title: Induced synthesis of P450 aromatase and 17β-estradiol by D-aspartate in frog brain.
abstract: D-Aspartic acid is an endogenous amino acid occurring in the endocrine glands as well as in the nervous system of various animal phyla. Our previous studies have provided evidence that D-aspartate plays a role in the 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 and irreversibly converts testosterone into 17β-estradiol. In this study, we firstly investigated the immunolocalisation of P450 aromatase in the brain of P. esculentus, which has never previously been described in amphibians. Therefore, to test the hypothesis that d-aspartate mediates a local synthesis of P450 aromatase in the frog brain, we administered D-aspartate in vivo to male frogs and then assessed brain aromatase expression, sex hormone levels and sex hormone receptor expression. We found that D-aspartate enhances brain aromatase expression (mRNA and protein) through the CREB pathway. Then, P450 aromatase induces 17β-estradiol production from testosterone, with a 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 regulation of the reproductive axis. Accordingly, we found that the sites of P450 aromatase immunoreactivity in the frog brain correspond to the areas known to be involved in neurosteroid synthesis.
authors: Dipartimento di Scienze della Vita, Seconda Università degli Studi di Napoli, Via Vivaldi 43, 81100, Caserta,  Italy.
authors: Lavinia
authors: L
authors: Burrone
authors: Alessandra
authors: A
authors: Santillo
authors: Claudia
authors: C
authors: Pinelli
authors: Gabriella Chieffi
authors: GC
authors: Baccari
authors: Maria Maddalena
authors: MM
authors: Di Fiore
mesh_terms: D029845:Amphibian Proteins / Q000096:biosynthesis*; D000818:Animals; D001001:Anura; D001141:Aromatase / Q000096:biosynthesis* / Q000235:genetics; D001921:Brain / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D026603:D-Aspartic Acid / Q000378:metabolism* / Q000494:pharmacology; D004958:Estradiol / Q000096:biosynthesis*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000096:biosynthesis*; D013739:Testosterone / Q000378:metabolism*
chemical_list: D029845:Amphibian Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D013739:Testosterone; D026603:D-Aspartic Acid; D004958:Estradiol; D001141:Aromatase