Identification and characterization of the androgen receptor from the American Alligator, Alligator mississippiensis

Shinichi Miyagawa, Ryohei Yatsu, Satomi Kohno, Brenna M. Doheny, Yukiko Ogino, Hiroshi Ishibashi, Yoshinao Katsu, Yasuhiko Ohta, Louis J. Guillette, Taisen Iguchi

研究成果: Contribution to journalArticle査読

7 被引用数 (Scopus)

抄録

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.WeshowedthatAmARresponded to all natural androgens and their effects were inhibited by cotreatment with antiandrogens, such as flutamide, p,p-dichlorodiphenyldichloroethylene, and vinclozolin. Intriguingly,wefound a spliced form of theAR 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.

本文言語英語
ページ(範囲)2795-2806
ページ数12
ジャーナルEndocrinology
156
8
DOI
出版ステータス出版済み - 8 1 2015
外部発表はい

All Science Journal Classification (ASJC) codes

  • 内分泌学

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