TY - JOUR
T1 - Physiological roles of 11β-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase
AU - White, Perrin C.
AU - Rogoff, Daniela
AU - McMillan, D. Randy
PY - 2008/8
Y1 - 2008/8
N2 - Purpose of Review: Inactive cortisone is converted to active cortisol by the reductase activity of 11β-hydroxysteroid dehydrogenase type 1, which can thus increase glucocorticoid effects in target tissues. This paper reviews the functional role(s) of 11β-hydroxysteroid dehydrogenase type 1 and examines factors influencing its activity. Recent Findings: In obese humans, 11β-hydroxysteroid dehydrogenase type 1 is relatively highly expressed in adipose tissue. In mice, overexpression of 11β-hydroxysteroid dehydrogenase type 1 in adipose or liver causes obesity or insulin resistance, respectively, whereas mice lacking 11β-hydroxysteroid dehydrogenase type 1 resist diet-induced obesity and are insulin-sensitive. Thus, 11β-hydroxysteroid dehydrogenase type 1 is a promising drug target for treating the metabolic syndrome and type 2 diabetes. Studies in vitro and in mutant mice demonstrate that the reductase activity of 11β-hydroxysteroid dehydrogenase type 1 depends on reduced nicotinamide adenine dinucleotide phosphate synthesized within the endoplasmic reticulum by hexose-6-phosphate dehydrogenase. Apparent cortisone reductase deficiency is characterized by androgen excess in women or children and decreased urinary excretion of cortisol metabolites. Although polymorphisms in the genes encoding 11β-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase were initially implicated in this condition, subsequent reports have not confirmed this. Summary: Hexose-6-phosphate dehydrogenase and 11β-hydroxysteroid dehydrogenase type 1 may play important roles in the pathogenesis of obesity and metabolic syndrome. Although the importance of polymorphisms in the corresponding genes remains uncertain, rare mutations have not been ruled out.
AB - Purpose of Review: Inactive cortisone is converted to active cortisol by the reductase activity of 11β-hydroxysteroid dehydrogenase type 1, which can thus increase glucocorticoid effects in target tissues. This paper reviews the functional role(s) of 11β-hydroxysteroid dehydrogenase type 1 and examines factors influencing its activity. Recent Findings: In obese humans, 11β-hydroxysteroid dehydrogenase type 1 is relatively highly expressed in adipose tissue. In mice, overexpression of 11β-hydroxysteroid dehydrogenase type 1 in adipose or liver causes obesity or insulin resistance, respectively, whereas mice lacking 11β-hydroxysteroid dehydrogenase type 1 resist diet-induced obesity and are insulin-sensitive. Thus, 11β-hydroxysteroid dehydrogenase type 1 is a promising drug target for treating the metabolic syndrome and type 2 diabetes. Studies in vitro and in mutant mice demonstrate that the reductase activity of 11β-hydroxysteroid dehydrogenase type 1 depends on reduced nicotinamide adenine dinucleotide phosphate synthesized within the endoplasmic reticulum by hexose-6-phosphate dehydrogenase. Apparent cortisone reductase deficiency is characterized by androgen excess in women or children and decreased urinary excretion of cortisol metabolites. Although polymorphisms in the genes encoding 11β-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase were initially implicated in this condition, subsequent reports have not confirmed this. Summary: Hexose-6-phosphate dehydrogenase and 11β-hydroxysteroid dehydrogenase type 1 may play important roles in the pathogenesis of obesity and metabolic syndrome. Although the importance of polymorphisms in the corresponding genes remains uncertain, rare mutations have not been ruled out.
KW - Cortisol
KW - Endoplasmic reticulum
KW - Metabolic syndrome
KW - Pentose phosphate pathway
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U2 - 10.1097/MOP.0b013e328305e439
DO - 10.1097/MOP.0b013e328305e439
M3 - Review article
C2 - 18622204
AN - SCOPUS:52449089631
SN - 1040-8703
VL - 20
SP - 453
EP - 457
JO - Current opinion in pediatrics
JF - Current opinion in pediatrics
IS - 4
ER -