Tissue-Specific Increases in 11 beta-Hydroxysteroid Dehydrogenase Type 1 in Normal Weight Postmenopausal Women

Therese Andersson, Kotryna Simonyte, Ruth Andrew, Magnus Strand, Jonas Buren, Brian R. Walker, Cecilia Mattsson, Tommy Olsson

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With age and menopause there is a shift in adipose distribution from gluteo-femoral to abdominal depots in women. Associated with this redistribution of fat are increased risks of type 2 diabetes and cardiovascular disease. Glucocorticoids influence body composition, and 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta HSD1) which converts inert cortisone to active cortisol is a putative key mediator of metabolic complications in obesity. Increased 11 beta HSD1 in adipose tissue may contribute to postmenopausal central obesity. We hypothesized that tissue-specific 11 beta HSD1 gene expression and activity are up-regulated in the older, postmenopausal women compared to young, premenopausal women. Twenty-three pre- and 23 postmenopausal, healthy, normal weight women were recruited. The participants underwent a urine collection, a subcutaneous adipose tissue biopsy and the hepatic 11 beta HSD1 activity was estimated by the serum cortisol response after an oral dose of cortisone. Urinary (5 alpha-tetrahydrocortisol+5 beta-tetrahydrocortisol)/tetrahydrocortisone ratios were higher in postmenopausal women versus premenopausal women in luteal phase (P<0.05), indicating an increased whole-body 11 beta HSD1 activity. Postmenopausal women had higher 11 beta HSD1 gene expression in subcutaneous fat (P<0.05). Hepatic first pass conversion of oral cortisone to cortisol was also increased in postmenopausal women versus premenopausal women in follicular phase of the menstrual cycle (P<0.01, at 30 min post cortisone ingestion), suggesting higher hepatic 11 beta HSD1 activity. In conclusion, our results indicate that postmenopausal normal weight women have increased 11 beta HSD1 activity in adipose tissue and liver. This may contribute to metabolic dysfunctions with menopause and ageing in women.

Original languageEnglish
Article numbere8475
Pages (from-to)-
Number of pages8
JournalPLoS ONE
Issue number12
Publication statusPublished - 29 Dec 2009

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