for assessing potential endocrine active chemicals are described, and associated challenges are discussed, along with proposed approaches to address these challenges. Regulatory frameworks vary somewhat across geographies, but all basically evaluate whether a chemical possesses endocrine activity and whether this activity can result in adverse outcomes either to humans or to the environment. Current test systems include in silico, in vitro, and in vivo techniques focused on detecting potential endocrine activity, and in vivo tests that collect apical data to detect possible adverse effects. These test systems are currently designed to robustly assess endocrine activity and/or adverse effects in the estrogen, androgen, and thyroid hormone signaling pathways; however, there are some limitations of current test systems for evaluating endocrine hazard and risk. These limitations include a lack of certainty regarding: 1) adequately sensitive species and life stages; 2) mechanistic endpoints that are diagnostic for endocrine pathways of concern; and 3) the linkage between mechanistic responses and apical, adverse outcomes. Furthermore, some existing test methods are resource intensive with regard to time, cost, and use of animals. However, based on recent experiences, there are opportunities to improve approaches to and guidance for existing test methods and to reduce uncertainty. For example, in vitro high-throughput screening could be used to prioritize chemicals for testing and provide insights as to the most appropriate assays for characterizing hazard and risk. Other recommendations include adding endpoints for elucidating connections between mechanistic effects and adverse outcomes, identifying potentially sensitive taxa for which test methods currently do not exist, and addressing key endocrine pathways of possible concern in addition to those associated with estrogen, androgen, and thyroid

Application of Adverse Outcome Pathways to U.S. EPA’s Endocrine Disruptor Screening Program

PubMed Central

Noyes, Pamela D.; Casey, Warren M.; Dix, David J.

2017-01-01

Background: The U.S. EPA’s Endocrine Disruptor Screening Program (EDSP) screens and tests environmental chemicals for potential effects in estrogen, androgen, and thyroid hormone pathways, and it is one of the only regulatory programs designed around chemical mode of action. Objectives: This review describes the EDSP’s use of adverse outcome pathway (AOP) and toxicity pathway frameworks to organize and integrate diverse biological data for evaluating the endocrine activity of chemicals. Using these frameworks helps to establish biologically plausible links between endocrine mechanisms and apical responses when those end points are not measured in the same assay. Results: Pathway frameworks can facilitate a weight of evidence determination of a chemical’s potential endocrine activity, identify data gaps, aid study design, direct assay development, and guide testing strategies. Pathway frameworks also can be used to evaluate the performance of computational approaches as alternatives for low-throughput and animal-based assays and predict downstream key events. In cases where computational methods can be validated based on performance, they may be considered as alternatives to specific assays or end points. Conclusions: A variety of biological systems affect apical end points used in regulatory risk assessments, and without mechanistic data, an endocrine mode of action cannot be determined. Because the EDSP was designed to consider mode of action, toxicity pathway and AOP concepts are a natural fit. Pathway frameworks have diverse applications to endocrine screening and testing. An estrogen pathway example is presented, and similar approaches are being used to evaluate alternative methods and develop predictive models for androgen and thyroid pathways. https://doi.org/10.1289/EHP1304 PMID:28934726

BIOMARKERS OF ENDOCRINE DISRUPTION AT THE MRNA LEVEL

EPA Science Inventory

Denslow, Nancy D., Christopher J. Bowman, Gillian Robinson, H. Stephen Lee, Ronald J. Ferguson, Michael J. Hemmer and Leroy C. Folmar. 1999. Biomarkers of Endocrine Disruption at the mRNA Level. In: Environmental Toxicology and Risk Assessment: Standardization of Biomarkers for ...

Endocrine and metabolic disorders associated with human immune deficiency virus infection.

PubMed

Unachukwu, C N; Uchenna, D I; Young, E E

2009-01-01

Many reports have described endocrine and metabolic disorders in the human immunodeficiency virus (HIV) infection. This article reviewed various reports in the literature in order to increase the awareness and thus the need for early intervention when necessary. Data were obtained from MEDLINE, Google search and otherjournals on 'HIV, Endocrinopathies/Metabolic Disorders' from 1985 till 2007. Studies related to HIV associated endocrinopathies and metabolic disorders in the last two decades were reviewed. Information on epidemiology, pathogenesis, diagnosis and treatment of the target organ endocrinopathies and metabolic disorders in HIV/AIDS were extracted from relevant literature. Endocrine and metabolic disturbances occur in the course of HIV infection. Pathogenesis includes direct infection of endocrine glands by HIV or opportunistic organisms, infiltration by neoplasms and side effects of drugs. Adrenal insufficiency is the commonest HIV endocrinopathy with cytomegalovirus adrenalitis occurring in 40-88% of cases. Thyroid dysfunction may occur as euthyroid sick syndrome or sub-clinical hypothyroidism. Hypogonadotrophic dysfunction accounts for 75% of HIV-associated hypogonadism, with prolonged amenorrhoea being three times more likely in the women. Pancreatic dysfunction may result in hypoglycaemia or diabetes mellitus (DM). Highly active antiretroviral therapy (HAART) especially protease inhibitors has been noted to result in insulin resistance and lipodystrophy. Virtually every endocrine organ is involved in the course of HIV infection. Detailed endocrinological and metabolic evaluation and appropriate treatment is necessary in the optimal management of patients with HIV infection in our environment.

RESEARCH ON ENDOCRINE DISRUPTERS IN THE AQUATIC ENVIRONMENT BY THE UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

EPA Science Inventory

Research on Endocrine Disrupters in the Aquatic Environment by the United States Environmental Protection Agency (Abstract). Presented at the Endocrine Disrupters Workshop sponsored by the UK Department of Environment, Food and Rural Affairs, 8-9 September 2001, Weymouth, UK. 1 p...

In Silico Identification and Pharmacological Evaluation of Novel Endocrine Disrupting Chemicals That Act via the Ligand-Binding Domain of the Estrogen Receptor α

PubMed Central

Kufareva, Irina; Abagyan, Ruben

2014-01-01

Endocrine disrupting chemicals (EDCs) pose a significant threat to human health, society, and the environment. Many EDCs elicit their toxic effects through nuclear hormone receptors, like the estrogen receptor α (ERα). In silico models can be used to prioritize chemicals for toxicological evaluation to reduce the amount of costly pharmacological testing and enable early alerts for newly designed compounds. However, many of the current computational models are overly dependent on the chemistry of known modulators and perform poorly for novel chemical scaffolds. Herein we describe the development of computational, three-dimensional multi-conformational pocket-field docking, and chemical-field docking models for the identification of novel EDCs that act via the ligand-binding domain of ERα. These models were highly accurate in the retrospective task of distinguishing known high-affinity ERα modulators from inactive or decoy molecules, with minimal training. To illustrate the utility of the models in prospective in silico compound screening, we screened a database of over 6000 environmental chemicals and evaluated the 24 top-ranked hits in an ERα transcriptional activation assay and a differential scanning fluorimetry-based ERα binding assay. Promisingly, six chemicals displayed ERα agonist activity (32nM–3.98μM) and two chemicals had moderately stabilizing effects on ERα. Two newly identified active compounds were chemically related β-adrenergic receptor (βAR) agonists, dobutamine, and ractopamine (a feed additive that promotes leanness in cattle and poultry), which are the first βAR agonists identified as activators of ERα-mediated gene transcription. This approach can be applied to other receptors implicated in endocrine disruption. PMID:24928891

Twenty-Five Years of Endocrine Disruption Science: Remembering Theo Colborn

PubMed Central

Kwiatkowski, Carol F.; Bolden, Ashley L.; Liroff, Richard A.; Rochester, Johanna R.; Vandenbergh, John G.

2016-01-01

Summary: For nearly 30 years, Dr. Theo Colborn (1927–2014) dedicated herself to studying the harmful effects of endocrine-disrupting chemicals on wildlife, humans, and the environment. More recently, she extended this effort to address the health impacts of unconventional oil and gas development. Colborn was a visionary leader who excelled at synthesizing scientific findings across disciplines. Using her unique insights and strong moral convictions, she changed the face of toxicological research, influenced chemical regulatory policy, and educated the public. In 2003, Colborn started a nonprofit organization—The Endocrine Disruption Exchange (TEDX). As we celebrate the 25th anniversary of endocrine disruption science, TEDX continues her legacy of analyzing the extensive body of environmental health research and developing unique educational resources to support public policy and education. Among other tools, TEDX currently uses the systematic review framework developed by the National Toxicology Program at the National Institute of Environmental Health Sciences, to answer research questions of pressing concern. In this article, we pay homage to the tenacious woman and the exemplary contribution she made to the field of environmental health. Recommendations for the future of the field are drawn from her wisdom. PMID:27580976

Effects of long-term endocrine disrupting compound exposure on Macaca mulatta embryonic stem cells

PubMed Central

Midic, Uros; Vincent, Kailey A.; VandeVoort, Catherine A; Latham, Keith E.

2016-01-01

Endocrine disrupting chemicals (EDCs) exert significant effects on health and physiology, many traceable to effects on stem cell programming underlying development. Understanding risk of low-level, chronic EDC exposure will be enhanced by knowledge of effects on stem cells. We exposed rhesus monkey embryonic stem cells to low levels of five EDCs [bisphenol A (BPA), atrazine (ATR), tributyltin (TBT), perfluorooctanoic acid (PFOA), and di-(2-ethylhexyl) phthalate (DEHP)] for 28 days, and evaluated effects on gene expression by RNAseq transcriptome profiling. We observed little effect of BPA, and small numbers of affected genes (≤119) with other EDCs. There was substantial overlap in effects across two, three, or four treatments. Ingenuity Pathway analysis indicated suppression of cell survival genes and genes downstream of several stress response mediators, activation of cell death genes, and modulations in several genes regulating pluripotency, differentiation, and germ layer development. Potential adverse effects of these changes on development are discussed. PMID:27614199

Effects of long-term endocrine disrupting compound exposure on Macaca mulatta embryonic stem cells.

PubMed

Midic, Uros; Vincent, Kailey A; VandeVoort, Catherine A; Latham, Keith E

2016-10-01

Endocrine disrupting chemicals (EDCs) exert significant effects on health and physiology, many traceable to effects on stem cell programming underlying development. Understanding risk of low-level, chronic EDC exposure will be enhanced by knowledge of effects on stem cells. We exposed rhesus monkey embryonic stem cells to low levels of five EDCs [bisphenol A (BPA), atrazine (ATR), tributyltin (TBT), perfluorooctanoic acid (PFOA), and di-(2-ethylhexyl) phthalate (DEHP)] for 28days, and evaluated effects on gene expression by RNAseq transcriptome profiling. We observed little effect of BPA, and small numbers of affected genes (≤119) with other EDCs. There was substantial overlap in effects across two, three, or four treatments. Ingenuity Pathway analysis indicated suppression of cell survival genes and genes downstream of several stress response mediators, activation of cell death genes, and modulations in several genes regulating pluripotency, differentiation, and germ layer development. Potential adverse effects of these changes on development are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

[Synergistic effect of cell kinetics-directed chemo-endocrine therapy on experimental mammary tumors].

PubMed

Ueki, H

1987-11-01

We tried to demonstrate that the cell kinetics-directed chemoendocrine therapy is more effective on hormone dependent breast cancer than empirical combination of the endocrine therapy and chemotherapy. Cell kinetics of each tumor was measured by flow cytometric analysis. Estrogen dependent human breast cancer cell line MCF-7 was used in vitro. In vivo, androgen dependent SC-115 carcinoma was transplanted to DDS mice. In vitro, tamoxifen was administered as the endocrine therapy. In vivo, we carried out testectomy on DDS mice. Effect of the endocrine therapy on the cell kinetics of the tumor was thought to be G1-S depression. High density 5FU was administered as the chemotherapeutic agents, whose content was 1 microgram/ml in vitro and 40 mg/kg in vivo. 5FU brought temporary decrease of cells in S phase. Only anteceding 5FU administration had synergistic effect in combination of 5FU and the endocrine therapy. 5FU was convinced to act more effectively on cells in S phase, so it was shown that cell kinetics-directed schedule was superior to the empirical treatment schedule in chemoendocrine therapy.

Valine Supplementation in a Reduced Protein Diet Regulates Growth Performance Partially through Modulation of Plasma Amino Acids Profile, Metabolic Responses, Endocrine, and Neural Factors in Piglets.

PubMed

Zhang, Xiaoya; Liu, Xutong; Jia, Hongmin; He, Pingli; Mao, Xiangbing; Qiao, Shiyan; Zeng, Xiangfang

2018-03-28

The objective of this study was to investigate whether valine (Val) supplementation in a reduced protein (RP) diet regulates growth performance associated with the changes in plasma amino acids (AAs) profile, metabolism, endocrine, and neural system in piglets. Piglets or piglets with a catheter in the precaval vein were randomly assigned to two treatments, including two RP diets with standardized ileal digestible (SID) Val:Lysine (Lys) ratio of 0.45 and 0.65, respectively. The results indicated that piglets in the higher Val:Lys ratio treatment had higher average daily feed intake (ADFI) ( P < 0.001), average daily gain (ADG) ( P = 0.001), feed conversion ratio (FCR) ( P = 0.004), lower plasma urea nitrogen ( P = 0.032), expression of gastric cholecystokinin (CCK), and hypothalamic pro-opiomelanocortin (POMC). Plasma AAs profiles including postprandial plasma essential AAs (EAAs) profile and in serum, muscle, and liver involved in metabolism of AAs and fatty acids were significantly different between two treatments. In conclusion, Val influenced growth performance associated with metabolism of AAs and fatty acids and both endocrine and neural system in piglets.

Prostaglandins E and F in endocrine diarrheagenic syndromes.

PubMed Central

Jaffe, B M; Condon, S

1976-01-01

The role of prostaglandins in endocrine diarrheagenic syndromes was evaluated by measuring peripheral concentration of immunoreactive PGE and PGF in patients with non-endocrine diarrhea as well as those with the Zollinger-Ellison (Z-E) syndrome, MCT, carcinoid tumors and the WDHA syndrome. In 21 normals, PGE and PGF levels averaged 272 +/- 18 and 119 +/- 14 pg/ml, respectively. Twenty eight patients with diarrhea of non-endocrine origin (mainly inflammatory bowel disease) had levels indistinguishable from normal, i.e. 353 +/- 25 and 77 +/- 37 pg/ml, respectively. Among 29 patients with the Zollinger-Ellison syndrome (mean gastrin 6127 +/- 3267 pg/ml) only 2 had significantly elevated PGE levels; mean PGE levels, 382 +/- 32 pg/ml, were not significantly different from normal and did not correlate with either diarrhea or the serum gastrin concentration. In contrast, 18 of 22 patients with carcinoid tumors (mean blood serotonin concentration 1655 +/- 604 ng/ml; mean urinary excretion of 5 HIAA 66.8 +/- 16.7 mg/day) had elevated peripheral concentrations of PGE. The mean PGE level (1367 +/- 245 pg/ml) was significantly elevated (P less than 0.001). Nonetheless PGE levels did not correlate with diarrhea, blood concentrations of serotonin, or urinary indole excretion. MCT (mean serum calcitonin 24.5 +/- 6.3 ng/ml) was similarly associated with consistent (18/19) elevation in peripheral concentrations of PGE (mean 1922 +/- 541 pg/ml; P less than 0.001). Inthis syndrome, PGE levels were higher in patients with diarrhea and in those with markedly elevated serum thyrocalcitonin levels. Finally, 8 of 21 patients with the WDHA syndrome had increased levels of PGE. Although 13 of 17 patients had high levels of VIP (mean 8133 pg/ml), 2 patients had hyperprostaglandinemia in the face of normal peripheral concentrations of VIP. In one patient the serum PGE level was elevated prior to resection of the primary pancreatic neoplasm (9939 pg/ml) as well as the subsequent extirpation of

Evaluation of non-genomic, clinical risk and survival results in endocrine-sensitive, HER-2 negative, node negative breast cancer.

PubMed

Baena Cañada, José M; Gámez Casado, Salvador; Rodríguez Pérez, Lourdes; Quílez Cutillas, Alicia; Cortés Carmona, Cristina; Rosado Varela, Petra; Estalella Mendoza, Sara; Ramírez Daffós, Patricia; Benítez Rodríguez, Encarnación

2018-02-28

In endocrine-sensitive, HER-2 negative, node negative breast cancer, the presence of a low genomic risk allows treatment with adjuvant endocrine therapy alone, obtaining excellent survival rates. The justification for this study is to show that excellent survival rates are also obtained by treating with adjuvant hormone therapy alone, based on clinical risk assessment. A descriptive, observational and retrospective study was performed between 2006 and 2016 with endocrine-sensitive, HER-2 negative, node negative breast cancer, greater than 1cm or between 0.6 and 1cm with unfavourable features. Retrospective review of health records. Mortality data of the National Registry of Deaths. A total of 203 patients were evaluable for survival. One hundred and twenty-three (60.50%) were treated with adjuvant endocrine therapy alone, 77 (37.90%) with chemotherapy and endocrine therapy, one (0.50%) with chemotherapy alone and 2 (1%) were not treated. The overall survival rate at 5 years was 97% (95% confidence interval [CI] 94-100). Distant recurrence-free interval was 94% (95% CI 90-98). In the subgroup of patients treated with endocrine therapy alone, overall survival and distant recurrence-free interval rates at 5 years were 98% (95% CI 95-100) and 97% (95% CI 93-100), respectively. Patients with endocrine-sensitive, HER-2-negative, node negative breast cancer treated with endocrine therapy alone according to their clinical risk have similar survival outcomes as those treated with endocrine therapy according to their genomic risk. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

European Union's strategy on endocrine disrupting chemicals and the current position of Slovenia.

PubMed

Perharič, Lucija; Fatur, Tanja; Drofenik, Jernej

2016-06-01

In view of the European Union regulations 1107/2009 and 528/2012, which say that basic substances in plant protection and biocidal products marketed in the European Union (EU) should not have an inherent capacity to cause endocrine disruption, an initiative was started to define scientific criteria for the identification of endocrine disruptors (EDs). The objectives of the EU strategy on EDs are to protect human health and the environment, to assure the functioning of the market, and to provide clear and coherent criteria for the identification of EDs that could have broad application in the EU legislation. Policy issues were to be addressed by the Ad-hoc group of Commission Services, EU Agencies and Member States established in 2010, whereas the scientific issues were to be addressed by the Endocrine Disruptors Expert Advisory Group (ED EAG), established in 2011. The ED EAG adopted the 2002 World Health Organization (WHO) definition of endocrine disruptor and agreed that for its identification it is necessary to produce convincing evidence of a biologically plausible causal link between an adverse effect and endocrine disrupting mode of action. In 2014, the European Commission proposed four ED identification criteria options and three regulatory options, which are now being assessed for socio-economic, environmental, and health impact. Slovenia supports the establishing of identification criteria and favours option 4, according to which ED identification should be based on the WHO definition with the addition of potency as an element of hazard characterisation. As for regulatory options, Slovenia favours the risk-based rather than hazard-based regulation.

Chronology of endocrine differentiation and beta-cell neogenesis.

PubMed

Miyatsuka, Takeshi

2016-01-01

Diabetes is a chronic and incurable disease, which results from absolute or relative insulin insufficiency. Therefore, pancreatic beta cells, which are the only type of cell that expresses insulin, is considered to be a potential target for the cure of diabetes. Although the findings regarding beta-cell neogenesis during pancreas development have been exploited to induce insulin-producing cells from non-beta cells, there are still many hurdles towards generating fully functional beta cells that can produce high levels of insulin and respond to physiological signals. To overcome these problems, a solid understanding of pancreas development and beta-cell formation is required, and several mouse models have been developed to reveal the unique features of each endocrine cell type at distinct developmental time points. Here I review our understanding of pancreas development and endocrine differentiation focusing on recent progresses in improving temporal cell labeling in vivo.

Minireview: Endocrine Disruptors: Past Lessons and Future Directions

PubMed Central

Johnson, Anne F.; Birnbaum, Linda S.; Colborn, Theo; Guillette, Louis J.; Crews, David P.; Collins, Terry; Soto, Ana M.; vom Saal, Frederick S.; McLachlan, John A.; Sonnenschein, Carlos; Heindel, Jerrold J.

2016-01-01

Within the past few decades, the concept of endocrine-disrupting chemicals (EDCs) has risen from a position of total obscurity to become a focus of dialogue, debate, and concern among scientists, physicians, regulators, and the public. The emergence and development of this field of study has not always followed a smooth path, and researchers continue to wrestle with questions about the low-dose effects and nonmonotonic dose responses seen with EDCs, their biological mechanisms of action, the true pervasiveness of these chemicals in our environment and in our bodies, and the extent of their effects on human and wildlife health. This review chronicles the development of the unique, multidisciplinary field of endocrine disruption, highlighting what we have learned about the threat of EDCs and lessons that could be relevant to other fields. It also offers perspectives on the future of the field and opportunities to better protect human health. PMID:27477640

Discovery of naturally occurring ESR1 mutations in breast cancer cell lines modelling endocrine resistance.

PubMed

Martin, Lesley-Ann; Ribas, Ricardo; Simigdala, Nikiana; Schuster, Eugene; Pancholi, Sunil; Tenev, Tencho; Gellert, Pascal; Buluwela, Laki; Harrod, Alison; Thornhill, Allan; Nikitorowicz-Buniak, Joanna; Bhamra, Amandeep; Turgeon, Marc-Olivier; Poulogiannis, George; Gao, Qiong; Martins, Vera; Hills, Margaret; Garcia-Murillas, Isaac; Fribbens, Charlotte; Patani, Neill; Li, Zheqi; Sikora, Matthew J; Turner, Nicholas; Zwart, Wilbert; Oesterreich, Steffi; Carroll, Jason; Ali, Simak; Dowsett, Mitch

2017-11-30

Resistance to endocrine therapy remains a major clinical problem in breast cancer. Genetic studies highlight the potential role of estrogen receptor-α (ESR1) mutations, which show increased prevalence in the metastatic, endocrine-resistant setting. No naturally occurring ESR1 mutations have been reported in in vitro models of BC either before or after the acquisition of endocrine resistance making functional consequences difficult to study. We report the first discovery of naturally occurring ESR1 Y537C and ESR1 Y537S mutations in MCF7 and SUM44 ESR1-positive cell lines after acquisition of resistance to long-term-estrogen-deprivation (LTED) and subsequent resistance to fulvestrant (ICIR). Mutations were enriched with time, impacted on ESR1 binding to the genome and altered the ESR1 interactome. The results highlight the importance and functional consequence of these mutations and provide an important resource for studying endocrine resistance.

Endocrine radionuclide scintigraphy with fusion single photon emission computed tomography/computed tomography

PubMed Central

Wong, Ka-Kit; Gandhi, Arpit; Viglianti, Benjamin L; Fig, Lorraine M; Rubello, Domenico; Gross, Milton D

2016-01-01

AIM: To review the benefits of single photon emission computed tomography (SPECT)/computed tomography (CT) hybrid imaging for diagnosis of various endocrine disorders. METHODS: We performed MEDLINE and PubMed searches using the terms: “SPECT/CT”; “functional anatomic mapping”; “transmission emission tomography”; “parathyroid adenoma”; “thyroid cancer”; “neuroendocrine tumor”; “adrenal”; “pheochromocytoma”; “paraganglioma”; in order to identify relevant articles published in English during the years 2003 to 2015. Reference lists from the articles were reviewed to identify additional pertinent articles. Retrieved manuscripts (case reports, reviews, meta-analyses and abstracts) concerning the application of SPECT/CT to endocrine imaging were analyzed to provide a descriptive synthesis of the utility of this technology. RESULTS: The emergence of hybrid SPECT/CT camera technology now allows simultaneous acquisition of combined multi-modality imaging, with seamless fusion of three-dimensional volume datasets. The usefulness of combining functional information to depict the bio-distribution of radiotracers that map cellular processes of the endocrine system and tumors of endocrine origin, with anatomy derived from CT, has improved the diagnostic capability of scintigraphy for a range of disorders of endocrine gland function. The literature describes benefits of SPECT/CT for 99mTc-sestamibi parathyroid scintigraphy and 99mTc-pertechnetate thyroid scintigraphy, 123I- or 131I-radioiodine for staging of differentiated thyroid carcinoma, 111In- and 99mTc- labeled somatostatin receptor analogues for detection of neuroendocrine tumors, 131I-norcholesterol (NP-59) scans for assessment of adrenal cortical hyperfunction, and 123I- or 131I-metaiodobenzylguanidine imaging for evaluation of pheochromocytoma and paraganglioma. CONCLUSION: SPECT/CT exploits the synergism between the functional information from radiopharmaceutical imaging and anatomy

Problem-based learning within endocrine physiology lectures.

PubMed

Walters, M R

2001-12-01

Methods were needed to improve the interest of medical students in the 10-lecture Endocrine Physiology block at the end of the second semester of study. Other incentives for improvement included the possibility of attracting students into endocrine research electives and the pressure to improve teaching approaches that results from the high tuition they pay. The principal approach adopted was that of whole class problem-based learning sessions (PBLS) in which the lecture period begins with a brief overview of one to three simplified cases, followed by the usual didactic lecture. At the end of the lecture, each PBL case is read in detail, with several questions posed to the students. Their answers are then used to reinforce concepts from the lecture material. This method can also provide some continuity between lectures, either by using a case in several lectures to illustrate different points, or by posing a question at the beginning of class that illustrates a point from the prior lecture. The outcome of this approach has been very successful: student evaluations of the lecture block and their attendance have significantly improved.

Multiple endocrine neoplasia syndrome type 1: institution, management, and data analysis of a nationwide multicenter patient database.

PubMed

Giusti, Francesca; Cianferotti, Luisella; Boaretto, Francesca; Cetani, Filomena; Cioppi, Federica; Colao, Annamaria; Davì, Maria Vittoria; Faggiano, Antongiulio; Fanciulli, Giuseppe; Ferolla, Piero; Ferone, Diego; Fossi, Caterina; Giudici, Francesco; Gronchi, Giorgio; Loli, Paola; Mantero, Franco; Marcocci, Claudio; Marini, Francesca; Masi, Laura; Opocher, Giuseppe; Beck-Peccoz, Paolo; Persani, Luca; Scillitani, Alfredo; Sciortino, Giovanna; Spada, Anna; Tomassetti, Paola; Tonelli, Francesco; Brandi, Maria Luisa

2017-11-01

The aim of this study was to integrate European epidemiological data on patients with multiple endocrine neoplasia type 1 by creating an Italian registry of this syndrome, including clinical and genetic characteristics and therapeutic management. Clinical, familial and genetic data of patients with multiple endocrine neoplasia type 1, diagnosed, treated, and followed-up for a mean time of 11.3 years, in 14 Italian referral endocrinological centers, were collected, over a 3-year course (2011-2013), to build a national electronic database. The Italian multiple endocrine neoplasia type 1 database includes 475 patients (271 women and 204 men), of whom 383 patients (80.6%) were classified as familial cases (from 136 different pedigrees), and 92 (19.4%) patients were sporadic cases. A MEN1 mutation was identified in 92.6% of familial cases and in 48.9% of sporadic cases. Four hundred thirty-six patients were symptomatic, presenting primary hyperparathyroidism, gastroenteropancreatic neuroendocrine tumors and pituitary tumors in 93, 53, and 41% of cases, respectively. Thirty-nine subjects, belonging to affected pedigrees positive for a MEN1 mutation, were asymptomatic at clinical and biochemical screening. Age at diagnosis of multiple endocrine neoplasia type 1 probands was similar for both familial and simplex cases (mean age 47.2 ± 15.3 years). In familial cases, diagnosis of multiple endocrine neoplasia type 1 in relatives of affected probands was made more than 10 years in advance (mean age at diagnosis 36.5 ± 17.6 years). The analysis of Italian registry of multiple endocrine neoplasia type 1 patients revealed that clinical features of Italian multiple endocrine neoplasia type 1 patients are similar to those of other western countries, and confirmed that the genetic test allowed multiple endocrine neoplasia type 1 diagnosis 10 years earlier than biochemical or clinical diagnosis.

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.

Minireview: Gut Microbiota: The Neglected Endocrine Organ

PubMed Central

Clarke, Gerard; Stilling, Roman M.; Kennedy, Paul J.; Stanton, Catherine; Cryan, John F.

2014-01-01

The concept that the gut microbiota serves as a virtual endocrine organ arises from a number of important observations. Evidence for a direct role arises from its metabolic capacity to produce and regulate multiple compounds that reach the circulation and act to influence the function of distal organs and systems. For example, metabolism of carbohydrates results in the production of short-chain fatty acids, such as butyrate and propionate, which provide an important source of nutrients as well as regulatory control of the host digestive system. This influence over host metabolism is also seen in the ability of the prebiotic inulin to influence production of relevant hormones such as glucagon-like peptide-1, peptide YY, ghrelin, and leptin. Moreover, the probiotic Lactobacillus rhamnosus PL60, which produces conjugated linoleic acid, has been shown to reduce body-weight gain and white adipose tissue without effects on food intake. Manipulating the microbial composition of the gastrointestinal tract modulates plasma concentrations of tryptophan, an essential amino acid and precursor to serotonin, a key neurotransmitter within both the enteric and central nervous systems. Indirectly and through as yet unknown mechanisms, the gut microbiota exerts control over the hypothalamic-pituitary-adrenal axis. This is clear from studies on animals raised in a germ-free environment, who show exaggerated responses to psychological stress, which normalizes after monocolonization by certain bacterial species including Bifidobacterium infantis. It is tempting to speculate that therapeutic targeting of the gut microbiota may be useful in treating stress-related disorders and metabolic diseases. PMID:24892638

Drug residues and endocrine disruptors in drinking water: risk for humans?

PubMed

Touraud, Evelyne; Roig, Benoit; Sumpter, John P; Coetsier, Clémence

2011-11-01

The presence of pharmaceuticals and endocrine disruptors in the environment raises many questions about risk to the environment and human health. Environmental exposure has been largely studied, providing to date a realistic picture of the degree of contamination of the environment by pharmaceuticals and hormones. Conversely, little information is available regarding human exposure. NSAIDS, carbamazepine, iodinated contrast media, β-blockers, antibiotics have been detected in drinking water, mostly in the range of ng/L. it is questioned if such concentrations may affect human health. Currently, no consensus among the scientific community exists on what risk, if any, pharmaceuticals and endocrine disruptors pose to human health. Future European research will focus, on one hand, on genotoxic and cytotoxic anti-cancer drugs and, on the other hand, on the induction of genetic resistance by antibiotics. This review does not aim to give a comprehensive overview of human health risk of drug residues and endocrine disruptors in drinking water but rather highlight important topics of discussion. Copyright © 2011. Published by Elsevier GmbH.

Analysis of endocrine activity in drinking water, surface water and treated wastewater from six countries.

PubMed

Leusch, Frederic D L; Neale, Peta A; Arnal, Charlotte; Aneck-Hahn, Natalie H; Balaguer, Patrick; Bruchet, Auguste; Escher, Beate I; Esperanza, Mar; Grimaldi, Marina; Leroy, Gaela; Scheurer, Marco; Schlichting, Rita; Schriks, Merijn; Hebert, Armelle

2018-08-01

The aquatic environment can contain numerous micropollutants and there are concerns about endocrine activity in environmental waters and the potential impacts on human and ecosystem health. In this study a complementary chemical analysis and in vitro bioassay approach was applied to evaluate endocrine activity in treated wastewater, surface water and drinking water samples from six countries (Germany, Australia, France, South Africa, the Netherlands and Spain). The bioassay test battery included assays indicative of seven endocrine pathways, while 58 different chemicals, including pesticides, pharmaceuticals and industrial compounds, were analysed by targeted chemical analysis. Endocrine activity was below the limit of quantification for most water samples, with only two of six treated wastewater samples and two of six surface water samples exhibiting estrogenic, glucocorticoid, progestagenic and/or anti-mineralocorticoid activity above the limit of quantification. Based on available effect-based trigger values (EBT) for estrogenic and glucocorticoid activity, some of the wastewater and surface water samples were found to exceed the EBT, suggesting these environmental waters may pose a potential risk to ecosystem health. In contrast, the lack of bioassay activity and low detected chemical concentrations in the drinking water samples do not suggest a risk to human endocrine health, with all samples below the relevant EBTs. Copyright © 2018 Elsevier Ltd. All rights reserved.

Endocrine Disruptor Screening Program: Tier I Screening Battery

EPA Science Inventory

In response to emerging concerns that environmental chemicals may have adverse effects on human health by altering the function of the endocrine system,' the Food Quality Protection Act and subsequent amendments to the Safe Drinking Water Act and Federal Food, Drug and Cosmetic A...

Preliminary study of the role of gastrointestinal endocrine cells in the maintenance of villous structure following X-irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wyatt, M.G.; Hume, S.P.; Carr, K.E.

The mechanism of gastrointestinal villous damage following ionizing irradiation is complex. Various compartments within the gastrointestinal tract have in turn been considered important for the maintenance of normal villous structure. To date, however, evidence for a single overriding regulator of epithelial well-being is lacking. In this study, the role of the gastro-intestinal (enteroendocrine) cells is explored and comparison made between endocrine cell number and villous structure. Experiments were organized using both control and irradiated groups of mice. Two time points (1 and 3 days) and three radiation doses (6, 10 and 18Gy) were employed. A simple method for endocrine cellmore » identification and subsequent quantification is described. Endocrine cell number was then compared with villous surface detail, as seen with a scanning electron microscope (SEM). Results indicated a decrease in the endocrine cell number at all three radiation doses. Whereas at low doses endocrine cell recovery occurred between 1 and 3 days, at medium and high doses further decline was noticed. A similar pattern was seen when considering villous surface structure. It is suggested that both scanning electron microscopy and endocrine cell number provide a more sensitive indicator of gastrointestinal radiation damage than do current crypt counting techniques. In addition, a link between endocrine cell number and villous structure is proposed.« less

Avian endocrine responses to environmental pollutants

USGS Publications Warehouse

Rattner, B.A.; Eroschenko, V.P.; Fox, G.A.; Fry, D.M.; Gorsline, J.

1984-01-01

Many environmental contaminants are hazardous to populations of wild birds. Chlorinated hydrocarbon pesticides and industrial pollutants are thought to be responsible for population declines of several species of predatory birds through eggshell thinning. Studies have demonstrated that these contaminants have estrogenic potency and may affect the functioning of the gonadal and thyroidal endocrine subsystems. Petroleum crude oil exerts toxicity externally, by oiling of plumage, and internally, by way of ingestion of oil while feeding or preening. Extensive ultrastructural damage to the inner zone of the adrenal, diminished adrenal responsiveness to adrenocorticotrophic hormone, and reduced corticosterone secretion rate suggest that low levels of plasma corticosterone reflect a direct effect of petroleum on the adrenal gland. Suppressive effects of oil on the ovary and decreases in circulating prolactin have been associated with impaired reproductive function. Large-scale field studies of free-living seabirds have confirmed some of the inhibitory effects of oil on reproduction that have been observed in laboratory studies. Organophosphorus insecticides, representing the most widely used class of pesticides in North America, have been shown to impair reproductive function, possibly by altering secretion of luteinizing hormone and progesterone. Relevant areas of future research on the effects of contaminants on avian endocrine function are discussed.

β-Cell-Specific Mafk Overexpression Impairs Pancreatic Endocrine Cell Development

PubMed Central

Abdellatif, Ahmed M.; Oishi, Hisashi; Itagaki, Takahiro; Jung, Yunshin; Shawki, Hossam H.; Okita, Yukari; Hasegawa, Yoshikazu; Suzuki, Hiroyuki; El-Morsy, Salah E.; El-Sayed, Mesbah A.; Shoaib, Mahmoud B.; Sugiyama, Fumihiro; Takahashi, Satoru

2016-01-01

The MAF family transcription factors are homologs of v-Maf, the oncogenic component of the avian retrovirus AS42. They are subdivided into 2 groups, small and large MAF proteins, according to their structure, function, and molecular size. MAFK is a member of the small MAF family and acts as a dominant negative form of large MAFs. In previous research we generated transgenic mice that overexpress MAFK in order to suppress the function of large MAF proteins in pancreatic β-cells. These mice developed hyperglycemia in adulthood due to impairment of glucose-stimulated insulin secretion. The aim of the current study is to examine the effects of β-cell-specific Mafk overexpression in endocrine cell development. The developing islets of Mafk-transgenic embryos appeared to be disorganized with an inversion of total numbers of insulin+ and glucagon+ cells due to reduced β-cell proliferation. Gene expression analysis by quantitative RT-PCR revealed decreased levels of β-cell-related genes whose expressions are known to be controlled by large MAF proteins. Additionally, these changes were accompanied with a significant increase in key β-cell transcription factors likely due to compensatory mechanisms that might have been activated in response to the β-cell loss. Finally, microarray comparison of gene expression profiles between wild-type and transgenic pancreata revealed alteration of some uncharacterized genes including Pcbd1, Fam132a, Cryba2, and Npy, which might play important roles during pancreatic endocrine development. Taken together, these results suggest that Mafk overexpression impairs endocrine development through a regulation of numerous β-cell-related genes. The microarray analysis provided a unique data set of differentially expressed genes that might contribute to a better understanding of the molecular basis that governs the development and function of endocrine pancreas. PMID:26901059

Conserved Genetic Pathways Controlling the Development of the Diffuse Endocrine System in Vertebrates and Drosophila

PubMed Central

Hartenstein, Volker; Takashima, Shigeo; Adams, Katrina

2014-01-01

The midgut epithelium is formed by absorptive enterocytes, secretory cells and endocrine cells. Each of these lineages is derived from the pluripotent progenitors that constitute the embryonic endoderm; the mature midgut retains pools of self-renewing stem cells that continue to produce all lineages. Recent findings in vertebrates and Drosophila shed light on the genetic mechanism that specifies the fate of the different lineages. A pivotal role is played by the Notch signaling pathway that, in a manner that appears to be very similar to the way in which Notch signaling selects neural progenitors within the neurectoderm, distinguishes the fate of secretory/endocrine cells and enterocytes. Proneural genes encoding bHLH transcription factors are expressed and required in prospective endocrine cells; activation of the Notch pathways restricts the number of these cells and promotes enterocyte development. In this review we compare the development of the intestinal endocrine cells in vertebrates and insects and summarize recent findings dealing with genetic pathways controlling this cell type. PMID:20005229

Möhnite, (NH4)K2Na(SO4)2, a new guano mineral from Pabellón de Pica, Chile

NASA Astrophysics Data System (ADS)

Chukanov, Nikita V.; Aksenov, Sergey M.; Rastsvetaeva, Ramiza K.; Pekov, Igor V.; Belakovskiy, Dmitry I.; Britvin, Sergey N.

2015-10-01

The new mineral möhnite, ideally (NH4)K2Na(SO4)2, the ammonium analogue of aphthitalite, is found in a guano deposit on the Pabellón de Pica mountain, near Chanabaya, Iquique Province, Tarapacá Region, Chile. It is associated with salammoniac, halite, joanneumite, natroxalate, nitratine, chanabayaite, and a clay mineral. Möhnite occurs as random aggregates and clusters of brown imperfect bipyramidal or spindle-shaped crystals. The mineral is brittle, with Mohs' hardness of 3; Dmeas is 2.4(1) g/cm3 and Dcalc is 2.461 g/cm3. The IR spectrum shows the presence of NH4 + cations (the bands at 1431, 3076 and 3240 cm-1). Möhnite is almost isotropic, optically neutral; ɛ = ω = 1.505(2). The chemical composition (electron-microprobe data, N determined by gas chromatography of products of ignition, H calculated by stoichiometry, wt%) is: (NH4)2O 7.99, Na2O 9.49, K2O 32.34, SO3 51.32, total 101.14. The empirical formula is (NH4)0.95Na0.95 K2.14S1.99O8. The crystal structure was solved and refined to R = 0.049 based on 241 unique reflections with I > 2σ( I). Möhnite is trigonal, space group P m1, a = 5.7402(3) Å, c = 7.435(1) Å, V = 212.16(4) Å3, Z = 1. The strongest reflections of the powder X-ray diffraction pattern [ d, Å ( I,%) ( hkl)] are: 4.955 (27) (100), 4.122 (37) (101, 011), 3.708 (29) (002), 2.969 (74) (102, 012), 2.861 (100) (110), 2.474 (20) (003), 2.060 (33) (022). The mineral is named in honour of the German amateur mineralogist Gerhard Möhn (born 1959).

[Chronic heart failure and cachexia: role of endocrine system].

PubMed

Dei Cas, A; Muoio, A; Zavaroni, I

2011-12-01

Chronic heart failure (CHF) is a major health problem that carries a devastating prognosis. The prognosis worsens considerably once cardiac cachexia has been diagnosed. Neurohormonal, metabolic, hemodynamic and immunological alterations are involved in the initiation and progression of cardiac cachexia. Cachexia is characterized by a hypothalamic inappropriate response to the mechanisms controlling energy homeostasis. Levels of the anorexigenic hormone leptin are decreased whereas the orexigenic gherlin hormone levels are normal or elevated. Nevertheless, energy intake is not increased as expected due to a persistent activation of the proopiomelanocortin (POMC) system (anorexigenic) paralleled by a decreased activity of the neuropeptide Y (NPY, orexigenic) neurons. Cachexia is also characterized by an imbalance in anabolic (impairment in the growth hormone/insulin-like growth factor-I axis, insulin resistance) and catabolic (increased levels of catecholamines, increased cortisol/dehydroepiandrosterone ratio and activation of proinflammatory cytokines such as tumor necrosis factor-alpha, interleuchin-6, interleuchin-1') at the basis of the wasting process. This review discusses the complex role of the endocrine system in modulating energy balance, appetite and metabolism in patients with chronic heart failure. A joint multidisciplinary effort of the cardiologists, immunologists and endocrinologists might be useful to identify the precise mechanisms involved in the neuroendocrine alteration and to develop therapeutic strategies able to improve the prognosis of CHF patients.

Endocrine disrupting chemicals in the atmosphere: Their effects on humans and wildlife.

PubMed

Annamalai, Jayshree; Namasivayam, Vasudevan

2015-03-01

Endocrine disrupting chemicals (EDCs) are exogenous agents that interfere or disrupt the normal synthesis, secretion, transportation, binding and metabolism of natural hormones; eventually dysregulating homeostatic mechanisms, reproduction and development. They are emitted into the atmosphere during anthropogenic activities and physicochemical reactions in nature. Inhalation of these EDCs as particulate and gaseous vapors triggers their interaction with endocrine glands and exerts agonist or antagonists actions at hormone receptors. The endocrine disruption at nanogram levels of EDC's has gained concern in the last decade, due to infertility among men and women, early puberty, obesity, diabetes and cancer. Thus, the review explores the literature that addresses the major occurring EDCs in the atmosphere including phthalates, polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), brominated flame retardants (BFRs), dioxins, alkylphenols (APs) and perfluorinated chemicals (PFCs). Sources, fate, half-life, mechanism, measured concentrations in air, bioaccumulation in tissues, laboratory exposures correlating to toxicological effects of these EDCs in humans and wildlife are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Long term effects of extended adjuvant endocrine therapy on quality of life in breast cancer patients.

PubMed

Kool, M; Fontein, D B Y; Meershoek-Klein Kranenbarg, E; Nortier, J W R; Rutgers, E J T; Marang-van de Mheen, P J; van de Velde, C J H

2015-06-01

The standard treatment for hormone-receptor positive, postmenopausal early breast cancer patients is 5 years of adjuvant endocrine therapy. Previous studies demonstrate that prolonging adjuvant endocrine therapy may improve disease-free survival. However, endocrine therapy is known for its adverse events, which may negatively affect Quality of Life (QoL). The aim of this study is to assess the impact of extended adjuvant endocrine therapy on long-term QoL outcomes. 471 patients selected from the IDEAL trial were invited to complete a questionnaire 1-1.5 years after starting with extended therapy. The questionnaire consisted of the EORTC QLQ-C30 and QLQ-BR23 questionnaires. Mean QoL outcomes were compared with EORTC reference values for stage I and II breast cancer patients and the general population. Furthermore, QoL outcomes were compared between different treatment regimens. A difference of eight points was considered clinically relevant. IDEAL patients receiving extended adjuvant endocrine therapy have significantly and clinically relevant better global QoL compared with reference values for stage I and II breast cancer patients (79.6 versus 64.6; p < 0.01) and the general population (79.6 versus 71.2; p < 0.01). Similar results were found for emotional function, pain, appetite loss, diarrhea and financial problems. Between treatment regimens prior to extended adjuvant endocrine therapy, differences were only found on specific QoL domains (e.g. arm symptoms). Breast cancer patients on extended adjuvant endocrine therapy have significantly and clinically relevant better global QoL compared with other stage I-II breast cancer patients and the general population, 6-8.5 years after diagnosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

The effect of a dedicated endocrine surgery program on general surgery training: a single institutional experience.

PubMed

Wiseman, James E; Ituarte, Philip H G; Ro, Kevin; Pasternak, Jesse D; Quach, Chi A; Tillou, Areti K; Hines, O Joe; Hiatt, Jonathan R; Yeh, Michael W

2012-06-01

The endocrine surgery program was established at the University of California, Los Angeles, in 2006 to enhance the educational experience of surgical residents in this area. The impact of this program on subjective and objective measures of resident education was prospectively tracked. Resident case logs, American Board of Surgery In-Training Examination scores, self-assessment surveys, and annual rotation evaluations from July 2005 to June 2009 were reviewed. The mean number of endocrine cases reported by graduates doubled during the study period (from 18 to 36, P < .001). Self-assessment scores increased for thyroid (from 4.53 to 5.76, P = .04) and parathyroid (from 4.46 to 5.90, P = .03) disorders. The mean rating for the endocrine rotation (from 3.23 to 3.95, P = .005) improved, with specific increases in the quantity (from 3.05 to 3.74, P = .02) and quality (from 3.25 to 3.95, P = .002) of operative experience. Since 2006, trainees have coauthored 17 peer-reviewed reports and 3 textbook chapters on endocrine topics. The establishment of a dedicated endocrine surgery program has a measurable impact on resident education within this core content area. Copyright © 2012. Published by Elsevier Inc.

Removal of Group B Streptococci Colonizing the Vagina and Oropharynx of Mice with a Bacteriophage Lytic Enzyme

PubMed Central

Cheng, Qi; Nelson, Daniel; Zhu, Shiwei; Fischetti, Vincent A.

2005-01-01

Group B streptococci (GBS) are the leading cause of neonatal meningitis and sepsis worldwide. The current treatment strategy is limited to intrapartum antibiotic prophylaxis in pregnant women to prevent early-onset neonatal diseases, but considering the potential for antibiotic resistance, the risk of losing control over the disease is high. To approach this problem, we have developed a bacteriophage (phage) lytic enzyme to remove colonizing GBS. Bacteriophage muralytic enzymes, termed lysins, are highly evolved molecules designed to degrade the cell wall of host bacteria to release phage particles from the bacterial cytoplasm. Several different lysins have been developed to specifically kill bacterial pathogens both on mucosal surfaces and in blood and represent a novel approach to control infection. A lysin cloned from a phage infecting GBS was found to contain two putative catalytic domains and one putative binding domain, which is similar to the domain organization of some staphylococcal phage lysins. The lysin (named PlyGBS) was recombinantly expressed in Escherichia coli, and purified PlyGBS efficiently killed all tested GBS serotypes in vitro. In a mouse model, a single dose of PlyGBS significantly reduced bacterial colonization in both the vagina and oropharynx. As an alternative strategy for intrapartum antibiotic prophylaxis, this approach may be used to reduce vaginal GBS colonization in pregnant women before delivery or to decontaminate newborns, thus reducing the incidence of GBS-associated neonatal meningitis and sepsis. PMID:15616283

Navigation through inter- and intratumoral heterogeneity of endocrine resistance mechanisms in breast cancer: A potential role for Liquid Biopsies?

PubMed

Reinhardt, Florian; Franken, André; Fehm, Tanja; Neubauer, Hans

2017-11-01

The majority of breast cancers are hormone receptor positive due to the expression of the estrogen and/or progesterone receptors. Endocrine therapy is a major treatment option for all disease stages of hormone receptor-positive breast cancer and improves overall survival. However, endocrine therapy is limited by de novo and acquired resistance. Several factors have been proposed for endocrine therapy failures, which include molecular alterations in the estrogen receptor pathway, altered expression of cell-cycle regulators, autophagy, and epithelial-to-mesenchymal transition as a consequence of tumor progression and selection pressure. It is essential to reveal and monitor intra- and intertumoral alterations in breast cancer to allow optimal therapy outcome. Endocrine therapy navigation by molecular profiling of tissue biopsies is the current gold standard but limited in many reasons. "Liquid biopsies" such as circulating-tumor cells and circulating-tumor DNA offer hope to fill that gap in allowing non-invasive serial assessment of biomarkers predicting success of endocrine therapy regimen. In this context, this review will provide an overview on inter- and intratumoral heterogeneity of endocrine resistance mechanisms and discuss the potential role of "liquid biopsies" as navigators to personalize treatment methods and prevent endocrine treatment resistance in breast cancer.

Abnormal endocrine pancreas function at birth in cystic fibrosis ferrets

PubMed Central

Olivier, Alicia K.; Yi, Yaling; Sun, Xingshen; Sui, Hongshu; Liang, Bo; Hu, Shanming; Xie, Weiliang; Fisher, John T.; Keiser, Nicholas W.; Lei, Diana; Zhou, Weihong; Yan, Ziying; Li, Guiying; Evans, Turan I.A.; Meyerholz, David K.; Wang, Kai; Stewart, Zoe A.; Norris, Andrew W.; Engelhardt, John F.

2012-01-01

Diabetes is a common comorbidity in cystic fibrosis (CF) that worsens prognosis. The lack of an animal model for CF-related diabetes (CFRD) has made it difficult to dissect how the onset of pancreatic pathology influences the emergence of CFRD. We evaluated the structure and function of the neonatal CF endocrine pancreas using a new CFTR-knockout ferret model. Although CF kits are born with only mild exocrine pancreas disease, progressive exocrine and endocrine pancreatic loss during the first months of life was associated with pancreatic inflammation, spontaneous hyperglycemia, and glucose intolerance. Interestingly, prior to major exocrine pancreas disease, CF kits demonstrated significant abnormalities in blood glucose and insulin regulation, including diminished first-phase and accentuated peak insulin secretion in response to glucose, elevated peak glucose levels following glucose challenge, and variably elevated insulin and C-peptide levels in the nonfasted state. Although there was no difference in lobular insulin and glucagon expression between genotypes at birth, significant alterations in the frequencies of small and large islets were observed. Newborn cultured CF islets demonstrated dysregulated glucose-dependent insulin secretion in comparison to controls, suggesting intrinsic abnormalities in CF islets. These findings demonstrate that early abnormalities exist in the regulation of insulin secretion by the CF endocrine pancreas. PMID:22996690

ESR1 mutations as a mechanism for acquired endocrine resistance in breast cancer

PubMed Central

Jeselsohn, Rinath; Buchwalter, Gilles; De Angelis, Carmine; Brown, Myles; Schiff, Rachel

2016-01-01

Most breast cancers are estrogen receptor α (ER)-positive (+) and are treated with endocrine therapies targeting ER activity. Despite efforts, the mechanisms of the frequent clinical resistance to these therapies remain largely unknown. Several recent parallel studies unveiled gain-of-function recurrent ESR1 mutations in up to 20% of patients with metastatic ER+ disease who all received endocrine therapies, which for more cases included an aromatase inhibitor. These mutations, clustered in a hotspot within the ligand-binding domain (LBD), lead to ligand independent ER activity and tumor growth, partial resistance to tamoxifen and fulvestrant, and potentially increased metastatic capacity. Together, these findings suggest that the ESR1 LBD mutations account for acquired endocrine resistance in a substantial fraction of patients with metastatic disease. The absence of detectable ESR1 mutations in treatment-naïve disease and the correlation with the number of endocrine treatments indicate a clonal expansion of rare mutant clones, selected under the pressure of treatment. New technologies to detect low/ultra rare ESR1 mutations together with tissue and liquid biopsies are required to fully expose their clinical relevance in prognosis and treatment. Pre-clinical and clinical development of rationale-based novel therapeutic strategies to inhibit these mutants has the potential to substantially improve treatment outcomes. PMID:26122181

In Vitro Effects of the Endocrine Disruptor p,p’-DDT on Human Follitropin Receptor

PubMed Central

Munier, Mathilde; Grouleff, Julie; Gourdin, Louis; Fauchard, Mathilde; Chantreau, Vanessa; Henrion, Daniel; Coutant, Régis; Schiøtt, Birgit; Chabbert, Marie; Rodien, Patrice

2016-01-01

Background: 1-chloro-4-[2,2,2-trichloro-1-(4-chlorophenyl)ethyl]benzene (p,p′-DDT) is a persistent environmental endocrine disruptor (ED). Several studies have shown an association between p,p′-DDT exposure and reproductive abnormalities. Objectives: To investigate the putative effects of p,p′-DDT on the human follitropin receptor (FSHR) function. Methods and Results: We used Chinese hamster ovary (CHO) cells stably expressing human FSHR to investigate the impact of p,p′-DDT on FSHR activity and its interaction with the receptor. At a concentration of 5 μM p,p′-DDT increased the maximum response of the FSHR to follitropin by 32 ± 7.45%. However, 5 μM p,p′-DDT decreased the basal activity and did not influence the maximal response of the closely related LH/hCG receptor to human chorionic gonadotropin (hCG). The potentiating effect of p,p′-DDT was specific for the FSHR. Moreover, in cells that did not express FSHR, p,p′-DDT had no effect on cAMP response. Thus, the potentiating effect of p,p′-DDT was dependent on the FSHR. In addition, p,p′-DDT increased the sensitivity of FSHR to hCG and to a low molecular weight agonist of the FSHR, 3-((5methyl)-2-(4-benzyloxy-phenyl)-5-{[2-[3-ethoxy-4-methoxy-phenyl)-ethylcarbamoyl]-methyl}-4-oxo-thiazolidin-3-yl)-benzamide (16a). Basal activity in response to p,p′-DDT and potentiation of the FSHR response to FSH by p,p′-DDT varied among FSHR mutants with altered transmembrane domains (TMDs), consistent with an effect of p,p′-DDT via TMD binding. This finding was corroborated by the results of simultaneously docking p,p′-DDT and 16a into the FSHR transmembrane bundle. Conclusion: p,p′-DDT acted as a positive allosteric modulator of the FSHR in our experimental model. These findings suggest that G protein–coupled receptors are additional targets of endocrine disruptors. Citation: Munier M, Grouleff J, Gourdin L, Fauchard M, Chantreau V, Henrion D, Coutant R, Schiøtt B, Chabbert M, Rodien P. 2016

The development and endocrine functions of adipose tissue

USDA-ARS?s Scientific Manuscript database

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...

Prevalence of endocrine and genetic abnormalities in boys evaluated systematically for a disorder of sex development.

PubMed

Nixon, R; Cerqueira, V; Kyriakou, A; Lucas-Herald, A; McNeilly, J; McMillan, M; Purvis, A I; Tobias, E S; McGowan, R; Ahmed, S F

2017-10-01

What is the likelihood of identifying genetic or endocrine abnormalities in a group of boys with 46, XY who present to a specialist clinic with a suspected disorder of sex development (DSD)? An endocrine abnormality of the gonadal axis may be present in a quarter of cases and copy number variants (CNVs) or single gene variants may be present in about half of the cases. Evaluation of 46, XY DSD requires a combination of endocrine and genetic tests but the prevalence of these abnormalities in a sufficiently large group of boys presenting to one specialist multidisciplinary service is unclear. This study was a retrospective review of investigations performed on 122 boys. All boys who attended the Glasgow DSD clinic, between 2010 and 2015 were included in the study. The median external masculinization score (EMS) of this group was 9 (range 1-11). Details of phenotype, endocrine and genetic investigations were obtained from case records. An endocrine abnormality of gonadal function was present in 28 (23%) with a median EMS of 8.3 (1-10.5) whilst the median EMS of boys with normal endocrine investigations was 9 (1.5-11) (P = 0.03). Endocrine abnormalities included a disorder of gonadal development in 19 (16%), LH deficiency in 5 (4%) and a disorder of androgen synthesis in 4 (3%) boys. Of 43 cases who had array-comparative genomic hybridization (array-CGH), CNVs were reported in 13 (30%) with a median EMS of 8.5 (1.5-11). Candidate gene analysis using a limited seven-gene panel in 64 boys identified variants in 9 (14%) with a median EMS of 8 (1-9). Of the 21 boys with a genetic abnormality, 11 (52%) had normal endocrine investigations. A selection bias for performing array-CGH in cases with multiple congenital malformations may have led to a high yield of CNVs. It is also possible that the yield of single gene variants may have been higher than reported if the investigators had used a more extended gene panel. The lack of a clear association between the extent of under

Intranasal sedation using ketamine and midazolam for pediatric dental treatment (NASO): study protocol for a randomized controlled trial.

PubMed

Gomes, Heloisa Sousa; Miranda, Analya Rodrigues; Viana, Karolline Alves; Batista, Aline Carvalho; Costa, Paulo Sucasas; Daher, Anelise; Machado, Geovanna de Castro Morais; Sado-Filho, Joji; Vieira, Liliani Aires Candido; Corrêa-Faria, Patrícia; Hosey, Marie Therese; Costa, Luciane Rezende

2017-04-11

regimes from different perspectives (outcomes). ClinicalTrials.gov, identifier: NCT02447289 . Registered on 11 May 2015, named "Midazolam and Ketamine Effect Administered Through the Nose for Sedation of Children for Dental Treatment (NASO)."

Endocrine manifestations related to inherited metabolic diseases in adults

PubMed Central

2012-01-01

Most inborn errors of metabolism (IEM) are recessive, genetically transmitted diseases and are classified into 3 main groups according to their mechanisms: cellular intoxication, energy deficiency, and defects of complex molecules. They can be associated with endocrine manifestations, which may be complications from a previously diagnosed IEM of childhood onset. More rarely, endocrinopathies can signal an IEM in adulthood, which should be suspected when an endocrine disorder is associated with multisystemic involvement (neurological, muscular, hepatic features, etc.). IEM can affect all glands, but diabetes mellitus, thyroid dysfunction and hypogonadism are the most frequent disorders. A single IEM can present with multiple endocrine dysfunctions, especially those involving energy deficiency (respiratory chain defects), and metal (hemochromatosis) and storage disorders (cystinosis). Non-autoimmune diabetes mellitus, thyroid dysfunction and/or goiter and sometimes hypoparathyroidism should steer the diagnosis towards a respiratory chain defect. Hypogonadotropic hypogonadism is frequent in haemochromatosis (often associated with diabetes), whereas primary hypogonadism is reported in Alström disease and cystinosis (both associated with diabetes, the latter also with thyroid dysfunction) and galactosemia. Hypogonadism is also frequent in X-linked adrenoleukodystrophy (with adrenal failure), congenital disorders of glycosylation, and Fabry and glycogen storage diseases (along with thyroid dysfunction in the first 3 and diabetes in the last). This is a new and growing field and is not yet very well recognized in adulthood despite its consequences on growth, bone metabolism and fertility. For this reason, physicians managing adult patients should be aware of these diagnoses. PMID:22284844

REMOVAL OF ENDOCRINE DISRUPTOR CHEMICALS DURING DRINKING WATER TREATMENT

EPA Science Inventory

A group of chemicals, known as endocrine disruptor chemicals (EDCs) have been identified as having the potential to cause adverse health effects in humans and wildlife. Among this group DDT, PCBs, endosulfan, methoxychlor, diethylphthalate, diethylhexylphthalate, and bisphenol A ...

Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC) Final Report

EPA Pesticide Factsheets

The EDSTAC Report was developed through a deliberative process that encouraged the development of consensus solutions to complex problems and issues related to developing an Endocrine Disruptor Screening Program.

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

Adrenomedullin and endocrine control of immune cells during pregnancy.

PubMed

Matson, Brooke C; Caron, Kathleen M

2014-09-01

The immunology of pregnancy is complex and incompletely understood. Aberrant immune activity in the decidua and in the placenta is believed to play a role in diseases of pregnancy, such as infertility, miscarriage, fetal growth restriction and preeclampsia. Here, we briefly review the endocrine control of uterine natural killer cell populations and their functions by the peptide hormone adrenomedullin. Studies in genetic animal models have revealed the critical importance of adrenomedullin dosage at the maternal-fetal interface, with cells from both the maternal and fetal compartments contributing to essential aspects underlying appropriate uterine receptivity, implantation and vascular remodeling of spiral arteries. These basic insights into the crosstalk between the endocrine and immune systems within the maternal-fetal interface may ultimately translate to a better understanding of the functions and consequences of dysregulated adrenomedullin levels in clinically complicated pregnancies.

75 FR 81605 - Endocrine Disruptor Screening Program (EDSP); Announcing the Availability of a Draft for Weight...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-28

... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OPPT-2010-0877; FRL-8858-9] Endocrine Disruptor Screening Program (EDSP); Announcing the Availability of a Draft for Weight-of-Evidence Guidance Document..., Endocrine disruptors, Screening assays, Weight-of-evidence. Dated: December 20, 2010. Stephen A. Owens...

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. Copyright © 2014 Elsevier Ltd. All rights reserved.

METABOLOMIC STUDIES OF ENDOCRINE DISRUPTION IN SMALL FISH MODELS

EPA Science Inventory

Metabolomics is now being widely used to obtain complementary information to genomic and proteomic studies. To better understand temporal, compensatory and dose responses to endocrine-disrupting chemicals (EDCs) within the hypothalamic-pituitary¬gonadal (HPG) axis, we have carrie...

[Outstanding problems of normal and pathological morphology of the diffuse endocrine system].

PubMed

Iaglov, V V; Iaglova, N V

2011-01-01

The diffuse endocrine system (DES)--a mosaic-cellular endoepithelial gland--is the biggest part of the human endocrine system. Scientists used to consider cells of DES as neuroectodermal. According to modem data cells of DES are different cytogenetic types because they develop from the different embryonic blastophyllum. So that any hormone-active tumors originated from DES of the digestive, respiratory and urogenital system shouldn't be considered as neuroendocrinal tumors. The basic problems of DES morphology and pathology are the creation of scientifically substantiated histogenetic classification of DES tumors.

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...

38 CFR 4.119 - Schedule of ratings-endocrine system.

Code of Federal Regulations, 2014 CFR

2014-07-01

... minute), eye involvement, muscular weakness, loss of weight, and sympathetic nervous system..., loss of weight, and sympathetic nervous system, cardiovascular, or gastrointestinal symptoms 100...-endocrine system. 4.119 Section 4.119 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS...

38 CFR 4.119 - Schedule of ratings-endocrine system.

Code of Federal Regulations, 2013 CFR

2013-07-01

... minute), eye involvement, muscular weakness, loss of weight, and sympathetic nervous system..., loss of weight, and sympathetic nervous system, cardiovascular, or gastrointestinal symptoms 100...-endocrine system. 4.119 Section 4.119 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS...

38 CFR 4.119 - Schedule of ratings-endocrine system.

Code of Federal Regulations, 2012 CFR

2012-07-01

... minute), eye involvement, muscular weakness, loss of weight, and sympathetic nervous system..., loss of weight, and sympathetic nervous system, cardiovascular, or gastrointestinal symptoms 100...-endocrine system. 4.119 Section 4.119 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS...

38 CFR 4.119 - Schedule of ratings-endocrine system.

Code of Federal Regulations, 2011 CFR

2011-07-01

... minute), eye involvement, muscular weakness, loss of weight, and sympathetic nervous system..., loss of weight, and sympathetic nervous system, cardiovascular, or gastrointestinal symptoms 100...-endocrine system. 4.119 Section 4.119 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS...

WASTEWATER TREATMENT AND ITS MANAGEMENT OF ENDOCRINE DISRUPTING CHEMICALS

EPA Science Inventory

Research has shown that wastewater treatment (WWT) can be a significant source of endocrine disrupting chemicals (EDCs) to the environment. WWT can include centralized wastewater treatment plants (WWTPs) or on-site WWT technologies. EDCs found in WWT effluents (aqueous and biosol...

β-D-glucan inhibits endocrine-resistant breast cancer cell proliferation and alters gene expression

PubMed Central

JAFAAR, ZAINAB M.T.; LITCHFIELD, LACEY M.; IVANOVA, MARGARITA M.; RADDE, BRANDIE N.; AL-RAYYAN, NUMAN; KLINGE, CAROLYN M.

2014-01-01

Endocrine therapies have been successfully used for breast cancer patients with estrogen receptor α (ERα) positive tumors, but ∼40% of patients relapse due to endocrine resistance. β-glucans are components of plant cell walls that have immunomodulatory and anticancer activity. The objective of this study was to examine the activity of β-D-glucan, purified from barley, in endocrine-sensitive MCF-7 versus endocrine-resistant LCC9 and LY2 breast cancer cells. β-D-glucan dissolved in DMSO but not water inhibited MCF-7 cell proliferation in a concentration-dependent manner as measured by BrdU incorporation with an IC50 of ∼164±12 μg/ml. β-D-glucan dissolved in DMSO inhibited tamoxifen/endocrine-resistant LCC9 and LY2 cell proliferation with IC50 values of 4.6±0.3 and 24.2±1.4 μg/ml, respectively. MCF-10A normal breast epithelial cells showed a higher IC50 ∼464 μg/ml and the proliferation of MDA-MB-231 triple negative breast cancer cells was not inhibited by β-D-glucan. Concentration-dependent increases in the BAX/BCL2 ratio and cell death with β-D-glucan were observed in MCF-7 and LCC9 cells. PCR array analysis revealed changes in gene expression in response to 24-h treatment with 10 or 50 μg/ml β-D-glucan that were different between MCF-7 and LCC9 cells as well as differences in basal gene expression between the two cell lines. Select results were confirmed by quantitative real-time PCR demonstrating that β-D-glucan increased RASSF1 expression in MCF-7 cells and IGFBP3, CTNNB1 and ERβ transcript expression in LCC9 cells. Our data indicate that β-D-glucan regulates breast cancer-relevant gene expression and may be useful for inhibiting endocrine-resistant breast cancer cell proliferation. PMID:24534923

Boric Acid Is Reproductively Toxic to Adult Xenopus laevis, but Not Endocrine Active.

PubMed

Fort, Douglas J; Fort, Troy D; Mathis, Michael B; Ball, R Wayne

2016-11-01

The potential reproductive and endocrine toxicity of boric acid (BA) in the African clawed frog, Xenopus laevis, was evaluated using a 30-day exposure of adult frogs. Adult female and male frogs established as breeders were exposed to a culture water control and 4 target (nominal) test concentrations [5.0, 7.5, 10.0, and 15 mg boron (B)/L, equivalent to 28.5, 42.8, 57.0, and 85.5 mg BA/L] using flow-through diluter exposure system. The primary endpoints measured were adult survival, growth (weight and snout-vent length [SVL]), necropsy data, reproductive fecundity, and development of progeny (F1) from the exposed frogs. Necropsy endpoints included gonad weight, gonado-somatic index (GSI), ovary profile (oocyte normalcy and stage distribution), sperm count, and dysmorphology. Endocrine endpoints included plasma estradiol (E2), testosterone (T), dihydrotestosteone (DHT), gonadal CYP 19 (aromatase), and gonadal 5α-reductase (5-AR). BA exposure to adult female X. laevis increased the proportion of immature oocytes (< stage II) in the ovaries of females, reduced sperm counts and increased sperm cell dysmorphology frequency in male frogs exposed to 15 mg B/L. No effects on the other general, developmental (F1), or endocrine endpoints were observed. Based on the results of the present study, the no observed adverse effects concentration (NOAEC) for the reproductive endpoints was 10 mg B/L; and 15 mg B/L for reproductive fecundity, F1 embryo larval development, and endocrine function. These results confirmed that although BA is capable of inducing reproductive toxicity at high concentrations, it is not an endocrine disrupting agent. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Conserved genetic pathways controlling the development of the diffuse endocrine system in vertebrates and Drosophila.

PubMed

Hartenstein, Volker; Takashima, Shigeo; Adams, Katrina L

2010-05-01

The midgut epithelium is formed by absorptive enterocytes, secretory cells and endocrine cells. Each of these lineages is derived from the pluripotent progenitors that constitute the embryonic endoderm; the mature midgut retains pools of self-renewing stem cells that continue to produce all lineages. Recent findings in vertebrates and Drosophila shed light on the genetic mechanism that specifies the fate of the different lineages. A pivotal role is played by the Notch signaling pathway that, in a manner that appears to be very similar to the way in which Notch signaling selects neural progenitors within the neurectoderm, distinguishes the fate of secretory/endocrine cells and enterocytes. Proneural genes encoding bHLH transcription factors are expressed and required in prospective endocrine cells; activation of the Notch pathways restricts the number of these cells and promotes enterocyte development. In this review we compare the development of the intestinal endocrine cells in vertebrates and insects and summarize recent findings dealing with genetic pathways controlling this cell type. Copyright 2009. Published by Elsevier Inc.

Endocrine-immune interactions in human endometrium.

PubMed

Kayisli, U A; Guzeloglu-Kayisli, O; Arici, A

2004-12-01

The immune system is a complex entity designed to eliminate foreign intruding antigens and is influenced by and, in turn, influences the function of the reproductive system. Despite the widespread associations between immunology and reproductive medicine, the study of system interactions remains in its infancy. Many diverse facts are accumulating, and pieces of the puzzle are becoming available to provide a clearer picture. In this review article, we focus on the interactions between endocrine and immune systems in the human endometrium. Understanding the molecular pathways in endocrine-immune interactions in the human endometrium is crucial to understand events such as menstrual bleeding, tissue repair and regeneration, inflammation, angiogenesis, blastocyst implantation, and progression of pregnancy. These events require a balanced regulation of endometrial differentiation, proliferation, cell survival, leukocyte recruitment, apoptosis, and angiogenesis by sex steroids. In this review, we first outline the role of survival factors such as phosphoinositol 3-kinase/protein kinase B, PTEN, NFkappaB, and apoptotic molecules (Fas-FasL, Bcl-2). We then discuss their regulation by estrogen and progesterone in the endometrium. We present evidence for direct and/or indirect roles of steroid hormones on the expression of chemotactic cytokines (interleukin-8 and monocyte chemotactic protein-1) and on the survival versus apoptosis of resident endometrial cells (stromal, epithelial, and endothelial cells) and nonresident cells (leukocytes).

[The relative analysis of clinical endocrine features and pathological types of pituitary microadenomas].

PubMed

Yan, Qing; Zhang, Hua-qiu; Wang, He-ping; Guo, Dong-sheng; Lei, Ting; Li, Ling

2010-06-15

To study the relationship between the clinical presentation, endocrinal findings and pathological types in patients with pituitary microadenomas, so as to improve the accuracy of clinical diagnosis and choose the best therapy strategy before the operation. From January 2007 to June 2009, the clinical data of 94 patients who were surgically removed pituitary microadenomas were obtained, including the clinical presentation, endocrinal findings and pathological diagnosis. The analysis was accomplished with Chi-square test. Hormonal symptoms were found in 86 patients (91.5%), it occurred more frequently in immunopositive patients (85/92, 92.4%) than in immunonegative patients (1/2, 50.0%) (P < 0.05). The coincidence of hormonal symptoms and immunohistochemistry diagnosis was 71.7%; 88.9% patients had the symptoms of amenorrhea, galactorrhea and sexual function diseases in prolactin (PRL) positive group and 28.1% patients had the symptoms of gigantism or acromegaly in growth hormone (GH) positive group. The coincidence of endocrinal findings and immunohistochemistry diagnosis was 69.0%; 87.7% patients had high level of blood PRL in PRL positive group and 21.9% patients had high level of blood GH in GH positive group. There is an obvious relationship between the clinical presentation, endocrinal findings and pathological diagnosis in patients with pituitary microadenomas, which may contribute to the clinical diagnosis and treatment of pituitary secreting microadenomas.

DIAGNOSING AND MONITORING ENDOCRINE DYSFUNCTION, DIABETES, AND OBESITY IN A COHORT OF ADULT SURVIVORS OF CHILDHOOD CANCER.

PubMed

Hudspeth, Victoria Rollins; Gold, Stuart Harrison; Clemmons, David Robert

2017-12-01

The 5-year survival rate for childhood cancer has increased to 80%, resulting in a growing population of adult survivors of childhood cancer (ASOCC). Long-term endocrine dysfunction is as high as 63% when screened in research protocols. The purpose of this study was to evaluate the prevalence of endocrine testing, endocrine dysfunction, diabetes, obesity, and endocrinologist visits outside of a research screening protocol. A retrospective chart review was performed for 176 ASOCC who were diagnosed with cancer before age 18, followed at least 10 years, were now at least 18, and had survived to the time of chart review. After a mean follow-up of 15.2 years (range 10-21 years), 33.5% of ASOCC had endocrine dysfunction, excluding obesity and diabetes. These outcomes were more common in those with any radiation (64.8%, P<.0001) or cranial radiation (73.1%, P<.0001). Many subjects had never had certain endocrine tests. Over half (54.6%) of subjects were either overweight or obese. Glycated hemoglobin A1C (A1C) testing was rare, but when performed, 38.1% were abnormal. 71% of subjects had never seen an endocrinologist. Even among subjects with cranial radiation, 65.4% had either never seen an endocrinologist or had not seen one in the past 5 years. This cohort of ASOCC showed high rates of endocrine dysfunction, overweight or obesity, and diabetes in those who had been tested, combined with low rates of testing and endocrinology evaluation. Endocrinologists need to be aware of the endocrine risks in ASOCC, the need for long-term monitoring, and increase their collaboration with oncology. A1C = glycated hemoglobin A1C ASOCC = adult survivors of childhood cancer BMI = body mass index COG = Children's Oncology Group EMR = electronic medical record FSH = follicle-stimulating hormone IGF-1 = insulin-like growth factor 1 LH = luteinizing hormone TSH = thyroid-stimulating hormone.

Endocrine and reproductive dysfunction in men associated with occupational inorganic lead intoxication

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cullen, M.R.; Kayne, R.D.; Robins, J.M.

In an attempt to define a postulated effect of lead on male endocrine function, seven men with symptomatic occupational lead intoxication (maximum whole blood lead levels 66-139 ..mu..g/dl) underwent in-patient endocrine evaluation at the time of diagnosis. Defects in thyroid function probably of central origin, were present in three patients. Six patients had subnormal glucocorticoid production measured by 24-hr urinary 17-hydroxy-corticosteroids and plasma cortisol responses to vasopressin- and/or insulin-induced hypoglycemia. Although serum testosterone concentration was normal in six patients, five had defects in spermatogenesis, including two with ologospermia and two with azoospermia. Repeat examinations after chelation therapy showed only partialmore » improvement. It is concluded that heavy occupational exposure to lead, sufficient to cause clinical poisoning, may be associated with diffuse disturbances of endocrine and reproductive functions in men which are not rapidly reversible with standard treatment. Since men without overt poisoning have not been studied, these results cannot yet be included as sequelae of low-dose exposures.« less

Analysis of Endocrine Disrupting Pesticides by Capillary GC with Mass Spectrometric Detection

PubMed Central

Matisová, Eva; Hrouzková, Svetlana

2012-01-01

Endocrine disrupting chemicals, among them many pesticides, alter the normal functioning of the endocrine system of both wildlife and humans at very low concentration levels. Therefore, the importance of method development for their analysis in food and the environment is increasing. This also covers contributions in the field of ultra-trace analysis of multicomponent mixtures of organic pollutants in complex matrices. With this fact conventional capillary gas chromatography (CGC) and fast CGC with mass spectrometric detection (MS) has acquired a real importance in the analysis of endocrine disrupting pesticide (EDP) residues. This paper provides an overview of GC methods, including sample preparation steps, for analysis of EDPs in a variety of matrices at ultra-trace concentration levels. Emphasis is put on separation method, mode of MS detection and ionization and obtained limits of detection and quantification. Analysis time is one of the most important aspects that should be considered in the choice of analytical methods for routine analysis. Therefore, the benefits of developed fast GC methods are important. PMID:23202677

CCAR1 is required for Ngn3-mediated endocrine differentiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu, Chung-Kuang; Lai, Yi-Chyi; Lin, Yung-Fu

2012-02-10

Highlights: Black-Right-Pointing-Pointer We identify CCAR1 to directly interact with Ngn3. Black-Right-Pointing-Pointer CCAR1 is co-localized with Ngn3 in the nucleus. Black-Right-Pointing-Pointer CCAR1 cooperates with Ngn3 in activating NeuroD expression. Black-Right-Pointing-Pointer CCAR1 is required for Ngn3-mediated PANC-1 transdifferentiation. -- Abstract: Neurogenin3 (Ngn3) is a basic helix-loop-helix transcription factor that specifies pancreatic endocrine cell fates during pancreas development. It can also initiate a transdifferentiation program when expressed in pancreatic exocrine and ductal cells. However, how Ngn3 initiates a transcriptional cascade to achieve endocrine differentiation is still poorly understood. Here, we show that cell cycle and apoptosis regulator 1 (CCAR1), which is a transcriptionalmore » coactivator for nuclear receptors, also interacts with Ngn3. The association between Ngn3 and CCAR1 was verified by pull-down assays and co-immunoprecipitation analyses. Using gene reporter assays, we found that CCAR1 is essential for Ngn3 to activate the expression of the reporter genes containing the NeuroD promoter. Moreover, down-regulation of endogenous CCAR1 in the PANC-1 pancreatic ductal cell line inhibits the transdifferentiation program initiated by Ngn3. CCAR1 is, therefore, a novel partner of Ngn3 in mediating endocrine differentiation.« less

Prevalence of endocrine and genetic abnormalities in boys evaluated systematically for a disorder of sex development

PubMed Central

Nixon, R.; Cerqueira, V.; Kyriakou, A.; Lucas-Herald, A.; McNeilly, J.; McMillan, M.; Purvis, A.I.; Tobias, E.S.; McGowan, R.

2017-01-01

Abstract STUDY QUESTION What is the likelihood of identifying genetic or endocrine abnormalities in a group of boys with 46, XY who present to a specialist clinic with a suspected disorder of sex development (DSD)? SUMMARY ANSWER An endocrine abnormality of the gonadal axis may be present in a quarter of cases and copy number variants (CNVs) or single gene variants may be present in about half of the cases. WHAT IS KNOWN ALREADY Evaluation of 46, XY DSD requires a combination of endocrine and genetic tests but the prevalence of these abnormalities in a sufficiently large group of boys presenting to one specialist multidisciplinary service is unclear. STUDY, DESIGN, SIZE, DURATION This study was a retrospective review of investigations performed on 122 boys. PARTICIPANTS/MATERIALS, SETTING, METHODS All boys who attended the Glasgow DSD clinic, between 2010 and 2015 were included in the study. The median external masculinization score (EMS) of this group was 9 (range 1–11). Details of phenotype, endocrine and genetic investigations were obtained from case records. MAIN RESULTS AND THE ROLE OF CHANCE An endocrine abnormality of gonadal function was present in 28 (23%) with a median EMS of 8.3 (1–10.5) whilst the median EMS of boys with normal endocrine investigations was 9 (1.5–11) (P = 0.03). Endocrine abnormalities included a disorder of gonadal development in 19 (16%), LH deficiency in 5 (4%) and a disorder of androgen synthesis in 4 (3%) boys. Of 43 cases who had array-comparative genomic hybridization (array-CGH), CNVs were reported in 13 (30%) with a median EMS of 8.5 (1.5–11). Candidate gene analysis using a limited seven-gene panel in 64 boys identified variants in 9 (14%) with a median EMS of 8 (1–9). Of the 21 boys with a genetic abnormality, 11 (52%) had normal endocrine investigations. LIMITATIONS, REASONS FOR CAUTION A selection bias for performing array-CGH in cases with multiple congenital malformations may have led to a high yield of CNVs. It

Influence of In Vitro and In Vivo Oxygen Modulation on β Cell Differentiation From Human Embryonic Stem Cells

PubMed Central

Cechin, Sirlene; Álvarez-Cubela, Silvia; Giraldo, Jaime A.; Molano, Ruth D.; Villate, Susana; Ricordi, Camillo; Pileggi, Antonello; Inverardi, Luca

2014-01-01

The possibility of using human embryonic stem (hES) cell-derived β cells as an alternative to cadaveric islets for the treatment of type 1 diabetes is now widely acknowledged. However, current differentiation methods consistently fail to generate meaningful numbers of mature, functional β cells. In order to address this issue, we set out to explore the role of oxygen modulation in the maturation of pancreatic progenitor (PP) cells differentiated from hES cells. We have previously determined that oxygenation is a powerful driver of murine PP differentiation along the endocrine lineage of the pancreas. We hypothesized that targeting physiological oxygen partial pressure (pO2) levels seen in mature islets would help the differentiation of PP cells along the β-cell lineage. This hypothesis was tested both in vivo (by exposing PP-transplanted immunodeficient mice to a daily hyperbaric oxygen regimen) and in vitro (by allowing PP cells to mature in a perfluorocarbon-based culture device designed to carefully adjust pO2 to a desired range). Our results show that oxygen modulation does indeed contribute to enhanced maturation of PP cells, as evidenced by improved engraftment, segregation of α and β cells, body weight maintenance, and rate of diabetes reversal in vivo, and by elevated expression of pancreatic endocrine makers, β-cell differentiation yield, and insulin production in vitro. Our studies confirm the importance of oxygen modulation as a key variable to consider in the design of β-cell differentiation protocols and open the door to future strategies for the transplantation of fully mature β cells. PMID:24375542

Retinol Dehydrogenase-10 Regulates Pancreas Organogenesis and Endocrine Cell Differentiation via Paracrine Retinoic Acid Signaling.

PubMed

Arregi, Igor; Climent, Maria; Iliev, Dobromir; Strasser, Jürgen; Gouignard, Nadège; Johansson, Jenny K; Singh, Tania; Mazur, Magdalena; Semb, Henrik; Artner, Isabella; Minichiello, Liliana; Pera, Edgar M

2016-12-01

Vitamin A-derived retinoic acid (RA) signals are critical for the development of several organs, including the pancreas. However, the tissue-specific control of RA synthesis in organ and cell lineage development has only poorly been addressed in vivo. Here, we show that retinol dehydrogenase-10 (Rdh10), a key enzyme in embryonic RA production, has important functions in pancreas organogenesis and endocrine cell differentiation. Rdh10 was expressed in the developing pancreas epithelium and surrounding mesenchyme. Rdh10 null mutant mouse embryos exhibited dorsal pancreas agenesis and a hypoplastic ventral pancreas with retarded tubulogenesis and branching. Conditional disruption of Rdh10 from the endoderm caused increased mortality, reduced body weight, and lowered blood glucose levels after birth. Endodermal Rdh10 deficiency led to a smaller dorsal pancreas with a reduced density of early glucagon + and insulin + cells. During the secondary transition, the reduction of Neurogenin3 + endocrine progenitors in the mutant dorsal pancreas accounted for fewer α- and β-cells. Changes in the expression of α- and β-cell-specific transcription factors indicated that Rdh10 might also participate in the terminal differentiation of endocrine cells. Together, our results highlight the importance of both mesenchymal and epithelial Rdh10 for pancreogenesis and the first wave of endocrine cell differentiation. We further propose a model in which the Rdh10-expressing exocrine tissue acts as an essential source of RA signals in the second wave of endocrine cell differentiation.

Evaluation of Hydroxyatrazine in the Endocrine Disruptor Screening and Testing Program’s Male and Female Pubertal Protocols.

EPA Science Inventory

Evaluation of Hydroxyatrazine in the Endocrine Disruptor Screening and Testing Program’s Male and Female Pubertal Protocols. ABSTRACT Two critical components of the validation of any in vivo screening assay are to demonstrate sensitivity (ability to detect weak endocrine ...

Environmental Analysis of Endocrine Disrupting Effects from Hydrocarbon Contaminants in the Ecosystem - Final Report - 09/15/1996 - 09/14/2000

DOE Office of Scientific and Technical Information (OSTI.GOV)

McLachlan, John A.

The three major components of the research included: (a) a biotechnology based screening system to identify potential hormone mimics and antagonists (b) an animal screening system to identify biomarkers of endocrine effects and (c) a literature review to identify compounds at various DOE sites that are potential endocrine disruptors. Species of particular interest in this study were those that can serve as sentinel species (e.g., amphibians) and thus provide early warning signals for more widespread impacts on an ecosystem and its wildlife and human inhabitants. The objective of this basic research is to characterize the potential of common hydrocarbon contaminantsmore » in ecosystems to act as endocrine disruptors. Although the endocrine disrupting effects of contaminants such as dioxin and PCBs have been well characterized in both animals and humans, little is known about the capacities of other hydrocarbon contaminants to act as endocrine disruptors. Results obtained from this research project have provided information on endocrine disrupting contaminants for consideration in DOE's risk analyses for determining clean-up levels and priorities at contaminated DOE sites.« less

Occurrence of endocrine-disrupting chemicals in indoor dust

PubMed Central

Hwang, Hyun-Min; Park, Eun-Kee; Young, Thomas M.; Hammock, Bruce D.

2010-01-01

Human exposure to indoor dust enriched with endocrine-disrupting chemicals released from numerous indoor sources has been a focus of increasing concern. Longer residence times and elevated contaminant concentrations in the indoor environment may increase chances of exposure to these contaminants by 1000-fold compared to outdoor exposure. To investigate the occurrence of semi-volatile endocrine-disrupting chemicals, including PBDEs (polybrominated diphenyl ethers), PCBs (polychlorinated biphenyls), phthalates, pyrethroids, DDT (dichlorodiphenyltrichloroethane) and its metabolites, and chlordanes, indoor dust samples were collected from household vacuum cleaner bags provided by 10 apartments and 1 community hall in Davis, California, USA. Chemical analyses show that all indoor dust samples are highly contaminated by target analytes measured in the present study. Di-(2-ethylhexyl)phthalate was the most abundant (104–7630 μg/g) in all samples and higher than other target analytes by 2 to 6 orders of magnitude. PBDEs were also found at high concentrations (1780–25,200 ng/g). Although the use of PCBs has been banned or restricted for decades, some samples had PCBs at levels that are considered to be concerns for human health, indicating that the potential risk posed by PCBs still remains high in the indoor environment, probably due to a lack of dissipation processes and continuous release from the sources. Although the use of some PBDEs is being phased out in some parts of the U.S., this trend may apply to PBDEs as well. We can anticipate that exposure to PBDEs will continue as long as the general public keeps using existing household items such as sofas, mattresses, and carpets that contain PBDEs. This study provides additional information that indoor dust is highly contaminated by persistent and endocrine-disrupting chemicals. PMID:18632138

Aromatase activity modulation by lindane and bisphenol-A in human placental JEG-3 and transfected kidney E293 cells.

PubMed

Nativelle-Serpentini, C; Richard, S; Séralini, G-E; Sourdaine, P

2003-08-01

Aromatase is the cytochrome P-450 involved in converting androgens to estrogens. The cytochrome P-450 family plays a central role in the oxidative metabolism of compounds including environmental pollutants. Since lindane and bisphenol-A (BPA) are two well-characterized endocrine disruptors that have been detected in animals and humans, it was important to learn whether they could affect aromatase activity and consequently estrogen biosynthesis. The present study investigates the effects of BPA and lindane on cytotoxicity, aromatase activity and mRNA levels in human placental JEG-3 cells and transfected human embryonal kidney 293 cells. Both cell lines were exposed to increasing concentrations of lindane (25, 50 and 75 microM) and bisphenol-A (25, 50 and 100 microM) over different time periods (10 min-18 h). As a result, none of these concentrations showed cytotoxicity. After short pre-incubation times (10 min-6 h), aromatase activity was enhanced by both compounds. Longer time incubation (18 h), however, produced dose-related inhibition. Lindane and BPA had no significant effects on CYP19 mRNA levels. Therefore, lindane and BPA modulate aromatase activity suggesting an interaction with the cytochrome P-450 aromatase. This study highlights the endocrine-modulating properties of lindane and bisphenol-A.

Perioperative management of endocrine insufficiency after total pancreatectomy for neoplasia.

PubMed

Maker, Ajay V; Sheikh, Raashid; Bhagia, Vinita

2017-09-01

Indications for total pancreatectomy (TP) have increased, including for diffuse main duct intrapapillary mucinous neoplasms of the pancreas and malignancy; therefore, the need persists for surgeons to develop appropriate endocrine post-operative management strategies. The brittle diabetes after TP differs from type 1/2 diabetes in that patients have absolute deficiency of insulin and functional glucagon. This makes glucose management challenging, complicates recovery, and predisposes to hospital readmissions. This article aims to define the disease, describe the cause for its occurrence, review the anatomy of the endocrine pancreas, and explain how this condition differs from diabetes mellitus in the setting of post-operative management. The morbidity and mortality of post-TP endocrine insufficiency and practical treatment strategies are systematically reviewed from the literature. Finally, an evidence-based treatment algorithm is created for the practicing pancreatic surgeon and their care team of endocrinologists to aid in managing these complex patients. A PubMed, Science Citation Index/Social sciences Citation Index, and Cochrane Evidence-Based Medicine database search was undertaken along with extensive backward search of the references of published articles to identify studies evaluating endocrine morbidity and treatment after TP and to establish an evidence-based treatment strategy. Indications for TP and the etiology of pancreatogenic diabetes are reviewed. After TP, ~80% patients develop hypoglycemic episodes and 40% experience severe hypoglycemia, resulting in 0-8% mortality and 25-45% morbidity. Referral to a nutritionist and endocrinologist for patient education before surgery followed by surgical reevaluation to determine if the patient has the appropriate understanding, support, and resources preoperatively has significantly reduced morbidity and mortality. The use of modern recombinant long-acting insulin analogues, continuous subcutaneous insulin

Growth and Endocrine Function in Tunisian Thalassemia Major Patients.

PubMed

Dhouib, Naouel Guirat; Ben Khaled, Monia; Ouederni, Monia; Besbes, Habib; Kouki, Ridha; Mellouli, Fethi; Bejaoui, Mohamed

2018-01-01

β-thalassemia major (β-TM) is among the most common hereditary disorders imposing high expenses on health-care system worldwide. The patient's survival is dependent on lifetime blood transfusion which leads to iron overload and its toxicity in various organs including endocrine glands. This article provides an overview of endocrine disorders in beta-TM patients. This single center investigation enrolled 28 β-TM patients (16 males, 12 females) regularly transfused with packed red cell since early years of life. For each patient were determined: age, sex, number of transfusions received, history of splenectomy and anthropometric parameters. All patients underwent an evaluation of hormonal status including growth, gonadal, thyroid, adrenal cortex, and parathyroid glands. Dual-energy X-ray absorptiometry was used to diagnose low bone mass. Assessment of iron overload status was performed by measuring the serum ferritin concentration and the results of magnetic resonance imaging T 2 *. Growth retardation was found in 16 of the 28 studied patients (57 %). Thirteen among them had delayed puberty. Spontaneous puberty was achieved in 16 cases. Growth hormone (GH) deficiency was found in 10 cases (35 %). Seventeen among the studied patients (60 %) developed disorders of glucose homeostasis. Subclinical hypothyroidism was found in six patients (21 %). Intensive chelation therapy had allowed the reversibility of this complication in five cases. Adrenal Insufficiency was observed in 9 cases (32%). Hypoparathyroidism has occurred in one case. Ten of the 28 studied patients had low bone mass (35%). Twenty-three of the 28 studied patients (82%) had at least one endocrine complication.

The Endocrine Disrupting Chemical Tolylfluanid Alters Adipocyte Metabolism via Glucocorticoid Receptor Activation

PubMed Central

Neel, Brian A.; Brady, Matthew J.

2013-01-01

Glucocorticoid signaling plays a critical role in regulating energy metabolism. Emerging data implicate environmental endocrine-disrupting chemicals as contributors to the obesity and diabetes epidemics. Previous studies have shown that the phenylsulfamide fungicide tolylfluanid (TF) augments glucocorticoid receptor (GR)-dependent luciferase expression in 3T3-L1 preadipocytes while modulating insulin action in primary murine and human adipocytes. Studies were performed to interrogate glucocorticoid signaling in primary adipocytes exposed to TF. TF mimicked the gene transcription profile of the murine glucocorticoid corticosterone (Cort). Cellular fractionation assays demonstrated that TF treatment promoted the activating serine phosphorylation of GR, augmenting its cytoplasmic-to-nuclear translocation as well as its enrichment at glucocorticoid response elements on the glucocorticoid-induced leucine zipper gene promoter. After acute treatment, Cort or TF promoted insulin receptor substrate-1 (IRS-1) gene and protein expression. Either treatment also enriched GR binding at an identified glucocorticoid response element in the IRS-1 gene. TF or Cort each increased insulin-stimulated lipogenesis, an effect resulting from increased lipogenic gene expression and enhanced insulin-stimulated dephosphorylation of acetyl-coenzyme A carboxylase. The augmentation of insulin-stimulated lipogenesis was mediated through a specific enhancement of Akt phosphorylation at T308. These findings support modulation of IRS-1 levels as a mechanism for glucocorticoid-mediated changes in insulin action in primary adipocytes. Albeit with less affinity than Cort, in silico analysis suggests that TF can interact with the ligand binding pocket of GR. Collectively, these studies identify TF as a structurally unique environmental glucocorticoid. Glucocorticoid signaling may thus represent a novel pathway by which environmental toxicants promote the development of metabolic diseases. PMID:23340252

A path forward in the debate over health impacts of endocrine disrupting chemicals.

PubMed

Zoeller, R Thomas; Bergman, Åke; Becher, Georg; Bjerregaard, Poul; Bornman, Riana; Brandt, Ingvar; Iguchi, Taisen; Jobling, Susan; Kidd, Karen A; Kortenkamp, Andreas; Skakkebaek, Niels E; Toppari, Jorma; Vandenberg, Laura N

2014-12-22

Several recent publications reflect debate on the issue of "endocrine disrupting chemicals" (EDCs), indicating that two seemingly mutually exclusive perspectives are being articulated separately and independently. Considering this, a group of scientists with expertise in basic science, medicine and risk assessment reviewed the various aspects of the debate to identify the most significant areas of dispute and to propose a path forward. We identified four areas of debate. The first is about the definitions for terms such as "endocrine disrupting chemical", "adverse effects", and "endocrine system". The second is focused on elements of hormone action including "potency", "endpoints", "timing", "dose" and "thresholds". The third addresses the information needed to establish sufficient evidence of harm. Finally, the fourth focuses on the need to develop and the characteristics of transparent, systematic methods to review the EDC literature. Herein we identify areas of general consensus and propose resolutions for these four areas that would allow the field to move beyond the current and, in our opinion, ineffective debate.

In silico identification and pharmacological evaluation of novel endocrine disrupting chemicals that act via the ligand-binding domain of the estrogen receptor α.

PubMed

McRobb, Fiona M; Kufareva, Irina; Abagyan, Ruben

2014-09-01

Endocrine disrupting chemicals (EDCs) pose a significant threat to human health, society, and the environment. Many EDCs elicit their toxic effects through nuclear hormone receptors, like the estrogen receptor α (ERα). In silico models can be used to prioritize chemicals for toxicological evaluation to reduce the amount of costly pharmacological testing and enable early alerts for newly designed compounds. However, many of the current computational models are overly dependent on the chemistry of known modulators and perform poorly for novel chemical scaffolds. Herein we describe the development of computational, three-dimensional multi-conformational pocket-field docking, and chemical-field docking models for the identification of novel EDCs that act via the ligand-binding domain of ERα. These models were highly accurate in the retrospective task of distinguishing known high-affinity ERα modulators from inactive or decoy molecules, with minimal training. To illustrate the utility of the models in prospective in silico compound screening, we screened a database of over 6000 environmental chemicals and evaluated the 24 top-ranked hits in an ERα transcriptional activation assay and a differential scanning fluorimetry-based ERα binding assay. Promisingly, six chemicals displayed ERα agonist activity (32nM-3.98μM) and two chemicals had moderately stabilizing effects on ERα. Two newly identified active compounds were chemically related β-adrenergic receptor (βAR) agonists, dobutamine, and ractopamine (a feed additive that promotes leanness in cattle and poultry), which are the first βAR agonists identified as activators of ERα-mediated gene transcription. This approach can be applied to other receptors implicated in endocrine disruption. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Recovery of endocrine and inflammatory mediators following an extended energy deficit.

PubMed

Henning, Paul C; Scofield, Dennis E; Spiering, Barry A; Staab, Jeffery S; Matheny, Ronald W; Smith, Martha A; Bhasin, Shalender; Nindl, Bradley C

2014-03-01

Due to current operational requirements, elite soldiers deploy quickly after completing arduous training courses. Therefore, it is imperative that endocrine and inflammatory mediators have fully recovered. Our objective was to determine whether a short-term (2-6 wk) recovery period was sufficient to restore endocrine and inflammatory homeostasis after sustained energy deficit. Before and immediately after the course, serum concentrations of inflammatory and endocrine markers were taken along with anthropometric measures prior to and immediately after the Army Ranger course. In addition, nine soldiers were assessed between 2 and 6 weeks after the course. This research occurred in a field setting during an intensive 8-week military training course characterized by high-energy expenditure, energy restriction, and sleep deprivation (U.S. Army Ranger School). Twenty-three male soldiers (23.0 ± 2.8 y; 177.6 ± 7.9 cm; 81.0 ± 9.6 kg, 16.8 ± 3.9% body fat) participated in this study. There were no interventions used in this research. Significant changes occurred in circulating total testosterone (-70%), brain-derived neurotrophic factor (-33%), total IGF-1 (-38.7%), free IGF-1 (-41%), IGF binding protein (IGFBP-6; -23.4%), sex-hormone binding globulin (+46%), thyroid stimulating hormone (+85%), IGFBP-1 (+534.4%), IGFBP-2 (+98.3%), IGFBP-3 (+14.7%), IL-4 (+135%), IL-6 (+217%), and IL-8 (+101%). Significant changes in body mass (-8%), bicep (-14%), forearm (-5%), thigh (-7%), and calf (-2%) circumferences, sum of skinfolds (-52%), and percentage body fat (-54%). All anthropometric, inflammatory, and hormonal values, except T3, were restored to baseline levels within 2-6 weeks after the course. Endocrine markers and anthropometric measures were degraded, and inflammatory mediators increased after an extended energy deficit. A short-term recovery of 2-6 weeks was sufficient to restore these mediators.

Immune System: An Emerging Player in Mediating Effects of Endocrine Disruptors on Metabolic Health.

PubMed

Bansal, Amita; Henao-Mejia, Jorge; Simmons, Rebecca A

2018-01-01

The incidence of metabolic disorders like type 2 diabetes and obesity continues to increase. In addition to the well-known contributors to these disorders, such as food intake and sedentary lifestyle, recent research in the exposure science discipline provides evidence that exposure to endocrine-disrupting chemicals like bisphenol A and phthalates via multiple routes (e.g., food, drink, skin contact) also contribute to the increased risk of metabolic disorders. Endocrine-disrupting chemicals (EDCs) can disrupt any aspect of hormone action. It is becoming increasingly clear that EDCs not only affect endocrine function but also adversely affect immune system function. In this review, we focus on human, animal, and in vitro studies that demonstrate EDC exposure induces dysfunction of the immune system, which, in turn, has detrimental effects on metabolic health. These findings highlight how the immune system is emerging as a novel player by which EDCs may mediate their effects on metabolic health. We also discuss studies highlighting mechanisms by which EDCs affect the immune system. Finally, we consider that a better understanding of the immunomodulatory roles of EDCs will provide clues to enhance metabolic function and contribute toward the long-term goal of reducing the burden of environmentally induced diabetes and obesity. Copyright © 2018 Endocrine Society.

An overview of the endocrine and metabolic changes in manned space flight

NASA Astrophysics Data System (ADS)

Leach, Carolyns.

In the years since the Skylab Program, endocrinology and metabolism have gone through stages of development that can be characterized as descriptive, both physiological and biochemical. At the present time, this area demonstrates a significant increase in knowledge of endocrine and metabolic function in physiology and pathology at the biochemical level. The development of sensitive techniques for the measurement of hormones, their precursors and metabolites and the increasing amount of information on integrated endocrine responses in various physiologic processes make it valuable for us to retrospectively consider our space flight findings especially in considering future work.

Impact of three endocrine disruptors, Bisphenol A, Genistein and Vinclozolin on female rat enamel.

PubMed

Jedeon, K; Berdal, A; Babajko, A

2016-06-28

Concerns about the potential adverse effectsof endocrine disruptors (EDs) have been increasingover the last three decades. BisphenolA (BPA), genistein (G) and vinclozolin (V) arethree widely used EDs sharing similar effects.Since populations are exposed to many diverseEDs simultaneously, we demonstratedrecently their impact alone or combined onmale rat tooth enamel. The purpose of thisstudy was therefore to assess their effects onfemale rat tooth enamel in order to understandwhy they are differentially sensitive. Ratswere exposed daily in utero and after birth tolow doses of EDs during the critical fetal andsuckling periods when amelogenesis takesplace. Enamel of rats exposed to EDs presentedopaque areas of hypomineralization. Theproportion of affected rats was the highestin the groups of rats treated with BPA aloneand higher in males than in females (in all thegroups). Comparison of enamel key gene expressionlevels showed modulations of Klk4and Enamelin in males but no significant variationsin females. These findings show thatfemale rats are less affected than males bythe three EDs chosen in this study and suggestthat enamel hypomineralization may differbetween males and females.

Survival and human papillomavirus in oropharynx cancer in TAX 324: a subset analysis from an international phase III trial.

PubMed

Posner, M R; Lorch, J H; Goloubeva, O; Tan, M; Schumaker, L M; Sarlis, N J; Haddad, R I; Cullen, K J

2011-05-01

The association between human papillomavirus (HPV) and overall survival (OS) in oropharynx cancer (OPC) was retrospectively examined in TAX 324, a phase III trial of sequential therapy for locally advanced head and neck cancer. Accrual for TAX 324 was completed in 2003 and data updated through 2008. Pretherapy tumor biopsies were studied by PCR for human papillomavirus type 16 and linked to OS, progression-free survival (PFS) and demographics. Of 264 patients with OPC, 111 (42%) had evaluable biopsies; 56 (50%) were HPV+ and 55 (50%) were HPV-. HPV+ patients were significantly younger (54 versus 58 years, P = 0.02), had T1/T2 primary cancers (49% versus 20%, P = 0.001), and had a performance status of zero (77% versus 49%, P = 0.003). OS and PFS were better for HPV+ patients (OS, hazard ratio = 0.20, P < 0.0001). Local-regional failure was less in HPV+ patients (13% versus 42%, P = 0.0006); at 5 years, 82% of HPV+ patients were alive compared with 35% of HPV- patients (P < 0.0001). HPV+ OPC has a different biology compared with HPV- OPC; 5-year OS, PFS, and local-regional control are unprecedented. These results support the possibility of selectively reducing therapy and long-term morbidity in HPV+ OPC while preserving survival and approaching HPV- disease with more aggressive treatment.

Neuroendocrine and behavioral implications of endocrine disrupting chemicals in quail

USGS Publications Warehouse

Ottinger, M.A.; Abdelnabi, M.A.; Henry, P.; McGary, S.; Thompson, N.; Wu, J.M.

2001-01-01

Studies in our laboratory have focused on endocrine, neuroendocrine, and behavioral components of reproduction in the Japanese quail. These studies considered various stages in the life cycle, including embryonic development, sexual maturation, adult reproductive function, and aging. A major focus of our research has been the role of neuroendocrine systems that appear to synchronize both endocrine and behavioral responses. These studies provide the basis for our more recent research on the impact of endocrine disrupting chemicals (EDCs) on reproductive function in the Japanese quail. These endocrine active chemicals include pesticides, herbicides, industrial products, and plant phytoestrogens. Many of these chemicals appear to mimic vertebrate steroids, often by interacting with steroid receptors. However, most EDCs have relatively weak biological activity compared to native steroid hormones. Therefore, it becomes important to understand the mode and mechanism of action of classes of these chemicals and sensitive stages in the life history of various species. Precocial birds, such as the Japanese quail, are likely to be sensitive to EDC effects during embryonic development, because sexual differentiation occurs during this period. Accordingly, adult quail may be less impacted by EDC exposure. Because there are a great many data available on normal development and reproductive function in this species, the Japanese quail provides an excellent model for examining the effects of EDCs. Thus, we have begun studies using a Japanese quail model system to study the effects of EDCs on reproductive endocrine and behavioral responses. In this review, we have two goals: first, to provide a summary of reproductive development and sexual differentiation in intact Japanese quail embryos, including ontogenetic patterns in steroid hormones in the embryonic and maturing quail. Second, we discuss some recent data from experiments in our laboratory in which EDCs have been tested in

Rapid effects of estrogens on behavior: environmental modulation and molecular mechanisms.

PubMed

Laredo, Sarah A; Villalon Landeros, Rosalina; Trainor, Brian C

2014-10-01

Estradiol can modulate neural activity and behavior via both genomic and nongenomic mechanisms. Environmental cues have a major impact on the relative importance of these signaling pathways with significant consequences for behavior. First we consider how photoperiod modulates nongenomic estrogen signaling on behavior. Intriguingly, short days permit rapid effects of estrogens on aggression in both rodents and song sparrows. This highlights the importance of considering photoperiod as a variable in laboratory research. Next we review evidence for rapid effects of estradiol on ecologically-relevant behaviors including aggression, copulation, communication, and learning. We also address the impact of endocrine disruptors on estrogen signaling, such as those found in corncob bedding used in rodent research. Finally, we examine the biochemical mechanisms that may mediate rapid estrogen action on behavior in males and females. A common theme across these topics is that the effects of estrogens on social behaviors vary across different environmental conditions. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparative toxicity, oxidative stress and endocrine disruption potential of plasticizers in JEG-3 human placental cells.

PubMed

Pérez-Albaladejo, Elisabet; Fernandes, Denise; Lacorte, Silvia; Porte, Cinta

2017-02-01

Plasticizers are suspected to be toxic and/or to modulate or disrupt the endocrine system of humans and to cross the placental barrier, being embryonic and fetal development a particularly vulnerable period. This work investigates the comparative toxicity and ability to interfere with the synthesis of steroids and to generate reactive oxygen species (ROS) of a selected number of plasticizers, including bisphenol A (BPA), nonyl- (NP) and octylphenol (OP), benzyl butyl phthalate (BBP), dibutyl phthalate (DBP), di(2-ethylhexyl)phthalate (DEHP) and dimethyl phthalate (DMP), in the human placenta JEG-3 cells. Moreover, the bioavailability of chemicals in culture medium has been investigated. After 24h exposure, OP and NP showed the highest cytotoxicity (EC 50 : 36-40μM) followed by BPA (138-219μM), whereas no significant toxicity was observed for phthalates. Notwithstanding, BBP and DBP significantly decreased P450 aromatase activity (experimental IC 50 : 14-15μM), while NP and OP (20μM) increased the activity. Overall, this study evidences the differential toxicity and ability to modulate placental aromatase activity of some of the compounds nowadays used as plasticizers, and highlights the need of an accurate determination of the bioavailability of chemicals to improve the sensitivity of in-vitro tests. Copyright © 2016 Elsevier B.V. All rights reserved.

Simultaneous effects of endocrine disruptor bisphenol A and flavonoid fisetin on progesterone production by granulosa cells.

PubMed

Bujnakova Mlynarcikova, Alzbeta; Scsukova, Sona

2018-04-01

In the present study, we aimed to examine effects of different concentrations of the endocrine disruptor Bisphenol A (BPA; 1 nM, 1 μM, 100 μM) and the flavonoid fisetin (1, 10, 25, 50 μM), individually and in combinations, on steroidogenic function of porcine ovarian granulosa cells (GCs) represented by progesterone production. We confirmed that BPA inhibited progesterone production by GCs at the highest concentration. Fisetin reduced gonadotropin-stimulated progesterone synthesis dose-dependently, and in this manner, fisetin impaired progesterone production when added to BPA-treated GCs. The mechanisms of the inhibitory effects of the combinations included a significant down-regulation of the key steroidogenesis-related genes (STAR, CYP11A1, HSD3B). Our findings suggest for the first time that fisetin might interfere with ovarian steroidogenesis, and might not have beneficial but rather aggravating effects in terms of modulating progesterone synthesis altered by high concentrations of BPA. Copyright © 2018 Elsevier B.V. All rights reserved.

The US EPA's Endocrine Disruptor Screening Program: In VItro and In Vivo Mammalian Tier 1 Screening Assays

EPA Science Inventory

In response to emerging concerns that environmental chemicals may have adverse effects on human health by altering the function of the endocrine system, the Food Quality Protection Act mandated that the U.S. EPA develop and implement an endocrine disruptor screening program (EDSP...

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...