ACTH INDUCES UP-REGULATION OF ACTH RECEPTOR MESSENGER-RNA IN MOUSE AND HUMAN ADRENOCORTICAL CELL-LINES

Corticotropin (ACTH) binds to specific receptors in the adrenal cortex and thereby regulates glucocorticoid and mineralocorticoid production . The number of ACTH binding sites on adrenocortical cells is increase d by exposure of cells to activators of the cAMP pathway. The mechanis m responsible for the increase in ACTH binding sites is not known. We therefore studied the levels of ACTH-R mRNA in mouse Y-1 and human NCI -H295 (H295) adrenocortical carcinoma cell lines. ACTH induced an incr ease in mouse ACTH-R mRNA in Y-1 cells that was time and dose dependen t, increasing 6-fold over basal revels following exposure to 10(-8) M ACTH for 19-24 h. The amount of human ACTH-R mRNA in H295 cells increa sed 2-4-fold following a 24 h exposure to 10(-8) M ACTH, 1 mM dbcAMP, or 10(-5) M Forskolin, Treatment of H295 cells with angiotensin II (A- II) was found to dramatically increase the lever of ACTH-R mRNA. These data indicate that regulation of ACTH-R mRNA levels is at least one m echanism by which ACTH and A-II elevate the number of ACTH binding sit es in the adrenocortical cell.