Substitution of synthetic chimpanzee androgen receptor for human androgen receptor in competitive binding and transcriptional activation assays for EDC screening

• Published in: Toxicology letters Vol. 174; no. 1; pp. 89 - 97
• Main Authors: Hartig, P.C., Cardon, M.C., Lambright, C.R., Bobseine, K.L., Gray, L.E., Wilson, V.S.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 01-11-2007; Amsterdam Elsevier Science
• Subjects: Adenoviridae - genetics; Adenovirus; Androgen; Androgens - metabolism; Animals; Baculoviridae - genetics; Baculovirus; Binding, Competitive; Biological and medical sciences; Biological Assay; Cell Line; Cell Nucleus - metabolism; Cercopithecus aethiops; Chimpanzee; COS Cells; Endocrine Disruptors - metabolism; Genetic Vectors; Human; Humans; Medical sciences; Metribolone - metabolism; Pan troglodytes; Plasmids; Receptor; Receptors, Androgen - genetics; Receptors, Androgen - metabolism; Recombinant Proteins - metabolism; Toxicology; Transcriptional Activation; Transduction, Genetic; Human; Androgen; Baculovirus; Adenovirus; Receptor; Chimpanzee; Competition; Adenoviridae; Transcription; Activation; Medical screening; Virus; Screening; Synthetic product; Baculoviridae; Substitution; Androgen receptor; Sex steroid hormone; Biological receptor; Hormonal receptor
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/j.toxlet.2007.08.013

The potential effect of receptor-mediated endocrine modulators across species is of increasing concern. In attempts to address these concerns, we are developing androgen and estrogen receptor binding assays using recombinant hormone receptors from a number of species across different vertebrate classes. The United States Environmental Protection Agency (USEPA) Office of Science Coordination and Policy (OSCP) requested that we develop a nonhuman mammalian receptor-binding assay for possible use in their Endocrine Disruptor Screening Program (EDSP). Since the chimpanzee androgen receptor is very similar to that of humans and thus possesses properties which could be exploited in future endocrine studies, we synthesized and expressed this gene in eukaryotic expression plasmids, baculovirus expression vectors and replication deficient adenovirus. In all ligand-binding and transcriptional activation assays tested, the chimpanzee receptor performed essentially identically to the human receptor. This suggests that the chimpanzee gene could substitute for the human gene in endocrine screening assays.