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.