Effects of gonadectomy on glucocorticoid metabolism in obese Zucker rats
Endocrinology. 2007-10-01; 148(10): 4836-4843
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1. Endocrinology. 2007 Oct;148(10):4836-43. Epub 2007 Jul 12.
Effects of gonadectomy on glucocorticoid metabolism in obese Zucker rats.
Barat P(1), Livingstone DE, Elferink CM, McDonnell CR, Walker BR, Andrew R.
(1)Paediatric Endocrinology, Centre for Cardiovascular Science, University of
Edinburgh, 47 Little France Crescent, Edinburgh, United Kingdom.
Glucocorticoids are metabolized by 11beta-hydroxysteroid dehydrogenase 1
(11betaHSD1) and the A-ring reductases (5alpha- and 5beta-reductases).
Dysregulation of these enzymes has been reported in liver and adipose tissue in
obese humans and animals, potentially leading to altered intracellular
glucocorticoid concentrations and compensatory activation of the
hypothalamic-pituitary-adrenal axis. This dysregulation of glucocorticoid
metabolism in obesity is poorly understood. We hypothesized that changes in
glucocorticoid metabolism in obesity are mediated by alterations in androgen
action. Steroid metabolism was studied in obese and lean male Zucker rats (age 10
wk, 10 animals per group) 4 wk after gonadectomy or sham surgery. Oral glucose
tolerance tests were performed, and activities and abundances of mRNAs for
steroid metabolizing enzymes were quantified in liver and adipose tissue.
Gonadectomy did not consistently alter weight gain, glucose intolerance, or
hyperinsulinemia in obese animals. Gonadectomy increased adrenal mass (P < 0.05), suppressed 11betaHSD1 activity and/or mRNA in liver and adipose, increased 5alpha-reductase 1 mRNA in liver (P < 0.05), and increased 5beta-reductase activity only in obese animals (P < 0.05). Differences in hepatic 11betaHSD1 mRNA expression and adipose activity between lean and obese animals were normalized by gonadectomy, whereas obese gonadectomized animals maintained elevated liver 5alpha-reductase and had an exaggerated elevation of 5beta-reductase activity. We conclude that androgens tonically increase 11betaHSD1 in liver and adipose tissue in male rats and contribute to the dysregulation of 11betaHSD1 in obesity. By contrast, androgens tonically suppress hepatic A-ring reductases in male rats and do not contribute to dysregulation of these enzymes in obesity. DOI: 10.1210/en.2007-0597 PMID: 17628001 [Indexed for MEDLINE]