Physiological roles of 11 beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase.

Abstract

PURPOSE OF REVIEW:

Inactive cortisone is converted to active cortisol by the reductase activity of 11 beta-hydroxysteroid dehydrogenase type 1, which can thus increase glucocorticoid effects in target tissues. This paper reviews the functional role(s) of 11 beta-hydroxysteroid dehydrogenase type 1 and examines factors influencing its activity.

RECENT FINDINGS:

In obese humans, 11 beta-hydroxysteroid dehydrogenase type 1 is relatively highly expressed in adipose tissue. In mice, overexpression of 11 beta-hydroxysteroid dehydrogenase type 1 in adipose or liver causes obesity or insulin resistance, respectively, whereas mice lacking 11 beta-hydroxysteroid dehydrogenase type 1 resist diet-induced obesity and are insulin-sensitive. Thus, 11 beta-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 11 beta-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 11 beta-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 11 beta-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.

• Authors: Perrin C White, Daniela Rogoff, D Randy McMillan
• Journal: Current opinion in pediatrics (Curr Opin Pediatr) Vol. 20 Issue 4 Pg. 453-7 (Aug 2008) ISSN: 1531-698X [Electronic] United States
• PMID: 18622204 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)

Chemical References

• Glucocorticoids
• Carbohydrate Dehydrogenases
• galactose-6-phosphate dehydrogenase
• 11-beta-Hydroxysteroid Dehydrogenase Type 1
• Cortisone Reductase

Topics

• 11-beta-Hydroxysteroid Dehydrogenase Type 1 (genetics, physiology)
• Animals
• Carbohydrate Dehydrogenases (genetics, physiology)
• Cortisone Reductase (deficiency, genetics)
• Endoplasmic Reticulum (metabolism)
• Glucocorticoids (metabolism)
• Humans
• Obesity (physiopathology)
• Polymorphism, Genetic