Specific nuclear localization of 11-dehydrocorticosterone in rat colon: evidence for a novel corticosteroid receptor.
When colonic crypt cells isolated from intact rats are incubated with [3H]corticosterone specific nuclear binding is displaced by neither aldosterone nor the antiglucocorticoid RU38486, suggesting that [3H]corticosterone is binding to a site distinct from classical mineralocorticoid and glucocorticoid receptors. TLC revealed that the predominant nuclear [3H]steroid in the nucleus of [3H]corticosterone-incubated colonic crypt cells is [3H]11-dehydrocorticosterone. Where the enzyme 11 beta-hydroxysteroid dehydrogenase converting corticosterone to 11-dehydrocorticosterone is absent (cytosol preparations), [3H]corticosterone binds to classical glucocorticoid and mineralocorticoid receptors; in whole cells when 11 beta-hydroxysteroid dehydrogenase is blocked by carbenoxolone, cytoplasmic and nuclear binding of authentic [3H]corticosterone rises. Saturation and Scatchard analyses of nuclear [3H]11-dehydrocorticosterone binding demonstrate a single saturable binding site with a dissociation constant of < or = 10 nM at 22 C. We interpret these studies as evidence for a novel 11-dehydrocorticosterone-preferring receptor that may mediate glucocorticoid effects in tissues with high level of 11 beta-hydroxysteroid dehydrogenase activity.
Sheppard
K E
KE
Baker Medical Research Institute, Prahran, Victoria, Australia.
Funder
J W
JW
D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D002229:Carbenoxolone / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism*; D003106:Colon / Q000166:cytology / Q000378:metabolism*; D003345:Corticosterone / Q000031:analogs & derivatives* / Q000378:metabolism; D008297:Male; D015735:Mifepristone / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D014018:Tissue Distribution
D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D015735:Mifepristone; D000450:Aldosterone; C003552:11-dehydrocorticosterone; D002229:Carbenoxolone; D003345:Corticosterone