Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2008) 16 OC3.5

‘Sapienza’ University, Rome, Italy.


Introduction: In humans, testosterone treatment affects body fat distribution and metabolism. The mechanisms involved in these processes are not yet fully understood. We investigated whether sex hormones modulate the expression and activity of type1 11-β-hydroxy-steroid-dehydrogenase (11β-HSD1). 11β-HSD1 catalyses the conversion of inactive cortisone into active cortisol, a key step for the development of functional adipocytes. Based on previous studies an inhibition of lipogenic activity of HSD1 would have been predicted.

Methods: Differentiating and mature 3T3-L1 cells were investigated for 11β-HSD1 expression and activity under the various doses of DHT, E2, insulin and liver X receptor (LXR) agonist. Intracellular fat accumulation was also assessed. Gene expression was analyzed by RT-PCR. 11β-HSD1 activity was estimated by interconversion of radiolabelled [3H]-cortisone into [3H]-cortisol after extraction, TLC separation and β-scanning. Lipid accumulation was evaluated using a modified procedure for serum triglycerides and Oil Red O staining.

Results: Form day 4 of differentiation, 3T3-L1 show a steady increase in 11β-HSD1 expression and activity that parallel fat accumulation. Treatment with DHT produced no reduction, but rather a weak increase, of 11β-HSD1 expression (17.3±8.2% DHT 10 nM versus control). Insulin positive effects on 11β-HSD1 activity were not antagonized by androgens. Conversely, E2 showed a slight inhibition of the enzymatic activity with no significant changes in mRNA expression (−9.3±13.9%, E2 1 nM). LXR agonist strongly inhibited 11β-HSD1 expression (−64.3%) and activity (−45.1%) (LXR-A, 1 μM vs C).

Conclusion: In contrast to LXR agonists, androgens do not inhibit the availability of intracellular active glucocorticoids in mature adipocytes. The proposed explanation is that androgens sustain maintenance of a functional phenotype in mature adipocytes through the pro-differentiating effect of 11β-HSD1.

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