Mechanisms of Hormone Action

Zebrafish Androgen Receptor: Isolation, Molecular, and Biochemical Characterization

Abstract
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 super family. Here, we report 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 hours post fertilization and the expression level increased substantially afterwards. When analyzed during gonad development the expression level of ar mRNA at 4 weeks post 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 modelling with in vitro experiments to show that the zebrafish Ar is preferentially activated by 11-ketotestosterone.

Key words: Testis • Androgen receptor • Steroid hormones • 11-ketotestosterone • gonad differentiation

This article has been cited by other articles:

				P P de Waal, D S Wang, W A Nijenhuis, R W Schulz, and J Bogerd Functional characterization and expression analysis of the androgen receptor in zebrafish (Danio rerio) testis Reproduction, August 1, 2008; 136(2): 225 - 234. [Abstract] [Full Text] [PDF]