DISSOCIATION OF CORTICOTROPIN-SUPPRESSING ACTIVITY FROM THE EOSINOPENIC AND HYPERGLYCEMIC ACTIVITIES OF CORTICOSTEROID ANALOGUES*

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Abstract
Although the ACTH-suppressing, eosinopenic, and hyperglycemic activites of corticosteroids were previously considered to be inseparable, 3 synthetic cortisol analogues were found to exhibit significant degrees of dissociation among these biological activities. These 3 compounds were 9[alpha]-fluoro-11[beta], 17[alpha]-dihydroxy- 41,4-pregnene-3,20-dione; 9[alpha],21-difluoro-11[beta],17[alpha]-dihydroxy- 44-pregnene-3,20-dione; and 6[alpha]-methyl-9[alpha]-fluoro-11[beta],-17-dihydroxy-[DELTA] 1,4 pregnene-3,20-dione-21-mesylate. When compared with 9[alpha]-fluoro-11[beta],17[alpha],21-trihydroxy- [DELTA]1,4-pregnene-3,20-dione as a biological standard, all 3 of the above steroids were somewhat less effective as ACTH-suppressing agents but almost totally ineffective as eosinopenic and hyperglycemic agents. The degree of dissociation of ACTH-suppressing activity from eosinopenic and hyperglycemic activities became greater as dosage was increased and was statistically significant at the higher dosage levels for each of the 3 steroids.