Neural and humoral factors separately regulate neuropeptide Y, enkephalin, and chromogranin A and B mRNA levels in rat adrenal medulla.

The influence of neurogenic versus humoral factors on mRNA levels of several secretory proteins of rat adrenal medulla was studied in vivo. Increased splanchnic nerve activity was generated (reflexly) with insulin treatment. Twenty-four hours after insulin injection, levels of mRNAs encoding neuropeptides (enkephalin and neuropeptide Y) were increased 6.5-fold, whereas those of mRNAs for the major secretory proteins (chromogranins A and B) were unchanged. Bilateral transection of the splanchnic nerves completely prevented this increase. Hypophysectomy decreased levels of chromogranin A mRNA to 32% of control, suggesting a dependence on hormones of the pituitary-adrenal axis. Treatment of hypophysectomized rats with dexamethasone restored chromogranin A mRNA to basal levels. Chromogranin B mRNA levels were not changed by either insulin treatment or hypophysectomy. These results demonstrate (i) that different classes of secretory proteins present in chromaffin granules are regulated by different mechanisms, (ii) that this regulation occurs at a pretranslational site, and (iii) that the relative concentration of secretory constituents of chromaffin granules may vary. The significance of an altered composition of secretory-granule constituents, which may be important in hypotension or stress, is discussed.