Reduced androgen receptor gene expression with first exon CAG repeat expansion

• DOI: 10.1210/me.10.12.1527
• Publication Date: 2004-02-23T18:40:41Z
• Authors: C. S. Choong
• Keywords: 0303 health sciences; 03 medical and health sciences

The molecular basis for partial androgen insensitivity associated with adult onset spinal/bulbar muscular atrophy was investigated by transient transfection of human receptor (AR) expression vectors containing increasing CAG repeat lengths in the first exon. An inverse relationship observed between length and AR mRNA protein levels. Trinucleotide 43 65 decreased levels but did not alter equilibrium binding affinity [3H]R1881 or inherent transcriptional activity AR, expressed as androgen-dependent fold induction a mouse mammary tumor virus promoter-luciferase reporter vector. findings indicate that glutamine expansion up to 66 residues NH2-terminal domain does functional activity. Rather, region exon reduces expression. study reveals previously unrecognized effect on novel mechanism resistance.