Isozymes of 11 beta-hydroxysteroid dehydrogenase: which enzyme endows mineralocorticoid specificity?
Intracellular enzymes which interconvert circulating hormones between active and inactive forms aid in regulating the biological activity of the ligand in a cell-specific manner. This is particularly important in mineralocorticoid target tissues where glucocorticoids and mineralocorticoids have equivalent affinity for the mineralocorticoid receptor. Inactivation of glucocorticoids at the 11-hydroxyl position by the action of 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) permits the occupation of the mineralocorticoid receptor by aldosterone in the presence of much higher levels of circulating cortisol. The suppression of dehydrogenase activity allows glucocorticoids to activate the mineralocorticoid receptor, leading to classical mineralocorticoid type effects such as sodium retention and potassium excretion. A number of 11 beta-OHSDs are currently candidate protectors of the mineralocorticoid receptor. This review examines the attributes of these 11 beta-hydroxysteroid dehydrogenase isozymes and suggests reasons why a high affinity, NAD-dependent enzyme appears to be the most likely candidate to endow specificity on the mineralocorticoid receptor.
Krozowski
Z S
ZS
Molecular Hypertension Laboratory, Baker Institute of Medical Research, Melbourne, Australia.
Provencher
P H
PH
Smith
R E
RE
Obeyesekere
V R
VR
Mercer
W R
WR
Albiston
A L
AL
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000818:Animals; D006706:Homeostasis; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism*; D008901:Mineralocorticoids / Q000378:metabolism*; D009243:NAD / Q000494:pharmacology; D018161:Receptors, Mineralocorticoid / Q000378:metabolism
D007527:Isoenzymes; D008901:Mineralocorticoids; D018161:Receptors, Mineralocorticoid; D009243:NAD; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases