Estrogen reduces 11beta-hydroxysteroid dehydrogenase type 1 in liver and visceral, but not subcutaneous, adipose tissue in rats.
Following menopause, body fat is redistributed from peripheral to central depots. This may be linked to the age related decrease in estrogen levels. We hypothesized that estrogen supplementation could counteract this fat redistribution through tissue-specific modulation of glucocorticoid exposure. We measured fat depot masses and the expression and activity of the glucocorticoid-activating enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) in fat and liver of ovariectomized female rats treated with or without 17beta-estradiol. 11betaHSD1 converts inert cortisone, or 11-dehydrocorticosterone in rats into active cortisol and corticosterone. Estradiol-treated rats gained less weight and had significantly lower visceral adipose tissue weight than nontreated rats (P < 0.01); subcutaneous adipose weight was unaltered. In addition, 11betaHSD1 activity/expression was downregulated in liver and visceral, but not subcutaneous, fat of estradiol-treated rats (P < 0.001 for both). This downregulation altered the balance of 11betaHSD1 expression and activity between adipose tissue depots, with higher levels in subcutaneous than visceral adipose tissue of estradiol-treated animals (P < 0.05 for both), opposite the pattern in ovariectomized rats not treated with estradiol (P < 0.001 for mRNA expression). Thus, estrogen modulates fat distribution, at least in part, through effects on tissue-specific glucocorticoid metabolism, suggesting that estrogen replacement therapy could influence obesity related morbidity in postmenopausal women.
Andersson
Therése
T
Department of Public Health and Clinical Medicine, Medicine, Umeå University Hospital, Umeå, Sweden.
Söderström
Ingegerd
I
Simonyté
Kotryna
K
Olsson
Tommy
T
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism*; D000273:Adipose Tissue / Q000201:enzymology; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D050218:Body Fat Distribution; D015536:Down-Regulation; D004958:Estradiol / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D010052:Ovariectomy; D017698:Postmenopause / Q000502:physiology*; D011282:Pregnenediones / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050151:Subcutaneous Fat / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects
D004967:Estrogens; D011282:Pregnenediones; D004958:Estradiol; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1