Δ1-11-oxa-11-deoxycortisol: A new antiglucocorticoid with activity in vivo

G. P. Chrousos, M. A. Sauer, D. L. Loriaux, G. B. Cutler

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Abstract

A new steroid-like compound, Δ1-11-oxa-11-deoxycortisol, was tested in a one-week growth suppression, thymus suppression and adrenal weight suppression bioassay for possible glucocorticoid antagonist activity in vivo. We hypothesized that this compound would have antiglucocorticoid activity based on previous studies of 11-deoxycortisol and Δ1,9(11)-11-deoxycortisol, which were optimal glucocorticoid antagonists in vivo in adrenalectomized rats, but which lost antiglucocorticoid activity in intact animals, apparently due to adrenal 11β-hydroxylation. Thus, Δ1-11-oxa-11-deoxycortisol, a compound which cannot undergo llβ-hydroxylation, was synthesized and tested as an antiglucocorticoid. This analog had an affinity for the rat thymus glucocorticoid receptor similar to that of its parent compounds (Ki 0.9-3.1×10-7M). A dose of 1 mg rat antagonized the effect of 15μg of dexamethasone in the growth suppression assay (p<0.05) and in the thymus suppression assay (p<0.06), but did not antagonize dexamethasone-induced adrenal weight suppression. Δ1-11-oxa-11-deoxycortisol did not exhibit glucocorticoid activity in any of the three assays. These data suggest that Δ1-11-oxa-11-deoxycortisol may be a pure competitive antagonist of dexamethasone.

Original languageEnglish (US)
Pages (from-to)425-431
Number of pages7
JournalSteroids
Volume40
Issue number4
DOIs
StatePublished - Oct 1982

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology
  • Pharmacology
  • Clinical Biochemistry
  • Organic Chemistry

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