title: Tissue-specific increases in 11beta-hydroxysteroid dehydrogenase type 1 in normal weight postmenopausal women.
abstract: 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 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) which converts inert cortisone to active cortisol is a putative key mediator of metabolic complications in obesity. Increased 11betaHSD1 in adipose tissue may contribute to postmenopausal central obesity. We hypothesized that tissue-specific 11betaHSD1 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 11betaHSD1 activity was estimated by the serum cortisol response after an oral dose of cortisone. Urinary (5alpha-tetrahydrocortisol+5beta-tetrahydrocortisol)/tetrahydrocortisone ratios were higher in postmenopausal women versus premenopausal women in luteal phase (P<0.05), indicating an increased whole-body 11betaHSD1 activity. Postmenopausal women had higher 11betaHSD1 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 11betaHSD1 activity. In conclusion, our results indicate that postmenopausal normal weight women have increased 11betaHSD1 activity in adipose tissue and liver. This may contribute to metabolic dysfunctions with menopause and ageing in women.
authors.affiliation: Division of Medicine, Department of Public Health and Clinical Medicine, Umeå University Hospital, Umeå, Sweden.
authors.forename: Therése
authors.initials: T
authors.lastname: Andersson
authors.forename: Kotryna
authors.initials: K
authors.lastname: Simonyte
authors.forename: Ruth
authors.initials: R
authors.lastname: Andrew
authors.forename: Magnus
authors.initials: M
authors.lastname: Strand
authors.forename: Jonas
authors.initials: J
authors.lastname: Burén
authors.forename: Brian R
authors.initials: BR
authors.lastname: Walker
authors.forename: Cecilia
authors.initials: C
authors.lastname: Mattsson
authors.forename: Tommy
authors.initials: T
authors.lastname: Olsson
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism*; D000273:Adipose Tissue / Q000201:enzymology; D000305:Adrenal Cortex Hormones / Q000097:blood / Q000652:urine; D000328:Adult; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D001835:Body Weight / Q000502:physiology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008055:Lipids / Q000097:blood; D008099:Liver / Q000201:enzymology; D008875:Middle Aged; D009928:Organ Specificity / Q000502:physiology*; D017698:Postmenopause / Q000097:blood / Q000502:physiology* / Q000652:urine; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D040521:Subcutaneous Tissue / Q000201:enzymology
chemical_list: D000305:Adrenal Cortex Hormones; D008055:Lipids; D012333:RNA, Messenger; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D001141:Aromatase