Dissecting the role of Androgen receptor in the central nervous system.

Androgen Receptor (AR) is a steroid hormone-activated transcription factor located in the cytoplasm in an inactive state. In response to androgen binding, AR shuttles from the cytosol to the nucleus, where it regulates the expression of specific AR target genes. AR is widely expressed throughout the brain, hippocampus, hypothalamic nuclei (like the preoptic area, POA), and amygdala.

Of note, these brain areas hold sexually dimorphic characteristics, which are translated in sex-typed behaviour, including aggression, parental care, mating, and anxiety. AR gene is located in the X chromosome; therefore, it is present in a single copy in men. Males lacking or expressing mutant AR display female-like external sexual organs and infertility, which are recapitulated in rodent models of androgen insensitivity syndrome. Many studies have been focused on understanding the role of AR in male phenotype. However, the AR-driven molecular mechanisms leading to sexually dimorphic brain and behaviours are still largely unknown. In the nucleus, AR can regulate the expression of its target genes by recognizing and binding specific DNA sequences, termed androgen response elements (ARE), in their promoter and enhancer regions. Our data suggest that AR is able to change its subcellular localization in response to androgens and neuronal activity, ultimately modulating the expression of immediate-early and late-response downstream target genes.

Our findings suggest a new role for AR as activity-dependent transcription factor. We are further investigating AR role in the CNS by dissecting the molecular changes driven by AR in one of the typical male behaviours known to be governed by androgens and AR, which is the male mating behaviour.