Evidence for two differentially regulated populations of peripheral β-endorphin-releasing cells in humans

In the current study we tested the hypothesis that human plasma β-endorphin (βE) is derived from at least two subpopulations of βE-releasing cells: one sensitive to glucocorticoids as well as to dopamine (DA; regulated analogously to the corticotrophs of the rat pituitary), and one insensitive to glucocorticoids but sensitive to DA (regulated analogously to the melanotrophs of the rat pituitary). To test this hypothesis, human plasma levels of ACTH, cortisol, and βE-like immunoreactivity were measured at baseline and after haloperidol treatment (0.05 mg/kg, iv) in two experimental groups, one pretreated with dexamethasone (1.5 mg) and one pretreated with placebo. Plasma PRL levels were also measured in both groups as an indicator of DA receptor blockade. Dexamethasone partially suppressed both baseline and haloperidol-stimulated levels of human plasma βE-like immunoreactivity, whereas it completely suppressed both basal and haloperidol-stimulated levels of ACTH and cortisol and had no statistically significant effect on either basal or haloperidol-stimulated PRL levels. These data support a negative feedback effect of glucocorticoids on one DA-sensitive cell population that releases both ACTH and βE (corticotroph like), but not on a second cell population that releases βE but not ACTH.