Occurrence of D-aspartic acid and N-methyl-D-aspartic acid in rat neuroendocrine tissues and their role in the modulation of luteinizing hormone and growth hormone release

Using two specific and sensitive fluorometric/HPLC methods and a GC-MS meth od, alone and in combination with D-aspartate oxidase, we have demonstrated for the first time that N-methyl-D-aspartate (NMDA), in addition to D-aspa rtate (D-Asp), is endogenously present as a natural molecule in rat nervous system and endocrine glands. Both of these amino acids are mostly concentr ated at nmol/g levels in the adenohypophysis, hypothalamus, brain, and test is. The adenohypophysis maximally showed the ability to accumulate D-Asp wh en the latter is exogenously administered. In vivo experiments, consisting of the i.p. injection of D-Asp, showed that D-Asp induced both growth hormo ne and luteinizing hormone (LH) release. However, in vitro experiments show ed that D-Asp was able to induce LH release from adenohypophysis only when this gland was co-incubated with the hypothalamus. This is because D-Asp al so induces the release of GnRH from the hypothalamus, which in turn is dire ctly responsible for the D-Asp-induced LH secretion from the pituitary glan d. Compared to D-Asp, NMDA elicits its hormone release action at concentrat ions similar to 100-fold lower than D-Asp. D-AP5, a specific NMDA receptor antagonist, inhibited D-Asp and NMDA hormonal activity, demonstrating that these actions are mediated by NMDA receptors. NMDA is biosynthesized from D -Asp by an S-adeno- sylmethionine-dependent enzyme, which we tentatively de nominated as NMDA synthase.-D'Aniello, A., Di Fiore, M. M., Fisher, G. H., Milone, A., Seleni, A., D'Aniello, S., Perna, A. F., Ingrosso, D. Occurrenc e of D-aspartic acid and N-methyl-D-aspartic acid in rat neuroendocrine tis sues and their role in the modulation of luteinizing hormone and growth hor mone release.