Angiotensin II receptors of human and primate adrenal fasciculata and glomerulosa: Correlations of binding and steroidogenesis

Abstract

Subcellular fraction and collagenase-dispersed isolated adrenal fasciculata and glomerulosa cells from human and primate adrenal glands and cortisol-producing tumors have been utilized to study angiotensin II (Ang II) receptors and steroid biosynthesis. The receptor density of glomerulosa was threefold higher than that of fasciculata. A benign cortisol-producing adenoma did not differ from normal fasciculata, but a malignant tumor had significantly lower affinity binding. Agonist and antagonist analogues of Ang II competed for binding sites commensurate with known biologic activity. The K d of binding to fasciculata (2 nmol/L) correlated well with the ED 50 of cortisol biosynthesis in normal and adenomatous tissue. Analogue binding also had corresponding changes in cortisol biosynthesis. The ED 50 for aldosterone biosynthesis by glomerulosa cells was significantly lower at 55 pmol/L. Fewer receptors in human fasciculata as compared to glomerulosa and a less sensitive response to Ang II are consistent with previous in vitro observations in other species. These studies suggest that there may be a biologically relevant Ang II receptor of human and primate adrenal fasciculata that share many characteristics with the receptor of the glomerulosa.