Rapid actions of xenoestrogens disrupt normal estrogenic signaling

Cheryl S. Watson, Guangzhen Hu, Adriana A. Paulucci-Holthauzen

    Research output: Contribution to journalArticle

    16 Citations (Scopus)

    Abstract

    Some chemicals used in consumer products or manufacturing (e.g. plastics, surfactants, pesticides, resins) have estrogenic activities; these xenoestrogens (XEs) chemically resemble physiological estrogens and are one of the major categories of synthesized compounds that disrupt endocrine actions. Potent rapid actions of XEs via nongenomic mechanisms contribute significantly to their disruptive effects on functional endpoints (e.g. cell proliferation/death, transport, peptide release). Membrane-initiated hormonal signaling in our pituitary cell model is predominantly driven by mERα with mERβ and GPR30 participation. We visualized ERα on plasma membranes using many techniques in the past (impeded ligands, antibodies to ERα) and now add observations of epitope proximity with other membrane signaling proteins. We have demonstrated a range of rapid signals/protein activations by XEs including: calcium channels, cAMP/PKA, MAPKs, G proteins, caspases, and transcription factors. XEs can cause disruptions of the oscillating temporal patterns of nongenomic signaling elicited by endogenous estrogens. Concentration effects of XEs are nonmonotonic (a trait shared with natural hormones), making it difficult to design efficient (single concentration) toxicology tests to monitor their harmful effects. A plastics monomer, bisphenol A, modified by waste treatment (chlorination) and other processes causes dephosphorylation of extracellular-regulated kinases, in contrast to having no effects as it does in genomic signaling. Mixtures of XEs, commonly found in contaminated environments, disrupt the signaling actions of physiological estrogens even more severely than do single XEs. Understanding the features of XEs that drive these disruptive mechanisms will allow us to redesign useful chemicals that exclude estrogenic or anti-estrogenic activities.

    Original languageEnglish (US)
    Pages (from-to)36-42
    Number of pages7
    JournalSteroids
    Volume81
    DOIs
    StatePublished - 2014

    Fingerprint

    Estrogens
    Plastics
    Halogenation
    Calcium Channels
    Caspases
    GTP-Binding Proteins
    Pesticides
    Surface-Active Agents
    Toxicology
    Epitopes
    Membrane Proteins
    Membranes
    Cell Death
    Transcription Factors
    Phosphotransferases
    Cell Proliferation
    Cell Membrane
    Consumer products
    Hormones
    Waste treatment

    Keywords

    • Endocrine disruptors
    • Environmental estrogens
    • Estrogen receptor-α
    • G proteins
    • Mitogen-activated protein kinases
    • Nongenomic

    ASJC Scopus subject areas

    • Biochemistry
    • Clinical Biochemistry
    • Endocrinology
    • Molecular Biology
    • Organic Chemistry
    • Pharmacology

    Cite this

    Rapid actions of xenoestrogens disrupt normal estrogenic signaling. / Watson, Cheryl S.; Hu, Guangzhen; Paulucci-Holthauzen, Adriana A.

    In: Steroids, Vol. 81, 2014, p. 36-42.

    Research output: Contribution to journalArticle

    Watson, Cheryl S. ; Hu, Guangzhen ; Paulucci-Holthauzen, Adriana A. / Rapid actions of xenoestrogens disrupt normal estrogenic signaling. In: Steroids. 2014 ; Vol. 81. pp. 36-42.
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