Induced synthesis of P450 Aromatase and 17β-estradiol by D-aspartate in frog brain

Abstract

Summary D-aspartic acid is an endogenous amino acid occurring in endocrine glands as well as in nervous system of various animal phyla. Our previous studies have provided evidence that D-Aspartate plays a role in induction of estradiol synthesis in gonads. Recently, we have also demonstrated that D-aspartic acid induces P450 aromatase mRNA expression in the frog (Pelophylax esculentus) testis. P450 aromatase is the key enzyme in the estrogen synthetic pathway, which irreversibly converts testosterone into 17β-estradiol. In this study, we firstly investigated the immunolocalisation of P450 aromatase in the frog brain P. esculentus, never described in amphibians. Therefore, to test the hypothesis that D-Aspartate mediates a local synthesis of P450 aromatase in the frog brain, we administered in vivo D-Aspartate to frog male and then assessed the brain aromatase expression, sex hormone levels as well as their receptor expressions. We found that D-Aspartate enhances brain aromatase expression (mRNA and protein) through CREB pathway. Then, P450 aromatase enzyme induces 17β-estradiol production from testosterone, with consequent increase of its receptor. Therefore, the regulation of D-Aspartate-mediated P450 aromatase expression could be an important step in the control of neuroendocrine regulations of the reproductive axis. On the other hand, we found that the sites of P450 aromatase immunoreactivity in the frog brain correspond to the areas known to be involved in neurosteroid synthesis.