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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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              Organizational and activational effects of sex steroids on brain and behavior: a reanalysis.

              The actions of sex steroids on brain and behavior traditionally have been divided into organizational and activational effects. Organizational effects are permanent and occur early in development; activational effects are transient and occur throughout life. Over the past decade, experimental results have accumulated which do not fit such a simple two-process theory. Specifically, the characteristics said to distinguish organizational and activational effects on behavior are sometimes mixed, as when permanent effects occur in adulthood. Attempts to determine whether specific cellular processes are uniquely associated with either organizational or activational effects are unsuccessful. These considerations blur the organizational-activational distinction sufficiently to suggest that a rigid dichotomy is no longer tenable.
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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/

                History
                Product

                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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