19-nor analogs of adrenal steroids: mineralocorticoid and glucocorticoid receptor activity.
The effect of absence of the C-19 methyl group from five adrenal steroids has been studied in terms of their affinity for mineralocorticoid (MR) and glucocorticoid receptors (GR). In MR assays, 19-nordeoxycorticosterone and 19-norprogesterone showed 3-fold higher affinity for MR than did their respective parent steroids; 19-norcortisol had 1.5 times the affinity of cortisol for MR. In contrast, corticosterone and 19-nororticosterone showed equal affinity, and 19-noraldosterone showed less than 1% the MR activity of aldosterone. In GR assays, the absence of the C-19 methyl group from progesterone increased GR affinity 3-fold and deoxycorticosterone affinity 1.5-fold. In contrast, the other 19-nor steroids showed decreased affinity vis à vis their parent compounds (19-norcorticosterone, 30%; 19-norcortisol, 10%; 19-noraldosterone, < 1%). These findings suggest that while the 19-nor analogs of 11-deoxy steroids are consistently more active than their parent steroid, the 19-nor 11-oxygenated adrenal steroids show no predictable pattern of binding for MR or GR.
D000450:Aldosterone / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D003345:Corticosterone / Q000031:analogs & derivatives / Q000378:metabolism; D003900:Desoxycorticosterone / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000378:metabolism; D009653:Norprogesterones / Q000378:metabolism; D009654:Norsteroids / Q000378:metabolism*; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid / Q000378:metabolism*; D013329:Structure-Activity Relationship
D009653:Norprogesterones; D009654:Norsteroids; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid; D003900:Desoxycorticosterone; C019026:19-nordeoxycorticosterone; C027516:19-norcorticosterone; D000450:Aldosterone; C027515:19-norcortisol; C027514:19-noraldosterone; D003345:Corticosterone; D006854:Hydrocortisone