We propose to continue our ongoing studies into the genetic control of the catecholamine biosynthetic enzymes in adrenal glands of inbred mouse strains. Our previous data showed that each of the three enzymes was under control of a single major gene locus, and that a single regulatory gene appeared to control the phenotypic expression of the entire pathway. Studies into the biochemical mechanism of gene control showed that, for one of the enzymes, the gene controlled the rate of degradation of the enzyme. Studies on the synthesis and degradation rates of the other two enzymes are currently ongoing. For a second enzyme, our data is compatible with an altered rate of degradation as well, although differences in the rate of synthesis have also been found. Our operating hypothesis is that the gene which controls expression of the three enzymes codes for a degrading enzyme, and that the three catecholamine synthetic enzymes are substrates for this protease. During the current funding period, we plan to finish our studies on the secod enzyme (dopamine B-hydroxylase) and begin studies on the degradation of tyrosine hydroxylase. BIBLIOGRAPHIC REFERENCES: Ciaranello,R.D., Hoffman,H., Shire, J.G.M. and Axelrod, J. Genetic regulation of the catecholamine biosynthetic enzymes. II. Inheritance of tyrosine hydroxylase, dopamine B-hydroxylase and phenylethanolamine N-methyltransferase. J. Biol.Chem. 249:4528-4534, 1974. Ciaranello, R.D., Wooten, G.F. and Axelrod, J. Regulation of dopamine B-hydroxylase in rat adrenal glands. J. Biol. Chem. 250:3204-3211, 1975.