Studies of ACTH Antibodies and Their Reactions with Inactive Analogues of ACTH

Abstract

It has been possible to produce neutralizing antibodies to human ACTH, porcine ACTH and synthetic [alpha]124ACTH. These antibodies are gamma globulins. Their in vitro reaction with ACTH does not require complement. Neutralization of ACTH occurs at both 4 and 37 C. The antibody-ACTH complexes are acid dissociable. Antibodies that neutralized human pituitary ACTH also neutralized circulating plasma ACTH from patients with Addison''s disease. Cush-ing''s disease and the "ectopic ACTH syndrome". Utilizing certain antisera that discriminated between human and porcine ACTH, it was shown that human tumor (ectopic) ACTH was immunologically closer to human pituitary ACTH than to porcine pituitary ACTH. The reactions of ACTH antibodies with certain inactive fragments of ACTH ([alpha]11-24ACTH and [alpha]p25-39ACTH) have been construed to suggest that the human and porcine hormones are structurally more similar in their middle portions than in their C-terminal portions. Such reactions also provide evidence that the structural requirements for the immuno-logic reactivity are not identical with those for the biologic activity of ACTH.