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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

19-Nor deoxycorticosterone (19-nor DOC): mineralocorticoid receptor affinity higher than aldosterone, electrolyte activity lower.

By screening urine extracts from rats with adrenal regeneration hypertension, Gomez-Sanchez et al. found a steroid, subsequently identified as 19-nor DOC, with high affinity for tritiated aldosterone (3HA) binding sites in rat kidney cytosol. We here report studies on the affinity of authentic 19-nor DOC for mineralocorticoid receptors, its binding in plasma and its activity 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 (approximately 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 shows only approximately 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 shows 19-nor DOC to be approximately one third 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. Conclusions of the study are therefore (i) at a molecular level, 19-nor DOC has a higher affinity than aldosterone for mineralocorticoid receptors, (ii) in vivo, its potency in terms of receptor occupancy is markedly lower than that of aldosterone, due to higher levels of plasma binding, (iii) in effector terms, 19-nor DOC is a full agonist without antagonist activity.[1]


  1. 19-Nor deoxycorticosterone (19-nor DOC): mineralocorticoid receptor affinity higher than aldosterone, electrolyte activity lower. Funder, J.W., Mercer, J., Ingram, B., Feldman, D., Wynne, K., Adam, W.R. Endocrinology (1978) [Pubmed]
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