Regional and sex-related differences in modulating effects of female sex steroids on ecto-5′-nucleotidase expression in the rat cerebral cortex and hippocampus

Abstract

Ecto-5′-nucleotidase (eN), a membrane rate-limiting enzyme of the purine catabolic pathway, catalyzes the conversion of AMP to adenosine involved in the regulation of many brain physiological and pathological processes. Since gender fundamentally determines hormonal milieu in the body and brain, it is reasonable to assume that sex differences in the activity of various signaling systems, including adenosine, may be generated by gonadal steroids. Thus, we examined expression of eN as a component of adenosine signaling system in the basal state in cerebral cortex and hippocampus of male and female rats at gene, protein and functional level, as well as in the state of gonadal hormone deprivation, induced by ovariectomy (OVX), whereas impact of steroid hormones was explored after repeated administration of 17α-estradiol, 17β-estradiol and progesterone for seven consecutive days. Results showed regional and sex-related differences in basal eN activity level, with the highest AMP hydrolysis observed in the hippocampus of male rats. Furthermore, ovarian steroids do not contribute to basal gene eN expression or the activity in cortical and hippocampal region of female rats. However, protein eN expression was increased in OVX rats in both investigated region. Investigated exogenous steroids had no influence on eN expression in male brain, while in OVX females alterations in eN activity were induced. The observed effects in female rats were different between examined regions e.g. in cortex, applied treatments predominantly decreased whereas in hippocampus increased eN activity. Based on the presented results, eN exerts regional and sex-related response in basal state as well as after treatment with female gonadal hormones, however the exact mechanisms of sex steroids actions on eN remain unclear and should be fully explored.