Characterization of corticotropin receptors in human adrenocortical cells.

[125I-Tyr23,Phe2,Nle4]ACTH-(1-38) ([125I]ACTH analog), which is equipotent with ACTH, was used to characterize ACTH receptors in human adrenocortical cells. Adrenals were obtained from brain-dead patients at the time of renal harvest with permission. Binding of [125I]ACTH analog to human adrenocortical cells was highly specific, rapid, reversible, and saturable. Analysis of the inhibition of binding of [125I]ACTH analog by ACTH was compatible with a single class of binding sites with an apparent dissociation constant (Kd) of 1.6 nM and a mean binding capacity of 3560 sites/cell. Concentration-response curves for cAMP and cortisol production were shifted to the left of the binding curve, with ACTH concentrations required for half-maximal stimulation being 20- and 720-fold less, respectively, than those for binding. Extracellular calcium was essential for binding and stimulation of cAMP production. These results indicate that human adrenocortical cells contain a single class of ACTH receptors which are highly similar in affinity, capacity, and calcium requirement to those of rat adrenocortical cells, but differ from the rat receptors in the concentration of ACTH needed for cAMP generation.