Specific localization of the guanosine triphosphate (GTP) cyclohydrolase I-immunoreactivity in the human brain

Guanosine triphosphate (GTP) cyclohydrolase I (GCH) is the first and rate-l imiting enzyme for biosynthesis of tetrahydrobiopterin, the cofactor of tyr osine hydroxylase (TH). Our previous study reported the presence of GCH in several neuronal groups in animal brains using a newly raised anti-GCH anti body. The present study aims at elucidating whether GCH and TH coexist in t he same neurons of the human brain with the aid of immunohistochemical dual labeling. GCH-immunoreactivity was observed in the cell bodies and fibers of monoaminergic neurons of the human brain. Neurons which contain both enz ymes are seen in the human substantia nigra, ventral tegmental area, locus coeruleus, dorsal raphe, and zona incerta. In these regions, almost all the cells also show immunoreactivity for aromatic L-amino acid decarboxylase ( AADC), the second step enzyme for catecholamine synthesis, indicating that these neurons are catecholaminergic. However, some neurons in the dorsal an d dorsomedial hypothalamic nuclei are stained only for GCH or TH. They appe ar to constitute an independent cell group in the human brain. The present observation suggests that L-dopa is not produced in the cells immunoreactiv e for TH but not for GCH, and that TH in these cells which lack GCH may hav e an unidentified role other than dopa synthesis.