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

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 ED₅₀ of cortisol biosynthesis in normal and adenomatous tissue. Analogue binding also had corresponding changes in cortisol biosynthesis. The ED₅₀ 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.