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Zebrafish androgen receptor: isolation, molecular, and biochemical characterization
Örebro University, School of Science and Technology.
Örebro University, School of Science and Technology.ORCID iD: 0000-0001-9713-2365
Örebro University, School of Science and Technology.ORCID iD: 0000-0001-7336-6335
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2008 (English)In: Biology of Reproduction, ISSN 0006-3363, E-ISSN 1529-7268, Vol. 78, no 2, p. 361-369Article in journal (Refereed) Published
Abstract [en]

Androgens play an important role in male sexual differentiation and development. They exert their function by binding to and activating the androgen receptor (Ar), a member of the steroid hormone receptor superfamily. Here, we report on the isolation and characterization of zebrafish Ar. The complete transcript of zebrafish ar is 5.3 kb long encoding a putative polypeptide of 868 amino acids. Our experimental and bioinformatic analysis has found a single ar locus in zebrafish. Phylogenetic analysis using the ligand-binding domain showed that the zebrafish Ar clustered with its cyprinid orthologs to form a separate group, which was closer to the beta clade than to the alpha clade. Tissue-specific expression analysis revealed that the ar mRNA was expressed ubiquitously in all adult tissues tested, with sexually dimorphic expression in the gonad and muscle. While the ar transcript was maternally deposited into the embryo, signs of zygotic expression could be detected as early as 24 h after fertilization, and the expression level increased substantially afterwards. When analyzed during gonad development, the expression level of ar mRNA at 4 wk after fertilization was similar in both developing gonads but later became higher in the transforming testis, suggesting a potential role during male gonad differentiation. We also combined theoretical modeling with in vitro experiments to show that the zebrafish Ar is preferentially activated by 11-ketotestosterone.

Place, publisher, year, edition, pages
Champaign, Ill.: Society for the Study of Reproduction , 2008. Vol. 78, no 2, p. 361-369
Keywords [en]
Androgens/*metabolism/pharmacology, Animals, Chromosome Mapping, Cloning; Molecular, Computer Simulation, DNA; Complementary/genetics, Female, Gene Expression, Gonads/growth & development, Male, Molecular Sequence Data, Phylogeny, RNA; Messenger/metabolism, Receptors; Androgen/agonists/*classification/*genetics, Sequence Homology; Amino Acid, Testosterone/analogs & derivatives/pharmacology, Transcription; Genetic, Transfection, Zebrafish/genetics/*growth & development, Zebrafish Proteins/*genetics
National Category
Natural Sciences Biological Sciences
Research subject
biologi
Identifiers
URN: urn:nbn:se:oru:diva-3557DOI: 10.1095/​biolreprod.107.062018PubMedID: 17942797OAI: oai:DiVA.org:oru-3557DiVA, id: diva2:137854
Available from: 2008-12-09 Created: 2008-12-09 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Androgen receptors and endocrine disrupting substances
Open this publication in new window or tab >>Androgen receptors and endocrine disrupting substances
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Throughout the animal kingdom, organisms are dependent on substances such as steroid hormones to help them maintain internal balances. Examples of important tasks that are under regulation of steroid hormones are somatic and gonadal development, sexual performance and behavior (both social and sexual) as well as sex differentiation. Balance in the biology of reproduction is important for all organisms, and is sensitive to alterations and disturbances. If the environment is altered in a manner that lead to higher estrogenic or androgenic levels, the sex ratio of organisms that do not rely on genetic differences in the sex differentiation, will be biased towards more females or males in the population. It has been known for some time that there are pollutants in the environment that affect steroid pathways, such as the estrogenic and thyroid systems, but not much has been known about the androgenic systems. Examples of populations being masculinized have been recorded, and estrogenic compounds have been known to act as antiandrogens, but not until recently the first androgen agonist was identified. We used a combination of in vitro and computational modeling to identify the brominated flame retardant, 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane, as a potent androgen agonist to the human androgen receptor.

In addition to this we cloned and characterized the androgen receptor from, a frequently used model organism, zebrafish (Danio rerio) as a receptor primarily activated by 11-ketotestosterone. This is a feature the zebrafish share with several other teleost fishes, such as the three-spined stickleback. Thus fish androgen receptors differ from most mammalian androgen receptors, where dihydrotestosterone is the most potent activator.

 

Place, publisher, year, edition, pages
Örebro: Örebro universitet, 2010. p. 64
Series
Örebro Studies in Life Science ; 5
Keywords
Androgen receptor, Brominated flame retardant, TBECH, Endocrine disruptor
National Category
Biological Sciences Natural Sciences
Research subject
Biology
Identifiers
urn:nbn:se:oru:diva-9679 (URN)978-91-7668-714-7 (ISBN)
Public defence
2010-02-26, Hörsal P2, Örebro, 10:15 (English)
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Available from: 2010-02-10 Created: 2010-02-09 Last updated: 2017-10-18Bibliographically approved

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Larsson, AndersScherbak, NikolaiOlsson, Per-Erik

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