Tryptophan degradation by indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) in murin concepti *
Indoleamine 2, 3-dioxygenase (IDO) and tryptophan 2, 3-dioxygenase (TDO) are the tryptophan (Trp) degradation enzymes that catalyze the oxygenation of an essential amino acid, Trp, into N-formylkynurenine. In 1998, David Munn et al reported that IDO initiated Trp degradation in the placenta and that it might play an important role in the prevention of allogeneic fetus rejection by maternal T cells. However, the role of IDO has not been fully elucidated. The expression patterns of Trp degradation activity, IDO protein and IDO mRNA were examined in embryonic and extraembryonic mouse tissue. Although Trp degradation activity was very low at 5. 5 days post-coitus (dpc), it dramatically increased to the peak level at 6. 5 dpc, and then gradually decreased to the zero level by 18. 5 dpc. IDO protein, however, was detected between 8. 5 and 12. 5 dpc. IDO mRNA was also very low before 8. 5 dpc, reaching its highest peak at 9. 5 dpc. These results suggest that IDO does not contribute to the early phase of Trp degradation in gestation. IDO mRNA and protein were not expressed during such early gestation. On the other hand , TDO mRNA and protein were strongly expressed during the early gestation period. The Trp degradation activity of the early gestation period was not inhibited by a specific IDO inhibitor, 1-methyl-Trp, but that at 12. 5 dpc was strongly inhibited. These findings suggest that the Trp degradation activity of the early period is not caused by IDO, but by TDO. TDO has been reported to be localized exclusively in the adult liver. This is the first report in which extra-hepatic expression of TDO has been clearly demonstrated. These results suggest that TDO, rather than IDO, functions in Trp deprivation in early concepti to maintain nidation, and that shortly induced IDO functions in local Trp deprivation to prevent allogeneic fetus rejection, while allowing supplement of Trp to the fetus in middle phase conception. (Accepted on November 19, 2001) Kawasaki Igakkaishi 28(1) : 1-9 , 2002
