REGULATION OF ACTH RECEPTOR MESSENGER-RNA AND BINDING-SITES BY ACTH AND ANGIOTENSIN-II IN CULTURED HUMAN AND BOVINE ADRENAL, FASCICULATA CELLS

Human (HAC) and bovine (BAG) adrenal fasciculata cells express ACTH an d angiotensin-II (A-II) receptors. In the present work, we have studie d the effects of both hormones on ACTH receptor (ACTH-R) mRNA and bind ing sites. Both HAC and BAC expressed several ACTH-R transcripts. Alth ough in both cell types, ACTH and A-II increased ACTH-R transcripts in a time- and dose-dependent manner, the maximal effects were different . Thus, ACTH at 10(-9)M enhanced 21- and 5-fold the level of ACTH-R mR NA and binding sites in HAC, whereas in BAC both parameters were enhan ced only 3-fold. A-II at 10(-7)M increased 17- and 3.5-fold ACTH-R mRN A and binding sites in HAC, whereas in BAG, it caused only a 2-fold in crease in ACTH-R mRNA and a small decrease in receptor number. In HAC, the stimulatory effects of both hormones on ACTH-R mRNA are mainly tr anscriptional, whereas in BAC they are mainly post-transcriptional, by decreasing the rate of degradation of ACTH-R mRNA. The stimulatory ef fects of ACTH on ACTH-R in both HAC and BAC were associated with an en hanced steroidogenic response to further hormonal stimulation. In cont rast, specific species differences were observed with A-II. Thus, in H AC A-II increased ACTH-R mRNA and binding sites and the ACTH-induced c ortisol production, whereas in BAG, A-II caused a slight decrease of A CTH binding sites and steroidogenic desensitization.