ON THE EVIDENCE SUGGESTING A MULTIPLICITY OF ADRENOCORTICOTROPHIC HORMONES: AN EVALUATION OF BIOASSAY METHODS

Abstract

The potency of several protein and non-protein ACTH prepns. was compared with respect to adrenal ascorbic acid depletion, adrenal weight maintenance, adrenal repair, adrenal cholesterol depletion, thymus and lymphatic atrophy, thoracic duct lympho-cyte count reduction, and blood eosinophile depression. The effectiveness of various prepns. was not equal in all tests; e.g. protein prepn. L 1607 M was 1.8 x as potent in depressing adrenal ascorbic acid as in maintaining adrenal weight, whereas acid-digested polypeptide L 2170 C was 50 times as potent. Similar discrepancies occurred among all tests. Although this may indicate that many different ACTH moieties exist, it may reflect variations in the time-response relationship or the presence of contaminants such as growth hormone. The influence of variations in ACTH molecule size on the absorption rate is important. Rapidly absorbed prepns. favor acute tests (such as ascorbic acid depletion) but are poorly adapted to tests requiring prolonged activity (e.g. adrenal weight or repair tests). Adrenal weight test is responsive to growth hormone in a nonspecific manner. The data neither prove nor disprove the presence of multiple ACTH moieties.