EXPRESSION OF TYROSINE-HYDROXYLASE GENE IN CULTURED HYPOTHALAMIC CELLS - ROLES OF PROTEIN-KINASE-A AND PROTEIN-KINASE-C

In hypothalamic cells cultured in serum-free medium, the quantity of t yrosine hydroxylase mRNA increases after treatment with an activator o f the protein kinase A pathway (8-bromoadenosine cyclic AMP, 3-isobuty l-1-methylxanthine, or forskolin) or an activator of protein kinase C (12-O-tetradecanoylphorbol 13-acetate or sn-l,2-diacylglycerol). The t yrosine hydroxylase mRNA level decreases in the cells after inhibition of protein kinase C with calphostin C or after depletion of protein k inase C by extended phorbol ester treatment. These data suggest that b oth protein kinase pathways regulate tyrosine hydroxylase gene express ion in hypothalamic cells. As simultaneous activation of both pathways has less than an additive effect on the tyrosine hydroxylase mRNA lev el, they appear to be interrelated. Compared with the rapid and dramat ic increase of the tyrosine hydroxylase mRNA level in pheochromocytoma cells, activation of the protein kinase A or protein kinase C pathway in the cultured hypothalamic cells induces slow changes of a small ma gnitude in the amount of tyrosine hydroxylase mRNA. The slow regulatio n of tyrosine hydroxylase gene expression in hypothalamic dopaminergic neurons corresponds to the relatively high stability of-tyrosine hydr oxylase mRNA (half-life=14+/-1 h) in these cells.