ABSTRACT

The sympatho-adrenal system is one of the principal effector systems maintaining homeostasis in vertebrates. This system is activated by diverse homeostatic perturbations. Once this system has been activated, it acts to minimize changes and restore the equilibrium. The adaptability of the sympatho-adrenal sysytem to diverse functional requirements is enhanced by the presence of multiple, physiologically distinct, secretory substances. In adrenal medullary cells, catecholamines (norepinephrine and epinephrine) are co-stored and co-secreted with a variety of neuropeptides (Livet, 1984; Eiden et al, 1984; Fleminger et al, 1984; Viveros et al, 1987). Thus, the physiological signals generated in the catecholaminecontaining cells of the adrenal medulla are encoded not only by the quantity of the released hormones but also by the relative composition of the secreted products. While the shortterm differential release of co-stored hormones could be accomplished by the discharge of secretory vesicles differing in hormonal composition, long-term regulation is likely to occur through selective changes in the synthesis of different hormones. The biosynthetic cascade for catecholamines contains four specific enzymes. Tyrosine hydroxylase (TH) is the first and rate-limiting enzyme in this pathway. It is indispensable for the expression of the general catecholaminergic trait. Phenylethanolamine N-methyltransferase (PNMT) catalyzes the last step which converts norepinephrine to epinephrine, and thus determines which of two major catecholaminergic phenotypes will predominate. Among the neuropeptides stored in the adrenal medulla, the most abundant are the proenkephalin (PE)-related peptides (Schultzberg et a/., 1979; Lewis et al, 1981). Their synthesis is controlled by the PE gene. The prohormone is processed within the Golgi network and secretory vesicles to form a family of smaller enkephalin-containing peptides. We have previously demonstrated

that long-term adaptations in catecholamine and PE synthesis during enhanced activities of the sympatho-adrenal system occur at the levels of TH, PNMT,( Stachowiak et al, 1985) and PE (Kanamatsu et al, 1986) genes, and are manifested as changes in their mRNA levels.