Affinity of corticosteroids for mineralocorticoid and glucocorticoid receptors of the rabbit kidney: Effect of steroid substitution (original) (raw)

1986, Journal of Steroid Biochemistry

<orticosteroid derivatives coupled in the C,, C, or C,, position with a long aliphatic chain were synthesized in order to select a suitable ligand for the preparation of a biospecific affinity adsorbent for mineralocorticoid receptor purification. The affinity of these derivatives for mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) was explored in rabbit kidney cytosol. In this model, aldosterone bound to a single class of receptors with high affinity (Kd 1 nM) and mineralocorticoid specificity. RU26988, a highly specific ligand for GR, did not compete for these sites. The C, and C,, positions were found to be of crucial importance in the steroid's interaction with the mineralocorticold receptors, since the linkage of a long side chain in these positions induced complete loss of affinity. Hence, deoxycorticosterone no longer bound to MR after 17/3 substitution with a 9-carbon aliphatic chain. This loss of affinity was not observed for glucocorticoids. The 17/3 nonylamide derivative of dexamethasone still competed for GR. Increasing the length of the C, side of the spirolactone SC26304 suppressed its affinity for MR. Finally, C, was an appropriate position for steroid substitution. The 3-nonylamide of carboxymethyloxime deoxycorticosterone bound to MR but not to GR, and therefore constitutes a suitable ligand for the preparation of a mineralocorticoid adsorbent.