Feedback Inhibition of Tyrosine Hydroxylase from Five Regions of Rat Brain by 2-Hydroxyestradiol and Dihy droxy pheny lalanine

Abstract: Inhibition of tyrosine hydroxylase from five regions of rat brain by a model catecholamine, DOPA and a model catecholestrogen, 2-hydroxyestradiol, was examined. Tyrosine hydroxylase preparations from amygdala, preoptic, hypothalamic, striatal and hippocampal regions were freed of small molecules by gel filtration before use. The feedback inhibition of tyrosine hydroxylase by the two model catechols was studied using a spectrum of reduced pterin cofactors, including tetrahydrobiopterin, 6-methyl-tetrahydropterin and 6, 7-dimethyltetrahydropterin. Micromolar levels of either inhibitor produced marked inhibition of tyrosine hydroxylase from all regions when subsaturating levels of the endogenous cofactor, tetrahydrobiopterin, were used.