Copper deficiency alters rat dopamine beta-monooxygenase mRNA and activity

Dopamine P-monooxygenase (DBM), a cuproenzyme, converts dopamine to norepin ephrine in selected cells. Studies were conducted in albino rats to resolve the known paradox of DBM after copper deficiency in which metabolite analy ses of tissues suggest lower activity, whereas direct assay of homogenates suggests enhanced activity. After 4 wk of postweanling copper deficiency, m ale Holtzman rats exhibited 1.4-fold higher adrenal DBM activity and 1.8-fo ld higher adrenal DBM mRNA levels than copper-adequate rats. Mixing experim ents did not support the existence of endogenous activators or inhibitors. Adrenal catecholamine content indicated lower norepinephrine, higher dopami ne and unaffected epinephrine content in copper-deficient compared with cop per-adequate rats. Studies in 22-d-old male Sprague-Dawley offspring of dam s started on copper deficiency at d 7 of gestation indicated similar result s for adrenal DBM mRNA, a 1.75-fold increase compared with copper-adequate pups. Adrenal dopamine content was higher in female copper-deficient offspr ing compared with controls, but norepinephrine was not lower. Medulla oblon gata/pons DBM mRNA concentration was higher in 22-d-old copper-deficient fe male but not male rats compared with controls. Six weeks of copper repletio n to the 22-d-old rats restored adrenal DBM mRNA levels to control values. Enzyme assay and RNA results are consistent with enhanced formation of DBM in adrenal gland and noradrenergic cell bodies of copper-deficient rats. Th e molecular signal may not be solely lower norepinephrine content because a drenal DBM mRNA changes were evident in both nutritional models, whereas th e norepinephrine content was altered only in the postnatal model.