Glucocorticoids regulate adrenal opiate peptides

Although glucocorticoids and impulse activity are well-recognized mediators of adrenal catecholamine biosynthesis, the effects of these signals on the colocalized opiate peptide system is only presently emerging. Since it is generally agreed that impulse activity regulates adrenal opiate peptides, in the present report we sought to determine whether adrenal opiates are also subject to hormonal control. Pharmacological destruction of the adrenal cortex resulted in a decrease in baseline Leu-enkephalin levels in vivo. This suggested a tonic regulatory effect of adrenal cortical steroids on enkephalin pathways. To further examine the role of glucocorticoid hormones in regulating enkephalin biosynthesis in a more dynamic system, medullae were grown as explants where peptide levels typically rise 30- to 50-fold above baseline. Explanted medullae required medium supplemented with dexamethasone or corticosterone to achieve maximal levels of Leu-enkephalin in a dose-dependent fashion. The effects of glucocorticoid treatment were blocked by specific glucocorticoid receptor antagonists or by inhibition of receptor translocation to the nucleus. Since enkephalin levels rose in cultured medullae (even in the absence of added glucocorticoids), glucocorticoid-independent regulatory mechanisms may also play a role in this model. Based on this and previous results, it appears that adrenal opiate peptides, like catecholamines, are subject to dual hormonal and transsynaptic regulatory influences. The interaction of these two regulatory mechanisms may serve an adaptive role in modulating complex biochemical and behavioral responses with exquisite precision.