The role of 11 beta-hydroxysteroid dehydrogenase in central obesity and osteoporosis

Both central obesity and osteoporosis are common findings in states of gluc ocorticoid excess. In many tissues, including adipose tissue, 11 beta -hydr oxysteroid dehydrogenase type I (11 beta -HSD1) catalyses the inter-convers ion of active glucocorticoid, cortisol (F) and inactive cortisone (E) and r egulates exposure to the glucocorticoid receptor. As such, factors which re gulate 11 beta -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 adip ocyte microenvironment for their effects on 11 beta -HSD1 expression. IGF-1 caused a dose dependant inhibition of 11 beta -HSD1 activity in both subcu taneous and omental stromal cells. Additionally, TNF alpha treatment increa sed 11 beta -HSD1 reductase activity and mRNA expression. In adult human bo ne, 11 beta -HSD1, but not 11 beta -HSD2, expression was demonstrated using enzyme activity studies, RT-PCR and immunohistochemistry. In contrast to l iver and adipose tissues, where reductase activity predominates, both reduc tase and dehydrogenase activities of 11 beta -HSD1 were evident in bone chi ps and primary cultures of human osteoblasts. The action of growth factors and cytokines on glucocorticoid sensitive tissues such as adipose tissue an d bone may be mediated by modulation of local glucocorticoid metabolism at a pre-receptor level.