Molecular Adaptations in Catecholamine Biosynthesis Induced by Cold Stress and Sympathectomy

Chronic cold stress and chemical sympathectomy are known to increase the synthesis and release of catecholamines in the adrenal medulla. Chromaffin cells adapt to altered functional requirements by increasing the synthesis of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis. In this study, we investigated the molecular genetic mechanisms underlying these changes in enzyme activity. Estimates of TH mRNA levels were obtained by RNA dot-blot analysis with a cloned TH cDNA hybridization probe. Exposure to cold produced a 4.3-fold increase in the relative abundance of adrenomedullary TH mRNA. Increases in TH mRNA levels (90%) also were observed in the brainstem of cold-stressed animals. The relative amount of TH synthesized in vitro in a rabbit reticulocyte cell-free system, programmed with adrenal poly(A)+RNA, increased 4.3 times in cold-stressed rats. Alteration in TH mRNA abundance appears to be specific, as we observed no significant difference in the levels of total RNA or poly(A)+RNA in this tissue. In addition, the relative abundance of adrenomedullary TH mRNA increased by 60% 4 days after systemic administration of the neurotoxin 6-hydroxydopamine. This increase was transient and disappeared 2 weeks after the lesion. Changes in TH mRNA levels after cold stress or sympathectomy were eliminated by denervation of the adrenal gland. These results indicate that alterations in the relative abundance of TH mRNA mediate changes in TH activity induced by chronic stress or sympathectomy, and that these changes require an intact sympathetic input.