NON-ACTH POMC FRAGMENTS STIMULATE ALDOSTERONE PRODUCTION BY HUMAN ADRENAL-CELLS IN-VITRO

The possibility that non-ACTH proopiomelanocortin-derived fragments ma y stimulate aldosterone production has previously been studied using n onhuman cells with inconsistent results. We have examined the response of aldosterone to P-endorphin (P-End) and joining peptide (JP) and co mpared these with the response to ACTH using eight cell suspensions pr epared 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). beta-End s ignificantly 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 beta-End did not provide significant stimulation. Furthermore, JP stimulated aldosterone biosynthesis (41 +/- 16 fmol/10(4) cells abo ve 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 beta-End to hu man adrenal cells yielded values significantly greater than those achi eved with either agent alone (268 +/- 152 and 183 +/- 89 fmol/10(4) ce lls above basal; p < 0.05). These data indicate for the first time tha t beta-End and JP have the capacity to stimulate aldosterone productio n in human adrenal cells in vitro. The physiological and potential cli nical significance of these observations has yet to be elucidated. (C) 1998 by Elsevier Science Inc.