Catecholamine Synthesis is Mediated by Tyrosinase in the Absence of Tyrosine Hydroxylase

Transverse section through the thoracic region containing the paravertebral sympathetic ganglia. Transverse sections of fetal sympathetic ganglia (arrows) treated with glyoxylic acid revealed catecholamine fluorescence in the wild-type fetus (left), whereas histofluorescence was undetectable in the mutant (right). A, Aorta.

Catecholamine histofluorescence in peripheral tissues of rescued pigmented and albino TH-deficient mice. Adrenal medullae from P6 mice (a, b,c). Adrenal chromaffin cells of pigmented wild-type mice (a) possess intense catecholamine fluorescence. Adrenal chromaffin cells of pigmented TH-null mice (b) contain catecholamines, but the fluorescence is less intense than that of wild-type mice. In contrast, adrenal chromaffin cells of albino TH-null mice (c) are almost devoid of catecholamine histofluorescence. The medullary region with sparse granular fluorescence is distinguishable from the surrounding cortex by the lipid inclusions in the cortical cells. Most sympathetic SCG neurons in pigmented P6 wild-type mice (d) contain bright granular fluorescence. Principal sympathetic neurons of pigmented P6 TH-nulls (e) lacked catecholamine fluorescence; however, fluorescence was seen in SIF cells (arrow). No catecholamine fluorescence could be detected in SCG from TH-nulls that were also tyrosinase-deficient (f). Brightly fluorescent sympathetic fibers were present in the ventricular smooth muscle wall in pigmented P6 wild-type mice (g). A reduced number of brightly fluorescent fibers (arrow) were present in the ventricles of pigmented P6 TH-null mice (h). No catecholamine fluorescent fibers could be detected in the ventricles of albino TH-null mice (i). Brightly fluorescent sympathetic fibers were associated with piloerectors in the hairy skin of pigmented P6 wild-type mice (j). Fibers exhibiting intermediate or weak fluorescence were present in pigmented P6 TH-null mice (k). No catecholamine histofluorescent fibers were detected in the hairy skin of albino TH-null mice (l).

Catecholamine histofluorescence in the striata and ventral midbrains of rescued pigmented TH-null P6 pups. Coronal sections of the rostral striatum from heterozygous P6 pups (A) revealed clusters of brightly fluorescent nigral fibers, the dopamine islands (arrows). In contrast, glyoxylic acid treatment of coronal sections of rostral striatum from a pigmented TH-null littermate (B) revealed very few clusters of fluorescent fibers. Those detected were weakly fluorescent (arrow). In heterozygous pups, brightly fluorescent cells in ventral midbrain (C) were abundant in the dopamine-containing substantia nigra, pars compacta. In contrast, the substantia nigra of pigmented TH-null pups (D) contained few catecholamine fluorescent cells. Although such cells were rare, they were brightly fluorescent (arrow). c, Cortex.

Glyoxylic acid-induced catecholamine fluorescence in the striata and midbrains of albino (tyrosinase-deficient) wild-type and TH-null P6 pups. Striata from wild-type albino mice (A) contain clustered brightly fluorescent fibers, representing dopamine islands (arrows). No catecholamine histofluorescence was seen in the striata of albino TH-deficient mice (B). In the wild-type albino midbrain (C), many fluorescent dopamine cells can be observed. In contrast, no catecholamine histofluorescence could be detected in the midbrains of TH-null mice also deficient in tyrosinase (D). c, Cortex.