Rat liver 11 beta-hydroxysteroid dehydrogenase complementary deoxyribonucleic acid encodes oxoreductase activity in a mineralocorticoid-responsive toad bladder cell line.
The mineralocorticoid receptor displays equal affinity for aldosterone and corticosterone. It has been proposed that aldosterone selectivity in vivo is achieved by the conversion of corticosterone into its inactive metabolite 11-dehydrocorticosterone by 11 beta-hydroxysteroid dehydrogenase (11 beta HSD). To test this hypothesis, we transfected rat liver 11 beta HSD cDNA into TBM cells, a sodium-transporting cell line. These cells respond equally well to aldosterone and corticosterone, indicating that endogenous 11 beta HSD is expressed at low levels in TBM cells. Although exogenous rat liver 11 beta HSD was expressed at high levels in transfected cells, mineralocorticoid selectivity was not observed. By contrast, the biologically inactive 11-dehydrocorticosterone was readily converted into corticosterone, a potent agonist for sodium transport. Our results indicate that rat liver 11 beta HSD behaves predominantly as a reductase in TBM cells. Another 11 beta HSD isoform is likely to be responsible for the dehydrogenase reaction in aldosterone-responsive cells.
Duperrex
H
H
Institut de Pharmacologie et de Toxicologie de l'Université, Lausanne, Switzerland.
Kenouch
S
S
Gaeggeler
H P
HP
Seckl
J R
JR
Edwards
C R
CR
Farman
N
N
Rossier
B C
BC
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000818:Animals; D002460:Cell Line; D003345:Corticosterone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D004848:Epithelium / Q000201:enzymology / Q000502:physiology; D005260:Female; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics* / Q000378:metabolism*; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D010957:Plasmids; D051381:Rats; D013997:Time Factors; D014162:Transfection; D001743:Urinary Bladder / Q000187:drug effects* / Q000201:enzymology*
D003907:Dexamethasone; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; C003552:11-dehydrocorticosterone; D003345:Corticosterone