21-Hydroxy-6,19-oxidoprogesterone: a novel synthetic steroid with specific antiglucocorticoid properties in the rat.
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 (approximately 100 microg/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 microM 21OH-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.
Vicent
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GP
Departamentos de Química Biológica, Universidad de Buenos Aires and PRHOM-Consejo Nacional de Investigaciones Científicas y Técnicas, Ciudad Universitaria, (1428) Buenos Aires, Argentina.
Monteserín
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Veleiro
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Burton
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Lantos
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Galigniana
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D000450:Aldosterone / Q000378:metabolism; D000732:Androstanols / Q000378:metabolism; D000818:Animals; D007668:Kidney / Q000378:metabolism; D008297:Male; D011374:Progesterone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D013148:Spironolactone / Q000031:analogs & derivatives / Q000378:metabolism; D013329:Structure-Activity Relationship; D013950:Thymus Gland / Q000378:metabolism; D014156:Transcortin / Q000378:metabolism; D014316:Tritium
C108699:21-hydroxy-6,19-oxidoprogesterone; D000732:Androstanols; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D014316:Tritium; D013148:Spironolactone; D000450:Aldosterone; D011374:Progesterone; C049154:11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one; C054537:ZK 91587; D014156:Transcortin