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      Organizational and activational effects of estrogenic endocrine disrupting chemicals Translated title: Efeitos de organização e ativação dos desreguladores estrogênicos

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          Abstract

          Endocrine disruption is a hypothesis of common mode of action that may define a set of structurally varied chemicals, both natural and synthetic. Their common mode of action may suggest that they produce or contribute to similar toxic effects, although this has been difficult to demonstrate. Insights from developmental biology suggest that development of hormone sensitive systems, such as the brain and the genitourinary tract, may be particularly sensitive to EDCs. Because these systems are both organized and later activated by hormones, the brain and vagina may be valuable model systems to study the toxicity of EDCs in females and to elucidate mechanisms whereby early exposures appear to affect long term function.

          Translated abstract

          A desregulação endócrina é uma hipótese de um modo de ação comum capaz de definir um conjunto de substâncias químicas estruturalmente variadas, tanto naturais quanto sintéticas. O modo de ação comum pode sugerir que produzam ou contribuam para efeitos tóxicos semelhantes, embora tal hipótese tenha sido difícil de demonstrar. Evidências provenientes da biologia do desenvolvimento sugerem que o desenvolvimento de sistemas sensíveis aos hormônios, tais como o cérebro e o trato genito-urinário, podem ser particularmente sensíveis aos desreguladores endócrinos. Uma vez que tais sistemas são organizados, e depois ativados, por hormônios, o cérebro e a vagina podem representar modelos importantes para estudar a toxicidade dos desreguladores endócrinos e para elucidar os mecanismos pelos quais parecem afetar a função a longo prazo.

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          Most cited references133

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          Adenocarcinoma of the vagina. Association of maternal stilbestrol therapy with tumor appearance in young women.

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            Comparative distribution of estrogen receptor-alpha and -beta mRNA in the rat central nervous system.

            Estrogen plays a profound role in regulating the structure and function of many neuronal systems in the adult rat brain. The actions of estrogen were thought to be mediated by a single nuclear estrogen receptor (ER) until the recent cloning of a novel ER (ER-beta). To ascertain which ER is involved in the regulation of different brain regions, the present study compared the distribution of the classical (ER-alpha) and novel (ER-beta) forms of ER mRNA-expressing neurons in the central nervous system (CNS) of the rat with in situ hybridization histochemistry. Female rat brain, spinal cord, and eyes were frozen, and cryostat sections were collected on slides, hybridized with [35S]-labeled antisense riboprobes complimentary to ER-alpha or ER-beta mRNA, stringently washed, and opposed to emulsion. The results of these studies revealed the presence of ER-alpha and ER-beta mRNA throughout the rostral-caudal extent of the brain and spinal cord. Neurons of the olfactory bulb, supraoptic, paraventricular, suprachiasmatic, and tuberal hypothalamic nuclei, zona incerta, ventral tegmental area, cerebellum (Purkinje cells), laminae III-V, VIII, and IX of the spinal cord, and pineal gland contained exclusively ER-beta mRNA. In contrast, only ER-alpha hybridization signal was seen in the ventromedial hypothalamic nucleus and subfornical organ. Perikarya in other brain regions, including the bed nucleus of the stria terminalis, medial and cortical amygdaloid nuclei, preoptic area, lateral habenula, periaqueductal gray, parabrachial nucleus, locus ceruleus, nucleus of the solitary tract, spinal trigeminal nucleus and superficial laminae of the spinal cord, contained both forms of ER mRNA. Although the cerebral cortex and hippocampus contained both ER mRNAs, the hybridization signal for ER-alpha mRNA was very weak compared with ER-beta mRNA. The results of these in situ hybridization studies provide detailed information about the distribution of ER-alpha and ER-beta mRNAs in the rat CNS. In addition, this comparative study provides evidence that the region-specific expression of ER-alpha, ER-beta, or both may be important in determining the physiological responses of neuronal populations to estrogen action.
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              Tissue distribution and quantitative analysis of estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta) messenger ribonucleic acid in the wild-type and ERalpha-knockout mouse.

              Until recently, only a single type of estrogen receptor (ER) was thought to exist and mediate the genomic effects of the hormone 17beta-estradiol in mammalian tissues. However, the cloning of a gene encoding a second type of ER, termed ERbeta, from the mouse, rat, and human has prompted a reevaluation of the estrogen signaling system. Based on in vitro studies, the ERbeta protein binds estradiol with an affinity similar to that of the classical ER (now referred to as ERalpha) and is able to mediate the effects of estradiol in transfected mammalian cell lines. Essential to further investigations of the possible physiological roles of ERbeta, and its possible interactions with ERalpha, are data on the tissue distribution of the two ER types. Herein, we have described the optimization and use of an RNase protection assay able to detect and distinguish messenger RNA (mRNA) transcripts from both the ERalpha and ERbeta genes in the mouse. Because this assay is directly quantitative, a comparison of the levels of expression within various tissues was possible. In addition, the effect of disruption of the ERalpha gene on the expression of the ERbeta gene was also investigated using the ERalpha-knockout (ERKO) mouse. Transcripts encoding ERalpha were detected in all the wild-type tissues assayed from both sexes. In the female reproductive tract, the highest expression of ERbeta mRNA was observed in the ovary and showed great variation among individual animals; detectable levels were observed in the uterus and oviduct, whereas mammary tissue was negative. In the male reproductive tract, significant expression of ERbeta was seen in the prostate and epididymis, whereas the testes were negative. In other tissues of both sexes, the hypothalamus and lung were clearly positive for both ERalpha and ERbeta mRNA. The ERKO mice demonstrated slightly reduced levels of ERbeta mRNA in the ovary, prostate, and epididymis. These data, in combination with the several described phenotypes in both sexes of the ERKO mouse, suggest that the biological functions of the ERbeta protein may be dependent on the presence of ERalpha in certain cell types and tissues. Further characterization of the physiological phenotypes in the ERKO mice may elucidate possible ERbeta specific actions.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Journal
                csp
                Cadernos de Saúde Pública
                Cad. Saúde Pública
                Escola Nacional de Saúde Pública Sergio Arouca, Fundação Oswaldo Cruz (Rio de Janeiro )
                1678-4464
                April 2002
                : 18
                : 2
                : 495-504
                Affiliations
                [1 ] Bloomberg School of Public Health U.S.A.
                [2 ] University of Maryland United States
                [3 ] George Washington University United States
                Article
                S0102-311X2002000200014
                e50dff8f-1692-40cf-8ca5-6a62c0a24df3

                http://creativecommons.org/licenses/by/4.0/

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                SciELO Brazil

                Self URI (journal page): http://www.scielosp.org/scielo.php?script=sci_serial&pid=0102-311X&lng=en
                Categories
                Health Policy & Services

                Public health
                Chemical Compound Exposure,Brain,Vagina,Endocrine Disruptors,Exposição a Produtos Químicos,Cérebro,Desreguladores Endócrinos

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