d-Aspartic acid implication in the modulation of frog brain sex steroid levels

There is evidence that d-aspartate (d-Asp) modulates sex hormone levels in frog testis by regulating the activity of P450 aromatase (P450 aro), the key enzyme which converts Testosterone (T) in 17ß-Estradiol (E2). Here we report, for the first time, that there is a direct correlation among brain levels of d-Asp, P450 aro, E2 and Estradiol Receptor (ERα) in the male frogs during the reproductive as well as the post-reproductive phases of the breeding cycle, with highest levels being observed in the post-reproductive period. d-Asp i.p. administration to frogs ready for reproduction, induced an increase of brain P450 aro protein expression with concomitant enhancement of both E2 levels and ERα expression; at the same time, brain T levels and Androgen receptor expression decreased. In contrast, in the post-reproductive frogs, d-Asp treatment did not modify any of these parameters. Taken together, these results imply that the regulation of P450 aro expression by d-Asp could be an important step in the control of E2 levels in the frog brain.

► d-Asp induces an increase of brain P450 aro expression in reproductive frogs. ► Increased P450 aro expression is correlated with enhanced E2 levels and ERα expression. ► d-Asp-mediated P450 aro expression could be implicated in brain E2 level control.