title: Human sex hormone-binding globulin binding affinities of 125 structurally diverse chemicals and comparison with their binding to androgen receptor, estrogen receptor, and α-fetoprotein.
abstract: One endocrine disruption mechanism is through binding to nuclear receptors such as the androgen receptor (AR) and estrogen receptor (ER) in target cells. The concentration of a chemical in serum is important for its entry into the target cells to bind the receptors, which is regulated by the serum proteins. Human sex hormone-binding globulin (SHBG) is the major transport protein in serum that can bind androgens and estrogens and thus change a chemical's availability to enter the target cells. Sequestration of an androgen or estrogen in the serum can alter the chemical elicited AR- and ER-mediated responses. To better understand the chemical-induced endocrine activity, we developed a competitive binding assay using human pregnancy plasma and measured the binding to the human SHBG for 125 structurally diverse chemicals, most of which were known to bind AR and ER. Eighty seven chemicals were able to bind the human SHBG in the assay, whereas 38 chemicals were nonbinders. Binding data for human SHBG are compared with that for rat α-fetoprotein, ER and AR. Knowing the binding profiles between serum and nuclear receptors will improve assessment of a chemical's potential for endocrine disruption. The SHBG binding data reported here represent the largest data set of structurally diverse chemicals tested for human SHBG binding. Utilization of the SHBG binding data with AR and ER binding data could enable better evaluation of endocrine disrupting potential of chemicals through AR- and ER-mediated responses since sequestration in serum could be considered.
authors.affiliation: *Division of Bioinformatics and Biostatistics, Division of Systems Biology, Division of Genetic and Molecular Toxicology and Office of Scientific Coordination, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas 72079 huixiao.hong@fda.hhs.gov.
authors.forename: Huixiao
authors.initials: H
authors.lastname: Hong
authors.affiliation: *Division of Bioinformatics and Biostatistics, Division of Systems Biology, Division of Genetic and Molecular Toxicology and Office of Scientific Coordination, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas 72079.
authors.forename: William S
authors.initials: WS
authors.lastname: Branham
authors.affiliation: *Division of Bioinformatics and Biostatistics, Division of Systems Biology, Division of Genetic and Molecular Toxicology and Office of Scientific Coordination, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas 72079.
authors.forename: Hui Wen
authors.initials: HW
authors.lastname: Ng
authors.affiliation: *Division of Bioinformatics and Biostatistics, Division of Systems Biology, Division of Genetic and Molecular Toxicology and Office of Scientific Coordination, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas 72079.
authors.forename: Carrie L
authors.initials: CL
authors.lastname: Moland
authors.affiliation: *Division of Bioinformatics and Biostatistics, Division of Systems Biology, Division of Genetic and Molecular Toxicology and Office of Scientific Coordination, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas 72079.
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Dial
authors.affiliation: *Division of Bioinformatics and Biostatistics, Division of Systems Biology, Division of Genetic and Molecular Toxicology and Office of Scientific Coordination, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas 72079.
authors.forename: Hong
authors.initials: H
authors.lastname: Fang
authors.affiliation: *Division of Bioinformatics and Biostatistics, Division of Systems Biology, Division of Genetic and Molecular Toxicology and Office of Scientific Coordination, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas 72079.
authors.forename: Roger
authors.initials: R
authors.lastname: Perkins
authors.affiliation: *Division of Bioinformatics and Biostatistics, Division of Systems Biology, Division of Genetic and Molecular Toxicology and Office of Scientific Coordination, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas 72079.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sheehan
authors.affiliation: *Division of Bioinformatics and Biostatistics, Division of Systems Biology, Division of Genetic and Molecular Toxicology and Office of Scientific Coordination, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas 72079.
authors.forename: Weida
authors.initials: W
authors.lastname: Tong
mesh_terms: D001667:Binding, Competitive; D052244:Endocrine Disruptors / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D011944:Receptors, Androgen / Q000737:chemistry* / Q000378:metabolism; D011960:Receptors, Estrogen / Q000737:chemistry* / Q000378:metabolism; D012738:Sex Hormone-Binding Globulin / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D000509:alpha-Fetoproteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D052244:Endocrine Disruptors; D008024:Ligands; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D012738:Sex Hormone-Binding Globulin; D000509:alpha-Fetoproteins
keywords: alpha-fetoprotein; androgen receptor; binding affinity; endocrine disruptor; estrogen receptor; sex hormone-binding globulin