Comparison of brainstem and adrenal circadian patterns of epinephrine synthesis

The enzyme which converts to norepinephrine to epinephrine, phenylethanolamine N-methyltransferase (PNMT), is found in brain as well as in the adrenal medulla. PNMT activity is subject to regulation by glucocorticoids, hormones which have a diurnal rhythm. We asked (1) whether a diurnal fluctuation exists in adrenal and brain PNMT activity and (2) what relationship this fluctuation might have to the diurnal rhythm in circulating glucocorticoids. Rats were sacrificed at 4-hour intervals over a 24-hour period. The PNMT activity in the adrenals and brainstems of these animals was determined by radioenzymatic assay, and the plasma levels of corticosterone were measured by competitive protein binding. No significant temporal variation was found in adrenal PNMT activity. Brainstem PNMT activity, however, showed a distinct diurnal fluctuation in activity, with a nadir at 7 a.m. and a peak at 3 p.m. The rise in brainstems PNMT clearly preceded by several hours the circadian rise in plasma corticosterone. We conclude that the circadian rhythm in circulating corticosterone does not drive the diurnal variation in brain PNMT activity. In unstressed animals, injection of exogenous corticosterone failed to elevate brainstem PNMT activity, whereas injection of specific inhibitors of PNMT activity significantly elevated plasma corticosterone levels. These data raise the possibility that the converse is true: changes in epinephrine synthesis may modulate the diurnal rhythm in pituitary-adrenal activity.