19-NOR DEOXYCORTKOSTERONE (19-nor DOC): MINERALOCORTICOID RECEPTOR AFFINITY HIGHER THAN ALDOSTERONE, ELECTROLYTE ACTIVITY LOWER.+

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Abstract
By screening urine extracts from rats with adrenal regeneration hypertension, a steroid was found, subsequently identified as 19-nor DOC, with high affinity for tritiated aldosterone (3HA) binding sites in rat kidney cytosol. The affinity of authentic 19-nor DOC for mineralocorticoid receptors, its binding in plasma and its activity were studied in the rat urinary mineralocorticoid assay. When kidney slices from adrenalectomized rats were incubated in protein-free buffer with 3HA, 19-nor DOC consistently competed better ( .apprx. 140%) for 3HA binding sites than did equivalent concentrations of non-radioactive aldosterone. Under identical conditions, save for the inclusion of 20% adrenalectomized rat plasma in the incubation medium, 19-nor DOC showed only .apprx. 40% the potency of aldosterone in displacing 3HA. Determination of renal binding of 3HA after injection of 3HA .+-. aldosterone .+-. 19-nor DOC in vivo similarly showed 19-nor DOC to be .apprx. 1/3 as potent a competitor for 3HA binding sites as aldosterone. In the rat urinary bioassay 19-nor DOC shows no antagonist activity when injected with aldosterone; in the absence of aldosterone 19-nor DOC acts as a mineralocorticoid agonist with an apparent potency 10-30% that of aldosterone. At a molecular level 19-nor DOC has a higher affinity than aldosterone for mineralocorticoid receptors; in vivo its potency in terms of receptor occupancy is markedly lower than that of aldosterone, due to higher levels of plasma binding; in effector terms 19- nor DOC is a full agonist without antagonist activity.