Endocrine disruption through membrane estrogen receptors and novel pathways leading to rapid toxicological and epigenetic effects. Issue 187 (March 2019)

• Record Type: Journal Article
• Authors: Rosenfeld, Cheryl S.; Cooke, Paul S.
• Is Part Of: Journal of steroid biochemistry and molecular biology. Issue 187(2019)
• Page Start: 106
• Page End: 117
• Publication Date: 2019-03
• Subjects: 2-Br 2-bromohexadecanoic acid -- AKT protein kinase B -- APT acyl protein thioesterase(s), e.g. APT-1 and -2 -- BPA bisphenol A -- BPS bisphenol S -- BPA bovine serum albumin -- CAV1/Cav1 caveolin-1 -- Cav3 caveolin-3 -- CREB cAMP response element-binding protein -- DDT 1, 1-trichloro-2, 2-bis[4-chlorophenyl]ethane -- DE-71 penta-bromodiphenyl -- DE-79 octa-bromodiphenyl -- DEHP diethylhexyl phthalate -- DES diethylstilbestrol -- E2 17β-estradiol -- EDC endocrine disrupting chemical(s) -- EE2 17α-ethinyl estradiol -- EGF epidermal growth factor -- Emem transgene human ESR1 E-domain, a N-terminal fragment of the CNS protein neuromodulin -- ERE estrogen response element -- ERK extracellular signal-regulated kinase -- ESR estrogen receptor(s) -- Esr1KO estrogen receptor 1 knockout -- EZH2 enhancer of Zeste homolog 2 -- GPCR G protein-coupled receptors -- GPER G protein-coupled estrogen receptor -- H2NES transgenic mice that retain non-genomic ESR1 signaling but lack genomic ESR1 signaling due to mutation in the hinge region of ESR1 -- H3 histone H3 -- JNK c-jun-N-terminal kinase -- MAPK mitogen-activated protein kinase -- mESR membrane estrogen receptor(s) -- MOER membrane-only ESR1 -- nESR nuclear estrogen receptor(s) -- NOER nuclear-only ESR1 -- OCP organochlorine pesticides -- PAT palmitoyl-acyltransferase(s), e.g. DHHC-7 and -21 -- PBDE polybrominated diphenyl ether -- PI3K phosphoinositol 3-kinase -- PK protein kinase(s) -- PRC2 polycomb repressive complex 2 -- PRR5L/Prr5l proline rich 5 like -- SHBG sex hormone binding globulins; Xenoestrogen -- Calcium signaling -- MAPK -- ERK -- Non-genomic actions -- NOER; Steroid hormones -- Periodicals; Biochemistry -- Periodicals; Hormones -- Periodicals; Molecular Biology -- Periodicals; Hormones stéroïdes -- Périodiques; Steroid hormones; Periodicals; 572.579
• DOI: 10.1016/j.jsbmb.2018.11.007
• Languages: English
• ISSNs: 0960-0760

Abstract

Graphical abstract: Highlights: Estrogens can signal through membrane (m) and nuclear (n) estrogen receptor 1 (ESR1). mESR1 is from same transcript as nESR1 but directed to membrane via palmitoylation. E2 and xenoestrogen signaling through mESR1 induces rapid cellular changes. Endocrine disrupting chemicals (EDC) might affect shuttling of ESR to membrane. Mice lacking mESR1 or nESR1 can be used to test EDC-effects via mESR1 +/- nESR1. Abstract: Estrogen binding to estrogen receptors (ESR) triggers signaling cascades within cells. Historically, a major emphasis has been characterizing estrogen-induced genomic actions resulting from binding to nuclear estrogen receptor 1 (nESR1). However, recent evidence indicates the first receptors estrogens encounter as they enter a cell, membrane ESR1 (mESR1), also play crucial roles. Membrane and nuclear ESR are derived from the same transcripts but the former are directed to the membrane via palmitoylation. Binding and activation of mESR1 leads to rapid fluctuations in cAMP and Ca +2 and stimulation of protein kinase pathways. Endocrine disrupting chemicals (EDC) that mimic 17β-estradiol can signal through mESR1 and elicit non-genomic effects. Most current EDC studies have focused on genomic actions via nESR1. However, increasing number of studies have begun to examine potential EDC effects mediated through mESR1, and some EDC might have higher potency for signaling through mESR1 than nESR1. The notion that such chemicals might also affect mESR1 signaling via palmitoylation and depalmitoylation pathways has also begun to gain currency. Recent development of transgenic mice that lack either mESR1 or nESR1, while retaining functional ESR1 in the other compartment, will allow more precise in vivo approaches to determine EDC effects through nESR1 and/or mESR1. It is increasingly becoming apparent in this quickly evolving field that EDC directly affect mESR and estrogen signaling, but such chemicals can also affect proportion of ESR reaching the membrane. Future EDC studies should be designed to consider the full range of effects through mESR alone and in combination with nESR.