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      Genes, Gender, Environment, and Novel Functions of Estrogen Receptor Beta in the Susceptibility to Neurodevelopmental Disorders

      review-article
      Author(s): , *
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      Publication date (Electronic):
      Journal: Brain Sciences
      Publisher: MDPI
      Keywords: estrogen, testosterone, dyslexia, aromatase, brain, neurodevelopment, sex-difference, hormone, BPA, epigenetics

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          Abstract

          Many neurological disorders affect men and women differently regarding prevalence, progression, and severity. It is clear that many of these disorders may originate from defective signaling during fetal or perinatal brain development, which may affect males and females differently. Such sex-specific differences may originate from chromosomal or sex-hormone specific effects. This short review will focus on the estrogen receptor beta (ERβ) signaling during perinatal brain development and put it in the context of sex-specific differences in neurodevelopmental disorders. We will discuss ERβ’s recent discovery in directing DNA de-methylation to specific sites, of which one such site may bear consequences for the susceptibility to the neurological reading disorder dyslexia. We will also discuss how dysregulations in sex-hormone signaling, like those evoked by endocrine disruptive chemicals, may affect this and other neurodevelopmental disorders in a sex-specific manner through ERβ.

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          Exposure of the U.S. Population to Bisphenol A and 4-tertiary-Octylphenol: 2003–2004

          Antonia M Calafat, Xiaoyun Ye, Lee-Yang Wong … (2007)
          Background Bisphenol A (BPA) and 4-tertiary-octylphenol (tOP) are industrial chemicals used in the manufacture of polycarbonate plastics and epoxy resins (BPA) and nonionic surfactants (tOP). These products are in widespread use in the United States. Objectives We aimed to assess exposure to BPA and tOP in the U.S. general population. Methods We measured the total (free plus conjugated) urinary concentrations of BPA and tOP in 2,517 participants ≥ 6 years of age in the 2003–2004 National Health and Nutrition Examination Survey using automated solid-phase extraction coupled to isotope dilution–high-performance liquid chromatography–tandem mass spectrometry. Results BPA and tOP were detected in 92.6% and 57.4% of the persons, respectively. Least square geometric mean (LSGM) concentrations of BPA were significantly lower in Mexican Americans than in non-Hispanic blacks (p = 0.006) and non-Hispanic whites (p = 0.007); LSGM concentrations for non-Hispanic blacks and non-Hispanic whites were not statistically different (p = 0.21). Females had statistically higher BPA LSGM concentrations than males (p = 0.043). Children had higher concentrations than adolescents (p $45,000/year). Conclusions Urine concentrations of total BPA differed by race/ethnicity, age, sex, and household income. These first U.S. population representative concentration data for urinary BPA and tOP should help guide public health research priorities, including studies of exposure pathways, potential health effects, and risk assessment.
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            Organizing action of prenatally administered testosterone propionate on the tissues mediating mating behavior in the female guinea pig.

            CHARLES PHOENIX, ROBERT W. GOY, ARNOLD A. GERALL … (1959)
            Article 0 comments Cited 299 times – based on 0 reviews     Review now
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              Estrogen actions in the brain and the basis for differential action in men and women: a case for sex-specific medicines.

              Glenda Gillies, Simon McArthur (2010)
              The classic view of estrogen actions in the brain was confined to regulation of ovulation and reproductive behavior in the female of all mammalian species studied, including humans. Burgeoning evidence now documents profound effects of estrogens on learning, memory, and mood as well as neurodevelopmental and neurodegenerative processes. Most data derive from studies in females, but there is mounting recognition that estrogens play important roles in the male brain, where they can be generated from circulating testosterone by local aromatase enzymes or synthesized de novo by neurons and glia. Estrogen-based therapy therefore holds considerable promise for brain disorders that affect both men and women. However, as investigations are beginning to consider the role of estrogens in the male brain more carefully, it emerges that they have different, even opposite, effects as well as similar effects in male and female brains. This review focuses on these differences, including sex dimorphisms in the ability of estradiol to influence synaptic plasticity, neurotransmission, neurodegeneration, and cognition, which, we argue, are due in a large part to sex differences in the organization of the underlying circuitry. There are notable sex differences in the incidence and manifestations of virtually all central nervous system disorders, including neurodegenerative disease (Parkinson's and Alzheimer's), drug abuse, anxiety, and depression. Understanding the cellular and molecular basis of sex differences in brain physiology and responses to estrogen and estrogen mimics is, therefore, vitally important for understanding the nature and origins of sex-specific pathological conditions and for designing novel hormone-based therapeutic agents that will have optimal effectiveness in men or women.
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                Author and article information

                Contributors
                Yu Ping Tang: Role: Academic Editor
                Journal
                Journal ID (nlm-ta): Brain Sci
                Journal ID (iso-abbrev): Brain Sci
                Journal ID (publisher-id): brainsci
                Title: Brain Sciences
                Publisher: MDPI
                ISSN (Electronic): 2076-3425
                Publication date (Electronic): 23 February 2017
                Publication date Collection: March 2017
                Volume: 7
                Issue: 3
                Electronic Location Identifier: 24
                Affiliations
                Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge 14183, Sweden; mukesh.varshney@ 123456ki.se
                Author notes
                [* ]Correspondence: ivan.nalvarte@ 123456ki.se ; Tel.: +46-852-481-059
                Article
                Publisher ID: brainsci-07-00024
                DOI: 10.3390/brainsci7030024
                PMC ID: 5366823
                PubMed ID: 28241485
                SO-VID: 6891c3a4-2940-45e8-bc8d-0b7fc4d34171
                Copyright © © 2017 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 17 October 2016
                Date accepted : 17 February 2017
                Categories
                Subject: Review

                Keywords: estrogen,testosterone,dyslexia,aromatase,brain,neurodevelopment,sex-difference,hormone,bpa,epigenetics
                Data availability:
                Keywords: estrogen, testosterone, dyslexia, aromatase, brain, neurodevelopment, sex-difference, hormone, bpa, epigenetics

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