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E316 11 hydroxysteroid dehydrogenase type 1 – Single or Return

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					E316    11 hydroxysteroid dehydrogenase type 1 – Single or Return
        fare?
        De Sousa Peixoto, Ricardo A, Morton NM, Chapman KE and
        Seckl JR
        Endocrine Unit, University of Edinburgh, Molecular Medicine
        Centre, Western General Hospital, EH4 2XU, Edinburgh,
        Scotland, UK

Elevated adipose 11 -hydroxysteroid dehydrogenase type1 (11bHSD1) is
implicated in the development of obesity and metabolic syndrome. In
most intact cells, 11 HSD1 regenerates glucocorticoids (GCs) by reducing
inert 11-keto metabolites, amplifying intracellular GC action. However, it
has been proposed that 11 HSD1 acts as a dehydrogenase (inactivating
GCs) in human visceral preadipocytes with a switch to reductase
occurring upon differentiation. We find that primary mouse
preadipocytes similarly express 11 HSD1 mRNA and activity. However, in
contrast to human visceral preadipocytes, 11 HSD1 activity in cultured
mouse preadipocytes is predominantly reductase. Furthermore, the ratio
of 11 -reductase/dehydrogenase activity did not change throughout dif-
ferentiation. In freshly isolated and overnight cultured preadipocytes we
found that reductase activity is higher in mesenteric vs subcutaneous
preadipocytes (2.5 fold difference; p 0.05). We conclude that 11 HSD1
activity in mouse preadipocytes in long-term and short-term culture is
predominantly a keto-reductase and does not change upon differentia-
tion. Furthermore, 11 HSD1 expression increases during differentiation,
consistent with a role in amplifying GC action in mature adipocytes.

				
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posted:2/17/2011
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