Opioidergic Control of the Pituitary-Adrenal Axis

Abstract

Several studies in animals (Bruni et al. 1977; Rivier et al. 1977) have shown that endogenous opiate-like peptides are involved in the neuroendocrine control of pituitary hormone secretion. In man, opiates have been shown to inhibit the pituitary-adrenal axis (Grossmann 1983). Thus, β-endorphin suppresses basal ACTH and Cortisol secretion (Taylor et al. 1983). Similarly, the δ-opiate receptor agonist morphine sulfate reduces baseline Cortisol concentrations (McDonald et al. 1959) and blocks the Cortisol response to surgical stress (George et al. 1974; Brandt et al. 1978). The met-enkephalin analog FK 33–824, a synthetic derivative acting at μ-and δ-opiate receptor sites (Kream and Zukin 1979) completely blocks the ACTH response to lysine-vasopressin (del Pozo et al. 1980). Recently it has been reported that the racemic benzomorphan κ-agonist MR 2033 also decreases ACTH and Cortisol secretion (Pfeiffer et al. 1986). Thus, there is evidence that the inhibitory action of opiates on the pituitary-adrenal axis involves μ-, δ-, and κ-binding sites. However, the physiological role and the site of action of endogenous and exogenous opioids remain to be elucidated. In recent years we have therefore studied the effect of FK 33–824, oral morphine, and naloxone on baseline and releasing hormone-stimulated ACTH and Cortisol concentrations in patients with Addison’s disease and normal subjects.