11 beta-hydroxyprogesterone (HOP) and 11-ketoprogesterone (KP) are reversible components of a shuttle pair whose interconversion in rat liver is catalyzed by isoform-1 of 11 beta-hydroxysteroid dehydrogenase. Kidneys also produce this interconversion. The present study was carried out to investigate the shuttle pair and its components in the rat. As in corticosterone/11-dehydrocorticosterone, oxidation is more effective at an alkaline pH, while reduction prevails at a neutral pH. Moreover, both reactions are inhibited by the detergent 3-[(3-cholamido propyl)-dimethylammonio]-1-propane-sulphonate (CHAPS). However, at variance with the 11-ketosteroids cortisone (E) and 11-dehydrocorticosterone (A) thought to be "inactive," KP has slight direct Na(+)-retaining properties, and it, as well as HOP, induces glucocorticoids (11 beta-hydroxycorticoids) to retain sodium. 11-ketoprogesterone exhibits 17 times better affinity for native type 1 mineralocorticoid receptor than HOP and a 3-fold affinity for partially purified (transcortin free) mineralocorticoid receptor. However, KP, in contrast to HOP, binds only weakly to transcortin, not at all to glucocorticoid receptor, and requires reduction at C11 for tyrosine aminotransferase (TAT) induction.