21-Hydroxy-6,19-oxidoprogesterone: a novel synthetic steroid with specific antiglucocorticoid properties in the rat

VICENT GP, MONTESERÍN MC, VELEIRO AS, BURTON G, LANTOS CP, GALIGNIANA MD

MOLECULAR PHARMACOLOGY

AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS

Año: 1997 vol. 52 p. 749 - 753

0026-895X

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.