The role of 11 beta-hydroxysteroid dehydrogenase in central obesity and osteoporosis.
Both central obesity and osteoporosis are common findings in states of glucocorticoid excess. In many tissues, including adipose tissue, hydroxysteroid dehydrogenase type 1 (11beta-HSD1) catalyses the inter-conversion of active glucocorticoid, cortisol (F) and inactive cortisone (E) and regulates exposure to the glucocorticoid receptor. As such, factors which regulate 11beta-HSD1 are likely to have an important role in adipose tissue and bone physiology. Using primary cultures of human adipose stromal cells we have investigated the effect of various factors present within the adipocyte microenvironment for their effects on 11beta-HSD1 expression. IGF-1 caused a dose dependant inhibition of 11beta-HSD1 activity in both subcutaneous and omental stromal cells. Additionally, TNFalpha treatment increased 11beta-HSD1 reductase activity and mRNA expression. In adult human bone, 11beta-HSD1, but not 11beta-HSD2, expression was demonstrated using enzyme activity studies, RT-PCR and immunohistochemistry. In contrast to liver and adipose tissues, where reductase activity predominates, both reductase and dehydrogenase activities of 11beta-HSD1 were evident in bone chips and primary cultures of human osteoblasts. The action of growth factors and cytokines on glucocorticoid sensitive tissues such as adipose tissue and bone may be mediated by modulation of local glucocorticoid metabolism at a pre-receptor level.
Tomlinson
J W
JW
Division of Medical Sciences, University of Birmingham, Queen Elizabeth Hospital, UK.
Bujalska
I
I
Stewart
P M
PM
Cooper
M S
MS
D042842:11-beta-Hydroxysteroid Dehydrogenases; D017667:Adipocytes / Q000201:enzymology; D001842:Bone and Bones / Q000201:enzymology; D002478:Cells, Cultured; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D009249:NADP / Q000494:pharmacology; D009765:Obesity / Q000473:pathology / Q000503:physiopathology*; D009852:Omentum; D010006:Osteoblasts / Q000201:enzymology; D010024:Osteoporosis / Q000473:pathology / Q000503:physiopathology*; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin; D013234:Stem Cells / Q000201:enzymology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007527:Isoenzymes; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009249:NADP; D007334:Insulin-Like Growth Factor I; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases