Talk:Endocrine System - Abnormalities
| About Discussion Pages |
|---|
Glossary Links
Cite this page: Hill, M.A. (2024, April 25) Embryology Endocrine System - Abnormalities. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Endocrine_System_-_Abnormalities |
2019
Endocrine Disrupting Chemicals: An Occult Mediator of Metabolic Disease
Front Endocrinol (Lausanne). 2019 Mar 1;10:112. doi: 10.3389/fendo.2019.00112. eCollection 2019.
Papalou O1, Kandaraki EA1, Papadakis G2, Diamanti-Kandarakis E1.
Endocrine disrupting chemicals (EDCs), a heterogeneous group of exogenous chemicals that can interfere with any aspect of endogenous hormones, represent an emerging global threat for human metabolism. There is now considerable evidence that the observed upsurge of metabolic disease cannot be fully attributed to increased caloric intake, physical inactivity, sleep deficit, and ageing. Among environmental factors implicated in the global deterioration of metabolic health, EDCs have drawn the biggest attention of scientific community, and not unjustifiably. EDCs unleash a coordinated attack toward multiple components of human metabolism, including crucial, metabolically-active organs such as hypothalamus, adipose tissue, pancreatic beta cells, skeletal muscle, and liver. Specifically, EDCs' impact during critical developmental windows can promote the disruption of individual or multiple systems involved in metabolism, via inducing epigenetic changes that can permanently alter the epigenome in the germline, enabling changes to be transmitted to the subsequent generations. The clear effect of this multifaceted attack is the manifestation of metabolic disease, clinically expressed as obesity, metabolic syndrome, diabetes mellitus, and non-alcoholic fatty liver disease. Although limitations of EDCs research do exist, there is no doubt that EDCs constitute a crucial parameter of the global deterioration of metabolic health we currently encounter. KEYWORDS: diabetes mellitus; endocrine disrupting chemical (EDC); enviromental chemicals; environmental contaminants; human metabolism; insulin resistance; obesity; obesogens PMID: 30881345
Immunomodulatory effects of synthetic endocrine disrupting chemicals on the development and functions of human immune cells
Environ Int. 2019 Apr;125:350-364. doi: 10.1016/j.envint.2019.01.078. Epub 2019 Feb 8.
Nowak K1, Jabłońska E2, Ratajczak-Wrona W2.
Abstract
Endocrine disrupting chemicals (EDCs) are added to food, cosmetics, plastic packages, and children's toys and have thus become an integral part of the human environment. In the last decade, there has been increasing interest in the effect of EDCs on human health, including their impact on the immune system. So far, researchers have proved that EDCs (e.g. bisphenols, phthalates, triclosan, phenols, propanil, tetrachlorodibenzo-p-dioxin, diethylstilbestrol, tributyltin (TBT), and parabens) affect the development, functions, and lifespan of immune cells (e.g., monocytes, neutrophils, mast cells, eosinophils, lymphocytes, dendritic cells, and natural killers). In this review, we have summarized the current knowledge of the multivariable influence of EDCs on immune cells and underlined the novel approach to EDC studies, including dose-dependent effects and low-dose effects. We discuss critically the possible relationship between exposure to EDCs and immunity related diseases (e.g. allergy, asthma, diabetes, and lupus). Moreover, based on the literature, we construct a model of possible mechanisms of EDC action on immune cells at cellular, molecular, and epigenetic levels.
Copyright © 2019 Elsevier Ltd. All rights reserved.
KEYWORDS: Bisphenol a; EDC; Immunology system; Immunotoxicity; Lymphocyte; Monocyte PMID: 30743143 DOI: 10.1016/j.envint.2019.01.078
2018
Maternal hormonal milieu influence on fetal brain development
Brain Behav. 2018 Jan 24;8(2):e00920. doi: 10.1002/brb3.920. eCollection 2018 Feb.
Miranda A1,2,3, Sousa N1,2,4. Author information Abstract An adverse maternal hormonal environment during pregnancy can be associated with abnormal brain growth. Subtle changes in fetal brain development have been observed even for maternal hormone levels within the currently accepted physiologic ranges. In this review, we provide an update of the research data on maternal hormonal impact on fetal neurodevelopment, giving particular emphasis to thyroid hormones and glucocorticoids. Thyroid hormones are required for normal brain development. Despite serum TSH appearing to be the most accurate indicator of thyroid function in pregnancy, maternal serum free T4 levels in the first trimester of pregnancy are the major determinant of postnatal psychomotor development. Even a transient period of maternal hypothyroxinemia at the beginning of neurogenesis can confer a higher risk of expressive language and nonverbal cognitive delays in offspring. Nevertheless, most recent clinical guidelines advocate for targeted high-risk case finding during first trimester of pregnancy despite universal thyroid function screening. Corticosteroids are determinant in suppressing cell proliferation and stimulating terminal differentiation, a fundamental switch for the maturation of fetal organs. Not surprisingly, intrauterine exposure to stress or high levels of glucocorticoids, endogenous or synthetic, has a molecular and structural impact on brain development and appears to impair cognition and increase anxiety and reactivity to stress. Limbic regions, such as hippocampus and amygdala, are particularly sensitive. Repeated doses of prenatal corticosteroids seem to have short-term benefits of less respiratory distress and fewer serious health problems in offspring. Nevertheless, neurodevelopmental growth in later childhood and adulthood needs further clarification. Future studies should address the relevance of monitoring the level of thyroid hormones and corticosteroids during pregnancy in the risk stratification for impaired postnatal neurodevelopment. KEYWORDS: fetal neurodevelopment; fetal programming; glucocorticoids; maternal hormones; melatonin; oxytocin; sex steroids; thyroid hormones PMID: 29484271 PMCID: PMC5822586 DOI: 10.1002/brb3.920
Perinatal exposure to an environmentally relevant mixture of phthalates results in a lower number of neurons and synapses in the medial prefrontal cortex and decreased cognitive flexibility in adult male and female rats
J Neurosci. 2018 Jul 16. pii: 0607-18. doi: 10.1523/JNEUROSCI.0607-18.2018. [Epub ahead of print]
Kougias DG1, Sellinger EP1, Willing J2, Juraska JM3,1.
Abstract
The growth and organization of the developing brain is known to be influenced by hormones, but little is known about whether disruption of hormones affects cortical regions, like the medial prefrontal cortex (mPFC). This region is particularly important given its involvement in executive functions and implication in the pathology of many neuropsychiatric disorders. Here, we examine the long-term effects of perinatal exposure to endocrine-disrupting compounds, the phthalates, on the mPFC and associated behavior. This investigation is pertinent as humans are ubiquitously exposed to phthalates through a variety of consumer products and phthalates can readily cross the placenta and be delivered to offspring via lactation. Pregnant dams orally consumed an environmentally relevant mixture of phthalates at 0, 200, or 1000 μg/kg/day through pregnancy and for 10 days while lactating. As adults, offspring were tested in an attentional set-shifting task, which assesses cognitive flexibility. Brains were also examined in adulthood for stereological quantification of the number of neurons, glia, and synapses within the mPFC. We found that, independent of sex, perinatal phthalate exposure at either dose resulted in a reduction in neuron number, synapse number, and size of the mPFC and a deficit in cognitive flexibility. Interestingly, the number of synapses was correlated with cognitive flexibility, such that rats with fewer synapses were less cognitively flexible than those with more synapses. These results demonstrate that perinatal phthalate exposure can have long-term effects on the cortex and behavior of both male and female rats.SIGNIFICANCE STATEMENTHumans globally are exposed on a daily basis to a variety of phthalates, which are endocrine-disrupting chemicals. The effects of phthalate exposure on the developing brain, especially on cognitively relevant regions like the medial prefrontal cortex (mPFC), is not known. Here, we use a rat model of human prenatal exposure to an environmentally relevant mixture of phthalates and find there is an appreciable reduction in neuron number, synapse number, and size of the mPFC and a deficit in cognitive flexibility. These results may have serious implications for humans given the mPFC is involved in executive functions and is implicated in the pathology of many neuropsychiatric disorders. PMID: 30012688 DOI: 10.1523/JNEUROSCI.0607-18.2018
2015
Transplacental passage of antimicrobial paraben preservatives
J Expo Sci Environ Epidemiol. 2015 May 6. doi: 10.1038/jes.2015.27. [Epub ahead of print]
Towers CV1, Terry PD2, Lewis D3, Howard B1, Chambers W3, Armistead C3, Weitz B1, Porter S1, Borman CJ4, Kennedy RC5, Chen J5.
Abstract
Parabens are widely used preservatives suspected of being endocrine disruptors, with implications for human growth and development. The most common paraben found in consumer products is methylparaben. To date, no study has examined whether these substances cross the human placenta. A total of 100 study subjects (50 mother-child pairs) were enrolled at two medical institutions, serving primarily African-American and Caucasian women, respectively. A maternal blood sample was drawn on admission and a paired cord blood sample was obtained at delivery. Of the 50 mothers, 47 (94%) showed methylparaben in their blood (mean level 20.41 ng/l), and 47 in cords bloods (mean level 36.54 ng/l). There were 45 mother-child pairs where methylparaben was found in both samples. Of these, the fetal level was higher than the maternal level in 23 (51%). For butylparaben, only 4 mothers (8%) showed detectable levels (mean 40.54 ng/l), whereas 8 cord blood samples (16%) were positive (mean 32.5 ng/l). African-American mothers and infants showed higher prevalence of detectable levels (P=0.017). Methylparaben and butylparaben demonstrate transplacental passage. Additional studies are needed to examine potential differences in exposure by geography and demographics, what products are used by pregnant women that contain these preservatives, as well as any potential long-term effects in the growth and development of exposed children.Journal of Exposure Science and Environmental Epidemiology advance online publication, 6 May 2015; doi:10.1038/jes.2015.27.
PMID 25944699
Effect-directed identification of endocrine disruptors in plastic baby teethers
J Appl Toxicol. 2015 May 18. doi: 10.1002/jat.3159. [Epub ahead of print]
Berger E1,2, Potouridis T3, Haeger A4, Püttmann W3, Wagner M1.
Abstract
Concerns have been raised regarding the human health effects of endocrine disrupting chemicals (EDCs), many of which are associated with and leaching from plastics. As infants are particularly vulnerable to EDCs, we have investigated whether plastic teethers for babies represent a relevant source of exposure. Applying effect-directed analysis, we use bioassays to screen teethers, toys used to soothe a baby's teething ache, for endocrine activity and chemical analysis to identify the causative compounds. We detected significant endocrine activity in two of 10 plastic teethers. Those samples leached estrogenic and/or antiandrogenic activity as detected in the Yeast Estrogen Screen and Yeast Antiandrogen Screen. After sample fractionation, gas chromatography-mass spectrometry non-target screening revealed that methyl-, ethyl- and propylparaben were responsible for the observed estrogenic and antiandrogenic activity in one product. The second product is likely to contain at least six different antiandrogenic compounds that remain so far unidentified. This study demonstrates that plastic teethers can be a source of infant exposure to well-established and unknown EDCs. Because of their limited value to the product, but potential toxicity, manufacturers should critically revisit the use of parabens in plastic teethers and further toys. Moreover, plastic teethers might leach EDCs that escape routine analysis and, thus, toxicological evaluation. The resulting uncertainty in product safety poses a problem to consumers, producers and regulators that remain to be resolved. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd. KEYWORDS: bioassay; chemical analysis; ethyl-4-hydroxybenzoate; in vitro; methyl-4-hydroxybenzoate; migration; paraben; polymer; propyl-4-hydroxybenzoate; reporter-gene assays PMID 25988240
2014
Rare diseases in clinical endocrinology: a taxonomic classification system
J Endocrinol Invest. 2014 Nov 7. [Epub ahead of print]
Marcucci G1, Cianferotti L, Beck-Peccoz P, Capezzone M, Cetani F, Colao A, Davì MV, Degli Uberti E, Del Prato S, Elisei R, Faggiano A, Ferone D, Foresta C, Fugazzola L, Ghigo E, Giacchetti G, Giorgino F, Lenzi A, Malandrino P, Mannelli M, Marcocci C, Masi L, Pacini F, Opocher G, Radicioni A, Tonacchera M, Vigneri R, Zatelli MC, Brandi ML.
Abstract
PURPOSE: Rare endocrine-metabolic diseases (REMD) represent an important area in the field of medicine and pharmacology. The rare diseases of interest to endocrinologists involve all fields of endocrinology, including rare diseases of the pituitary, thyroid and adrenal glands, paraganglia, ovary and testis, disorders of bone and mineral metabolism, energy and lipid metabolism, water metabolism, and syndromes with possible involvement of multiple endocrine glands, and neuroendocrine tumors. Taking advantage of the constitution of a study group on REMD within the Italian Society of Endocrinology, consisting of basic and clinical scientists, a document on the taxonomy of REMD has been produced. METHODS AND RESULTS: This document has been designed to include mainly REMD manifesting or persisting into adulthood. The taxonomy of REMD of the adult comprises a total of 166 main disorders, 338 including all variants and subtypes, described into 11 tables. CONCLUSIONS: This report provides a complete taxonomy to classify REMD of the adult. In the future, the creation of registries of rare endocrine diseases to collect data on cohorts of patients and the development of common and standardized diagnostic and therapeutic pathways for each rare endocrine disease is advisable. This will help planning and performing intervention studies in larger groups of patients to prove the efficacy, effectiveness, and safety of a specific treatment.
PMID 25376364
2012
Diethylstilbestrol induces vaginal adenosis by disrupting SMAD/RUNX1-mediated cell fate decision in the Müllerian duct epithelium
Dev Biol. 2013 Sep 1;381(1):5-16. doi: 10.1016/j.ydbio.2013.06.024. Epub 2013 Jul 4.
Laronda MM1, Unno K, Ishi K, Serna VA, Butler LM, Mills AA, Orvis GD, Behringer RR, Deng C, Sinha S, Kurita T.
Abstract
Women exposed to diethylstilbestrol (DES) in utero frequently develop vaginal adenosis, from which clear cell adenocarcinoma can arise. Despite decades of extensive investigation, the molecular pathogenesis of DES-associated vaginal adenosis remains elusive. Here we report that DES induces vaginal adenosis by inhibiting the BMP4/Activin A-regulated vaginal cell fate decision through a downregulation of RUNX1. BMP4 and Activin A produced by vaginal mesenchyme synergistically activated the expression of ΔNp63, thus deciding vaginal epithelial cell fate in the Müllerian duct epithelial cells (MDECs) via direct binding of SMADs on the highly conserved 5' sequence of ΔNp63. Therefore, mice in which Smad4 was deleted in MDECs failed to express ΔNp63 in vaginal epithelium and developed adenosis. This SMAD-dependent ΔNp63 activation required RUNX1, a binding partner of SMADs. Conditional deletion of Runx1 in the MDECs induced adenosis in the cranial portion of vagina, which mimicked the effect of developmental DES-exposure. Furthermore, neonatal DES exposure downregulated RUNX1 in the fornix of the vagina, where DES-associated adenosis is frequently found. This observation strongly suggests that the downregulation of RUNX1 is the cause of vaginal adenosis. However, once cell fate was determined, the BMP/Activin-SMAD/RUNX1 signaling pathway became dispensable for the maintenance of ΔNp63 expression in vaginal epithelium. Instead, the activity of the ΔNp63 locus in vaginal epithelium was maintained by a ΔNp63-dependent mechanism. This is the first demonstration of a molecular mechanism through which developmental chemical exposure causes precancerous lesions by altering cell fate. Copyright © 2013 Elsevier Inc. All rights reserved. KEYWORDS: DES daughter; Endocrine disruptor; Vaginal clear cell adenocarcinoma; p63
PMID 23830984 PMCID: PMC3947918 DOI: 10.1016/j.ydbio.2013.06.024
2012
Orphanet J Rare Dis. 2012 Jan 28;7:11.
Vantyghem MC, Dobbelaere D, Mention K, Wemeau JL, Saudubray JM, Douillard C. Source Service d'Endocrinologie et Maladies Métaboliques, 1, Rue Polonovski, Hôpital C Huriez, Centre Hospitalier Régional et Universitaire de Lille, 59037 Lille cedex, France. mcvantyghem@gmail.com
Abstract
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
