The tyrosine hydroxylase gene is subject to very precise regulation which aim is to adjust the level of the catecholamines to current stimuli disturbing the homeostasis . The fine tuning of the TH gene activity is realized by the ?cross-talk? between the complexes of transcriptional factors with their appropriate regulatory sequences. The transcriptional aspect of that regulation has been reviewed emphasizing the rule of the regulatory sequences in determining cell, tissue and developmental specificity of the TH gene activity.
The tyrosine hydroxylase plays a key role in the catecholamine synthesis responding to many stimuli disturbing homeostasis. In this part we described the posttranscriptional levels of the gene and the protein regulation including: alternative splicing, isoform specificity, feedback inhibition, protein phosphorylation and dephosphorylation, protein stability, translational regulation.
Vulnerability of midbrain dopaminergic (DA) neurons in the weaver mouse was studied at postnatal (P) days 8 and 90, in chosen coronal levels throughout the anteroposterior (AP) extent of the substantia nigra pars compacta (SNc). Wild-type (+/+) and homozygous weaver (wv/wv) mice used were the offspring of pregnant dams injected in several cases with tritiated thymidine on embryonic days 11-15. DA neurons were identified for their tyrosine hydroxylase immunoreactivity. Data reveal that at P8, the frequency of both +/+ and wv/wv late-generated DA cells increases from rostral to caudal SNc. No apparent DA-cell loss was observed at P8 in the mutant genotype, irrespective of the AP level considered. However, throughout the AP, there was a significant reduction in the number of these neurons at any level in 90-day-old weavers. Comparison of P8 and P90 +/+ SNc suggests that cell death is not a major aspect in the developmental regulation of normal DA neurons, although numerical cell depletion in the postnatal development of weaver SNc probably results from the amplification of a basal cell-death process, which affected all the coronal levels studied.
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