Non-ACTH POMC fragments stimulate aldosterone production by human adrenal cells in vitro

The possibility that non-ACTH proopiomelanocortin-derived fragments may stimulate aldosterone production has previously been studied using nonhuman cells with inconsistent results. We have examined the response of aldosterone to β-endorphin (β-End) and joining peptide (JP) and compared these with the response to ACTH using eight cell suspensions prepared from human adrenal glands. ACTH, 10 −6, 10 −8, and 10 −10 M, consistently stimulated aldosterone accumulation above that occurring in unstimulated cells (150 ± 83, 120 ± 62, and 77 ± 32 fmol/10 4 cells above basal, respectively; mean ± SE; p < 0.05). β-End significantly stimulated aldosterone production at 10 −6 and 10 −8 M (114 ± 84 and 50 ± 24 fmol/10 4 cells above basal; p < 0.05); 10 −10 M β-End did not provide significant stimulation. Furthermore, JP stimulated aldosterone biosynthesis (41 ± 16 fmol/10 4 cells above basal; p < 0.05), only at the highest concentration used, 10 −6 M. The addition of 10 −8 M ACTH plus 10 −6 and 10 −10 M β-End to human adrenal cells yielded values significantly greater than those achieved with either agent alone (268 ± 152 and 183 ± 89 fmol/10 4 cells above basal; p < 0.05). These data indicate for the first time that β-End and JP have the capacity to stimulate aldosterone production in human adrenal cells in vitro. The physiological and potential clinical significance of these observations has yet to be elucidated.