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

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.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.

Original languageEnglish
Pages (from-to)2795-2806
Number of pages12
JournalEndocrinology
Volume156
Issue number8
DOIs
Publication statusPublished - Aug 1 2015

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Alligators and Crocodiles
Androgen Receptors
Androgens
vinclozolin
Hormones
Oviparity
Flutamide
Dichlorodiphenyl Dichloroethylene
Androgen Antagonists
Steroid Receptors
Cytoplasmic and Nuclear Receptors
Research
Transcriptional Activation
Reproduction
Vertebrates
Testis
Complementary DNA
Maintenance
Ligands
Amino Acids

All Science Journal Classification (ASJC) codes

  • Endocrinology

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Identification and characterization of the androgen receptor from the American Alligator, Alligator mississippiensis. / Miyagawa, Shinichi; Yatsu, Ryohei; Kohno, Satomi; Doheny, Brenna M.; Ogino, Yukiko; Ishibashi, Hiroshi; Katsu, Yoshinao; Ohta, Yasuhiko; Guillette, Louis J.; Iguchi, Taisen.

In: Endocrinology, Vol. 156, No. 8, 01.08.2015, p. 2795-2806.

Research output: Contribution to journalArticle

Miyagawa, S, Yatsu, R, Kohno, S, Doheny, BM, Ogino, Y, Ishibashi, H, Katsu, Y, Ohta, Y, Guillette, LJ & Iguchi, T 2015, 'Identification and characterization of the androgen receptor from the American Alligator, Alligator mississippiensis', Endocrinology, vol. 156, no. 8, pp. 2795-2806. https://doi.org/10.1210/en.2015-1037
Miyagawa, Shinichi ; Yatsu, Ryohei ; Kohno, Satomi ; Doheny, Brenna M. ; Ogino, Yukiko ; Ishibashi, Hiroshi ; Katsu, Yoshinao ; Ohta, Yasuhiko ; Guillette, Louis J. ; Iguchi, Taisen. / Identification and characterization of the androgen receptor from the American Alligator, Alligator mississippiensis. In: Endocrinology. 2015 ; Vol. 156, No. 8. pp. 2795-2806.
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