D-aspartic acid is a physiological amino acid occurring principally in the pituitary gland and testes and has a role in the regulation of the release and synthesis of LH and testosterone in humans and rats.

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In human follicular fluid, D-Asp is present at a relatively higher concentration in younger women than in older patients and there appears to be a relationship between the concentration of d-Asp and fertility outcome parameters. These findings suggest that follicular D-Asp concentration may be considered as an alternative or additional biochemical marker for oocyte quality in patients undergoing IVF programmes.

The D-isomer of aspartic acid (D-Asp) has been found in rat testes. In the present study, samples of testicular venous blood plasma, rete testis fluid, interstitial extracellular fluid, luminal fluid from the seminiferous tubules, testicular parenchymal cells, epididymal spermatozoa and peripheral blood plasma were collected and analyzed for D-Asp by two methods, an enzymatic and a chromatographic HPLC method. The two methods gave very similar results for all samples. The highest concentrations of D-Asp (about 120 nmol/ml) were found in testicular venous blood plasma, with slightly lower concentrations in rete testis fluid (95 nmol/ml) and epididymal spermatozoa (80 nmol/g wet weight). Lower levels were found in testicular parenchymal cells (which would comprise mostly spermatids and spermatocytes), luminal fluid from the seminiferous tubules and interstitial extracellular fluid (26, 23 and 11 nmol/ml respectively). However, these values were all higher than those for peripheral blood plasma (6 nmol/ml). It would appear that D-Asp is being secreted by the testis mostly into the venous blood, passing thence into the rete testis fluid and being incorporated into the spermatozoa at the time or after they leave the testis. The distribution of D-Asp is thus quite different from that of testosterone, and its role and the reason for its high concentration in the male reproductive tract remain to be elucidated.z 1998 Federation of European Biochemical Societies.

In this study, using an enzymatic HPLC method in combination with D-aspartate oxidase, we show that N-methyl-D-aspartate (NMDA) is present at nanomolar levels in rat nervous system and endocrine glands as a natural compound, and it is biosynthesized in vivo and in vitro. D-aspartate (D-Asp) is its natural precursor and also occurs as an endogenous compound. Among the endocrine glands, the highest quantities of D-Asp (78 +/- 12 nmol/g) and NMDA (8.4 +/- 1.2 nmol/g) occur in the adenohypophysis, whereas the hypothalamus represents the area of the nervous system where these amino acids are most abundant (55 +/- 9 and 5.6 +/- 1.1 nmol/g for D-Asp and NMDA, respectively). When D-Asp is administered to rats by ip injection, there is a significant uptake of D-Asp into the adenohypophysis and a significant increase in the concentration of NMDA in the adenohypophysis, hypothalamus and hippocampus, suggesting that D-Asp is an endogenous precursor for NMDA biosynthesis. Experiments conducted on tissue homogenates confirm that D-Asp is the precursor of the NMDA and that the enzyme catalyzing this reaction is a methyltransferase. S-adenosyl-L-methionine (SAM) is the methyl group donor. In vivo experiments consisting of ip injections of sodium D-aspartate show that this amino acid induced a significant serum PRL elevation and this effect is dose and time dependent. In vitro experiments conducted on isolated adenohypophysis or adenohypophysis coincubated with the hypothalamus, showed that the release of PRL is caused by a direct action of D-Asp on the pituitary gland and also mediated by the indirect action of NMDA on the hypothalamus. Then, the latter induces the release of a putative factor that in turn stimulates the adenohypophysis reinforcing the PRL release. In conclusion, our data suggest that D-Asp and NMDA are present endogenously in the rat and are involved in the modulation of PRL release.