Zebrafish androgen receptor : isolation, molecular, and biochemical characterization

• 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.

Ämnesord

NATURVETENSKAP  -- Biologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences (hsv//eng)

Nyckelord

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

NATURAL SCIENCES

NATURVETENSKAP

Biology

Biologi

Biology

Biologi

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)