title: Identification and Characterization of the Androgen Receptor From the American Alligator, Alligator mississippiensis.
abstract: Androgens are essential for the development, reproduction, and health throughout the life span of vertebrates, particularly during the initiation and maintenance of male sexual characteristics. Androgen signaling is mediated by the androgen receptor (AR), a member of the steroid nuclear receptor superfamily. Mounting evidence suggests that environmental factors, such as exogenous hormones or contaminants that mimic hormones, can disrupt endocrine signaling and function. The American alligator (Alligator mississippiensis), a unique model for ecological research in that it exhibits environment-dependent sex determination, is oviparous and long lived. Alligators from a contaminated environment exhibit low reproductive success and morphological disorders of the testis and phallus in neonates and juveniles, both associated with androgen signaling; thus, the alterations are hypothesized to be related to disrupted androgen signaling. However, this line of research has been limited because of a lack of information on the alligator AR gene. Here, we isolated A mississippiensis AR homologs (AmAR) and evaluated receptor-hormone/chemical interactions using a transactivation assay. We showed that AmAR responded to all natural androgens and their effects were inhibited by cotreatment with antiandrogens, such as flutamide, p,p'-dichlorodiphenyldichloroethylene, and vinclozolin. Intriguingly, we found a spliced form of the AR from alligator cDNA, which lacks seven amino acids within the ligand-binding domain that shows no response to androgens. Finally, we have initial data on a possible dominant-negative function of the spliced form of the AR against androgen-induced AmAR.
authors.affiliation: Okazaki Institute for Integrative Bioscience (S.M., R.Y., Y.Og., T.I.), National Institute for Basic Biology, National Institutes of Natural Sciences, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Aichi 444-8787, Japan; Department of Obstetrics and Gynecology (S.K., B.M.D., L.J.G.), Medical University of South Carolina and Hollings Marine Laboratory, Charleston, South Carolina 29412; Department of Life Environmental Conservation (H.I.), Faculty of Agriculture, Ehime University, Matsuyama, Ehime 790-8566, Japan; Department of Biological Sciences (Y.K.), Hokkaido University, Sapporo 060-0810, Japan; and Department of Veterinary Medicine (Y.Oh.), Faculty of Agriculture, Tottori University, Tottori, Tottori 680-8553, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Miyagawa
authors.affiliation: Okazaki Institute for Integrative Bioscience (S.M., R.Y., Y.Og., T.I.), National Institute for Basic Biology, National Institutes of Natural Sciences, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Aichi 444-8787, Japan; Department of Obstetrics and Gynecology (S.K., B.M.D., L.J.G.), Medical University of South Carolina and Hollings Marine Laboratory, Charleston, South Carolina 29412; Department of Life Environmental Conservation (H.I.), Faculty of Agriculture, Ehime University, Matsuyama, Ehime 790-8566, Japan; Department of Biological Sciences (Y.K.), Hokkaido University, Sapporo 060-0810, Japan; and Department of Veterinary Medicine (Y.Oh.), Faculty of Agriculture, Tottori University, Tottori, Tottori 680-8553, Japan.
authors.forename: Ryohei
authors.initials: R
authors.lastname: Yatsu
authors.affiliation: Okazaki Institute for Integrative Bioscience (S.M., R.Y., Y.Og., T.I.), National Institute for Basic Biology, National Institutes of Natural Sciences, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Aichi 444-8787, Japan; Department of Obstetrics and Gynecology (S.K., B.M.D., L.J.G.), Medical University of South Carolina and Hollings Marine Laboratory, Charleston, South Carolina 29412; Department of Life Environmental Conservation (H.I.), Faculty of Agriculture, Ehime University, Matsuyama, Ehime 790-8566, Japan; Department of Biological Sciences (Y.K.), Hokkaido University, Sapporo 060-0810, Japan; and Department of Veterinary Medicine (Y.Oh.), Faculty of Agriculture, Tottori University, Tottori, Tottori 680-8553, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Kohno
authors.affiliation: Okazaki Institute for Integrative Bioscience (S.M., R.Y., Y.Og., T.I.), National Institute for Basic Biology, National Institutes of Natural Sciences, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Aichi 444-8787, Japan; Department of Obstetrics and Gynecology (S.K., B.M.D., L.J.G.), Medical University of South Carolina and Hollings Marine Laboratory, Charleston, South Carolina 29412; Department of Life Environmental Conservation (H.I.), Faculty of Agriculture, Ehime University, Matsuyama, Ehime 790-8566, Japan; Department of Biological Sciences (Y.K.), Hokkaido University, Sapporo 060-0810, Japan; and Department of Veterinary Medicine (Y.Oh.), Faculty of Agriculture, Tottori University, Tottori, Tottori 680-8553, Japan.
authors.forename: Brenna M
authors.initials: BM
authors.lastname: Doheny
authors.affiliation: Okazaki Institute for Integrative Bioscience (S.M., R.Y., Y.Og., T.I.), National Institute for Basic Biology, National Institutes of Natural Sciences, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Aichi 444-8787, Japan; Department of Obstetrics and Gynecology (S.K., B.M.D., L.J.G.), Medical University of South Carolina and Hollings Marine Laboratory, Charleston, South Carolina 29412; Department of Life Environmental Conservation (H.I.), Faculty of Agriculture, Ehime University, Matsuyama, Ehime 790-8566, Japan; Department of Biological Sciences (Y.K.), Hokkaido University, Sapporo 060-0810, Japan; and Department of Veterinary Medicine (Y.Oh.), Faculty of Agriculture, Tottori University, Tottori, Tottori 680-8553, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Ogino
authors.affiliation: Okazaki Institute for Integrative Bioscience (S.M., R.Y., Y.Og., T.I.), National Institute for Basic Biology, National Institutes of Natural Sciences, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Aichi 444-8787, Japan; Department of Obstetrics and Gynecology (S.K., B.M.D., L.J.G.), Medical University of South Carolina and Hollings Marine Laboratory, Charleston, South Carolina 29412; Department of Life Environmental Conservation (H.I.), Faculty of Agriculture, Ehime University, Matsuyama, Ehime 790-8566, Japan; Department of Biological Sciences (Y.K.), Hokkaido University, Sapporo 060-0810, Japan; and Department of Veterinary Medicine (Y.Oh.), Faculty of Agriculture, Tottori University, Tottori, Tottori 680-8553, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishibashi
authors.affiliation: Okazaki Institute for Integrative Bioscience (S.M., R.Y., Y.Og., T.I.), National Institute for Basic Biology, National Institutes of Natural Sciences, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Aichi 444-8787, Japan; Department of Obstetrics and Gynecology (S.K., B.M.D., L.J.G.), Medical University of South Carolina and Hollings Marine Laboratory, Charleston, South Carolina 29412; Department of Life Environmental Conservation (H.I.), Faculty of Agriculture, Ehime University, Matsuyama, Ehime 790-8566, Japan; Department of Biological Sciences (Y.K.), Hokkaido University, Sapporo 060-0810, Japan; and Department of Veterinary Medicine (Y.Oh.), Faculty of Agriculture, Tottori University, Tottori, Tottori 680-8553, Japan.
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Katsu
authors.affiliation: Okazaki Institute for Integrative Bioscience (S.M., R.Y., Y.Og., T.I.), National Institute for Basic Biology, National Institutes of Natural Sciences, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Aichi 444-8787, Japan; Department of Obstetrics and Gynecology (S.K., B.M.D., L.J.G.), Medical University of South Carolina and Hollings Marine Laboratory, Charleston, South Carolina 29412; Department of Life Environmental Conservation (H.I.), Faculty of Agriculture, Ehime University, Matsuyama, Ehime 790-8566, Japan; Department of Biological Sciences (Y.K.), Hokkaido University, Sapporo 060-0810, Japan; and Department of Veterinary Medicine (Y.Oh.), Faculty of Agriculture, Tottori University, Tottori, Tottori 680-8553, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Ohta
authors.affiliation: Okazaki Institute for Integrative Bioscience (S.M., R.Y., Y.Og., T.I.), National Institute for Basic Biology, National Institutes of Natural Sciences, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Aichi 444-8787, Japan; Department of Obstetrics and Gynecology (S.K., B.M.D., L.J.G.), Medical University of South Carolina and Hollings Marine Laboratory, Charleston, South Carolina 29412; Department of Life Environmental Conservation (H.I.), Faculty of Agriculture, Ehime University, Matsuyama, Ehime 790-8566, Japan; Department of Biological Sciences (Y.K.), Hokkaido University, Sapporo 060-0810, Japan; and Department of Veterinary Medicine (Y.Oh.), Faculty of Agriculture, Tottori University, Tottori, Tottori 680-8553, Japan.
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Guillette
authors.affiliation: Okazaki Institute for Integrative Bioscience (S.M., R.Y., Y.Og., T.I.), National Institute for Basic Biology, National Institutes of Natural Sciences, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Aichi 444-8787, Japan; Department of Obstetrics and Gynecology (S.K., B.M.D., L.J.G.), Medical University of South Carolina and Hollings Marine Laboratory, Charleston, South Carolina 29412; Department of Life Environmental Conservation (H.I.), Faculty of Agriculture, Ehime University, Matsuyama, Ehime 790-8566, Japan; Department of Biological Sciences (Y.K.), Hokkaido University, Sapporo 060-0810, Japan; and Department of Veterinary Medicine (Y.Oh.), Faculty of Agriculture, Tottori University, Tottori, Tottori 680-8553, Japan.
authors.forename: Taisen
authors.initials: T
authors.lastname: Iguchi
mesh_terms: D000489:Alligators and Crocodiles / Q000235:genetics*; D000818:Animals; D003001:Cloning, Molecular; D004625:Embryo, Nonmammalian; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D008297:Male; D008958:Models, Molecular; D010802:Phylogeny; D011944:Receptors, Androgen / Q000737:chemistry / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D011944:Receptors, Androgen