Increased A-ring reduction of glucocorticoids in obese Zucker rats: effects of insulin sensitization.
OBJECTIVE
Obesity is associated with altered glucocorticoid metabolism, which may impact on hypothalamic-pituitary-adrenal axis activity. Here we characterize hepatic 5alpha- and 5beta-reductase in obese rats and their responses to insulin sensitization.


METHODS
Hepatic A-ring reductase protein and mRNA were assessed in lean and obese Zucker rats after insulin sensitization with metformin or rosiglitazone (n = 7 to 8/group).


RESULTS
Hepatic 5alpha-reductase 1 and 5beta-reductase mRNA and protein (p < 0.01) were increased in obese rats. Insulin sensitization ameliorated increased 5alpha-reductase 1 mRNA in obese rats (p < 0.01) and partially reversed increased 5beta-reductase activity.


CONCLUSIONS
Hepatic clearance of glucocorticoids by 5alpha- and 5beta-reductase is increased in obese Zucker rats, and this increase in clearance is attenuated by insulin sensitization. This increased hepatic clearance may underpin compensatory activation of the hypothalamic-pituitary-adrenal axis in obesity.
Livingstone
Dawn E W
DE
Endocrinology Unit, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK.
McInnes
Kerry J
KJ
Walker
Brian R
BR
Andrew
Ruth
R
D000818:Animals; D042944:Cholestenone 5 alpha-Reductase / Q000096:biosynthesis*; D005938:Glucocorticoids / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D008687:Metformin / Q000494:pharmacology; D009765:Obesity / Q000378:metabolism*; D010088:Oxidoreductases / Q000096:biosynthesis*; D051381:Rats; D011924:Rats, Zucker; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology
D005938:Glucocorticoids; D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D008687:Metformin; D010088:Oxidoreductases; D042944:Cholestenone 5 alpha-Reductase; C051860:cholestenone 5 beta-reductase