Glycyrrhetinic acid, an inhibitor of 11 beta-hydroxysteroid dehydrogenase, alters local cerebral glucose utilization in vivo.
11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) metabolizes corticosterone (B) to inactive 11-dehydrocorticosterone and thus protects the non-specific renal mineralocorticoid receptor from exposure to B in vivo. There is regional 11 beta-OHSD mRNA expression and bioactivity in brain in vitro, but any in vivo function is unknown. We used the [14C]2-deoxyglucose technique in conscious rats to investigate whether 11 beta-OHSD inhibition with glycyrrhetinic acid alters local cerebral metabolic activity. We found increased glucose use in subregions of the hypothalamus, hippocampus, neocortex and subthalamus. Thus, 11 beta-OHSD may play a role in regulating the effects of B in the brain, in vivo.
Seckl
J R
JR
Department of Medicine, University of Edinburgh, Western General Hospital, Scotland.
Kelly
P A
PA
Sharkey
J
J
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003847:Deoxyglucose / Q000378:metabolism*; D006034:Glycyrrhetinic Acid / Q000494:pharmacology*; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors* / Q000235:genetics; D007700:Kinetics; D008297:Male; D009928:Organ Specificity; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains
D012333:RNA, Messenger; D003847:Deoxyglucose; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D006034:Glycyrrhetinic Acid