The Role of Dopaminergic Neurons in the Regulation of Pituitary Beta-endorphin Secretion

At the time this study was initiated, virtually nothing was known about neural mechanisms controlling pituitary secretion of the opiate peptide, beta-endorphin. The purpose of the present investigation was to determine the extent to which brain dopamine neurons regulate beta-endorphin secretion from the anterior and intermediate lobes of the pituitary gland. Adult male rats or primary pituitary cell cultures were treated with dopaminergic agonists, antagonists, combinations of the two or appropriate vehicles. Total immunoreactive beta-endorphin and the major molecular forms of circulating immunoreactive beta-endorphin beta-lipotropin- and beta-endorphin-sized immunoreactivity were evaluated by radioimmunoassay in conjunction with gel filtration chromatography. The results demonstrate that dopamine differentially controls beta-endorphin secretion from both the anterior and intermediate lobes by its effects on dopamine-1 and dopamine-2 receptor subtypes. Mixed dopaminergic agonists and selective dopamine-2, but not dopamine- 1, agonists increased plasma levels of total immunoreactive beta-endorphin in a time- and dose-related fashion. These apparent dopamine-2-mediated increases were due to elevated beta-lipotropin-sized immunoreactivity, material secreted exclusively by the anterior lobe. Conversely, beta-endorphin-sized immunoreactivity, which primarily reflects intermediate lobe secretion, was moderately reduced. The dopamine agonist-evoked release was prevented either by dopamine-2 receptor blockade or by glucocorticoid pretreatment which inhibits anterior but not intermediate lobe secretion of immunoreactive beta-endorphin. Since dopamine agonists had no direct effect on secretion of immunoreactive beta-endorphin from anterior lobe cultures, a dopamine-2 receptor mechanism within the brain probably enhances the release of hypothalamic corticotropin releasing factor.