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Abstract

Inhibition of 11ß-hydroxysteroid dehydrogenase enzymatic activities by glycyrrhetinic acid in vivo supports direct glucocorticoid-mediated suppression of steroidogenesis in Leydig cells (PDF) (HTML) 
Hu,Guo-Xin; Lin,Han; Sottas,Chantal M.; Morris,David J.; Hardy,Matthew P.; Ge,Renshan
Journal of Andrology 29(3): 345-351
Publication date: 2008

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Previous studies have suggested that glucocorticoid (GC) candirectly affect testicular testosterone (T) biosynthesis byLeydig cells through a receptor-mediated mechanism. Interconversionof corticosterone (CORT), the active form in rodents, and 11-dehydroCORT,the biologically inert 11-keto form, is catalyzed by 11ßHSD1.This enzyme thus controls the intracellular concentration ofactive GC. We have postulated that elevated CORT levels resultingfrom stress exceed the Leydig cell's capacity for metabolicinactivation of CORT, resulting in suppressed T production.The present study tested whether inhibition of 11ßHSD1in vivo, by the administration of glycyrrhetinic acid (GA),increases intracellular active GC concentration and therebyaffects serum T concentration and Leydig cell T production.Adult Sprague-Dawley rats were treated with vehicle (corn oil),CORT, GA, or GA + CORT. Serum luteinizing hormone (LH), CORT,and T levels were measured, as were the steroidogenic capacitiesof purified Leydig cells. Twofold elevations of CORT were achievedby the administration of either CORT or GA alone, but in bothcases there was no effect on serum T levels. However, whenCORT and GA were administered in combination, serum CORT levelsincreased 3.5-fold (to 420 ± 34 ng/mL) and serum T levelswere reduced significantly (to 0.72 ± 0.07 ng/mL; control,2.12 ± 0.23 ng/mL). Serum levels of LH were not affectedby CORT, GA, or GA + CORT. Consistent with the reduced serumT levels following GA + CORT, steroidogenic enzyme expressionand capacities were significantly reduced compared to control.These data support a role for 11ßHSD1 in modulating intracellularCORT concentrations and, in turn, for a direct effect of GCon Leydig cells in response to stress.

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