THE DEVELOPMENT OF A REFRACTORY STATE TO ADRENOCORTICOTROPHIC HORMONE1

Abstract

Rats receiving repeated injns. of purified hog ACTH gradually became refractory to a test dose of the hormone which depleted consistently the adrenal ascorbic acid concn. of control rats. After seven weeks of ACTH injns., their response to the test dose was negligible. Serum from such rats contained a substance which consistently diminished the adrenal ascorbic acid depletion normally produced in the hypophysectomized rat by ACTH. Activity of the antiserum wais not demonstrable in vitro by the precipitin technique employed. On a body wt. basis, the dosage level of ACTH producing the refractory state in rats is comparable to that which has been used in man in the treatment of rheumatoid arthritis. Some possible implications of this finding are discussed.