Androgen regulated gene expression in the brain of the mouse

Abstract

Sexual brain dimorphism may be caused by the action of sexual steroids or/and sex specific gene expression independently from the influence of gonadal steroids. To test the first hypothesis we analysed the androgen regulated gene expression in different brain areas using the mouse model tfm (testicular feminization). The tfm phenotype is characterised by female external genitalia despite of a male karyotype in hemizygous mice because of a frame shift mutation in exon 1 of the androgen receptor gene (Ar). Expression of several genes encoding transcription factors, cell cycle proteins and structure proteins were analysed in mutated and wild-type mice by real-time PCR. Marked differential expression was observed for Hoxa13. Mutations of HOXA13 are causing the Hand-Foot-Genital Syndrome in humans. In cortex and rhombencephalon of the hemizygous Ar-deficient mice a 25–35 fold overexpression of Hoxa13 was detected whereas in other brain areas no significant difference between mutated and wild-type mice was observed. In the developing genital tubercle Hoxa13 is required for normal Ar expression. We suggest that in some brain areas upregulation of Hoxa13 may reflect a negative feed-back loop of Hoxa13 and Ar expression.