Androgen receptors in Purkinje neurons are modulated by systemic testosterone and sexual training in a region-specific manner in the male rat

Abstract

The androgen receptor (AR) is a widely distributed molecule indicating the spread actions of its ligand steroid, and plays an important role underlying male sexual behavior. Nevertheless, the influence of steroid hormones and their receptors on cerebellar neurons, as foundation of sexual behavior, is largely unknown. We sought to determine the influence of peripheral hormones on the AR expression in Purkinje neurons across cerebellar lobules in the vermis of male rats. First, we found a basal AR expression in Purkinje neurons that was higher in the superficial region than the deep region only in cerebellar lobules 2, 4, 5, 7, 8 and 9. Moreover, only the cerebellar lobule 10 showed a significant difference between the coordinates 0.1, 0.3 and 0.9. Second, males with four sessions of sexual training showed a decreased AR density in cerebellar lobules 7, 8, 9 and 10, but not in lobules 2, 4 or 5 when compared to males with one session of sexual training. However, sexual training did not affect AR expression in Purkinje neurons according to their location in any of the cerebellar lobules studied. Third, castration decreased the AR density in the cerebellar lobules 1, 2, 5 and 9 in the superficial region, while in the deep region all cerebellar lobules, except lobule 6, showed a lower AR density after castration. Finally, testosterone replacement restored AR density to control levels in all cerebellar lobules in the superficial region that were affected by castration. Contrary, in the deep region hormonal replacement failed to restore the AR density to control level in the majority of the cerebellar lobules that were affected by castration. Altogether, our findings indicate that Purkinje neurons in the vermis are influenced by systemic testosterone in a region-dependent manner highlighting a link between the cerebellum and gonads in the male rat. The AR function in Purkinje neurons may be related to cerebellar plasticity since both estrogen and progesterone receptors, members of the nuclear receptor family, regulate plasticity processes in Purkinje neurons. We concluded the cerebellum is an important component of the neural circuit for male sexual behavior.

Keywords: Androgen receptor; Castration; Cerebellar lobules; Purkinje neuron; Sexual behavior; Vermis.