2002 年 30 巻 4 号 p. 204-215
After some doubt, it has now been confirmed that D-amino acids occur naturally in mammalian tissues. In this review, I describe our work with D-aspartate. Immunohistochemical staining reveals that D-aspartate is found in specific cells at distinct periods during the development of rat brain, adrenal, pineal, and pituitary glands, and testis. D-Aspartate appears to be synthesized by the pituitary gland and testis and then secreted into the vascular system which transports it to tissues such as the adrenal and pineal glands, which take it up using the L-Glu transporter. The D-aspartate synthesized by the anterior lobe of the pituitary gland may stimulate prolactin-producing cells to secrete more prolactin in an autocrine and paracrine fashion. In the testis, D-aspartate produced inside the seminiferous tubules may act in a paracrine fashion on Leydig cells that reside outside the tubules to increase their testosterone production by stimulating their expression of Steroidogenic Acute Regulatory protein gene. D-Aspartate in the pineal gland, apparently primarily derived from outside the tissue, suppresses the melatonin secretion by the parenchymal cells (pinealocytes). Studies with cultured mammalian cell lines reveal that intracellular D-aspartate concentrations appears to change during the cell cycle and can be regulated by the cell density of the culture. These studies also showed that mammalian cells contain all the molecular components needed to regulate D-aspartate homeostasis, as they can biosynthesize, release, take up, and degrade D-aspartate. D-Aspartate thus appears to function in the mammalian body as a novel type of a messenger.