21-Hydroxy-6,19-oxidoprogesterone: A Novel Synthetic Steroid with Specific Antiglucocorticoid Properties in the Rat

  1. G. P. Vicent1,3,
  2. M. C. Monteserín2,
  3. A. S. Veleiro2,
  4. G. Burton2,
  5. C. P. Lantos1,3 and
  6. M. D. Galigniana1,1,3
  1. 1Departamentos de Quı́mica Biológica (G.P.V., C.P.L., M.D.G) and 2Quı́mica Orgánica (M.C.M., A.S.V., G.B.), 3Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires and PRHOM-Consejo Nacional de Investigaciones Cientı́ficas y Técnicas (G.P.V., C.P.L., M.D.G.), Ciudad Universitaria, (1428) Buenos Aires, Argentina

    Abstract

    In the rat, the conformationally highly bent steroid 21-hydroxy-6,19-oxidoprogesterone efficiently displaces [3H]corticosterone from thymus-glucocorticoid receptors and blocks type II receptors in kidney cytosols but competes with neither [3H]aldosterone for kidney-mineralocorticoid receptors nor [3H]progesterone for uterus-progesterone receptors. It evokes Na+ retention only at very high doses (∼100 μg/100 g of rat weight) and is unable to induce tyrosine aminotransferase or to increase glycogen deposits in rat liver. When coincubated with corticosterone or dexamethasone, 2.5 μm21OH-6OP inhibits 80% of tyrosine aminotransferase induction. It may therefore be used experimentally as an antiglucocorticoid virtually lacking mineralocorticoid or glucocorticoid properties as well as affinity for mineralocorticoid or progesterone receptors.

    Footnotes

    • Send reprint requests to: Dr. G. P. Vicent, Departamento de Quı́mica Biológica, Ciudad Universitaria, Pabellón 2.–1428 Buenos Aires, Argentina. E-mail:gvicent{at}qb.fcen.uba.ar

    • ↵1 Current affiliation: Department of Pharmacology, The University of Michigan Medical School, Ann Arbor, MI 48109-0632

    • Abbreviations:
      GR
      glucocorticoid receptor
      GC
      glucocorticoid
      MC
      mineralocorticoid
      MR
      mineralocorticoid receptor
      PR
      progesterone receptor
      P4
      progesterone
      21OH-6OP
      21-hydroxy-6,19-oxidoprogesterone
      6OP
      6,19-oxidoprogesterone
      ALDO
      aldosterone
      DXM
      dexamethasone
      TEGM
      Tris/EDTA/glycerol/mercaptoethanol
      CBG
      transcortin
      RBA
      relative binding affinity
      TAT
      tyrosine aminotransferase
      • Received February 18, 1997.
      • Accepted April 24, 1997.
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    1. Molecular Pharmacology October 1, 1997 vol. 52 no. 4 749-753
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