Upregulation of adipose 11-Β-hydroxysteroid dehydrogenase type 1 expression in ovariectomized rats is due to obesity rather than lack of estrogen

Abstract

Objective:Increased tissue activity of cortisol induced by the activation of inert cortisone to active cortisol through 11-Β-hydroxysteroid dehydrogenase type 1 (11Β-HSD1) may play a role in the metabolic syndrome. We recently found that 11Β-HSD1 in subcutaneous adipose tissue (AT) was lower in lean women compared with lean men. Estrogen suppresses hepatic and renal 11Β-HSD1 in rats; hence we investigated the in vitro effect of estrogen on human and rat AT, and the in vivo effects on rat AT 11Β-HSD1 expression.Methods and Procedures:Wistar rats were divided into four groups of eight animals. One group was sham-operated (controls) and others were ovariectomized (OVX). One OVX group was left untreated (OVX-E), another (OVXE) received estrogen treatment, and one received a hypo-caloric diet (OVX-ED), matching the weight gain of the control group. AT from women undergoing liposuction or surgery and from killed male and female rats were incubated with estrogen alone or in the presence of IL-1Β. Gene expressions were determined by real-time reverse transcriptase PCR.Results:Ovariectomy resulted in a 280% increase in adipose 11Β-HSD1 expression P < 0.05). 11Β-HSD1 expression in the (OVXE)-group was significantly reduced compared with the nonsubstituted group (P < 0.05). 11Β-HSD1 expression in the (OVX-ED)-group was reduced significantly (P < 0.05) when compared with the level of the estrogen-substituted group. No significant differences between the control group, the (OVXE)-group, and the (OVX-ED)-group were found. In the in vitro studies, no direct effect of estrogen on adipose 11Β-HSD1 was found.Discussion:The upregulation of 11Β-HSD1 in ovariectomized rats was most likely due to changes in body composition rather than lack of estrogen. © 2008 The Obesity Society.