Tissue-Specific Increases in 11β-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 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) which converts inert cortisone to active cortisol is a putative key mediator of metabolic complications in obesity. Increased 11βHSD1 in adipose tissue may contribute to postmenopausal central obesity. We hypothesized that tissue-specific 11βHSD1 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 11βHSD1 activity was estimated by the serum cortisol response after an oral dose of cortisone. Urinary (5α-tetrahydrocortisol+5β-tetrahydrocortisol)/tetrahydrocortisone ratios were higher in postmenopausal women versus premenopausal women in luteal phase (P<0.05), indicating an increased whole-body 11βHSD1 activity. Postmenopausal women had higher 11βHSD1 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 11βHSD1 activity. In conclusion, our results indicate that postmenopausal normal weight women have increased 11βHSD1 activity in adipose tissue and liver. This may contribute to metabolic dysfunctions with menopause and ageing in women.

Gender-dependent association of HSD11B1 single nucleotide polymorphisms with glucose and HDL-C levels

“…The activity of LPL (lipoprotein lipase), which controls fat uptake in adipocytes, is also influenced by estradiol since this hormone has transcriptional inhibitory effects (Homma et al , 2000) and decreases the transcription and enzymatic activity of 11β-HSD1 in rodents (New et al , 2000). Postmenopausal women with normal weight show enhanced 11β-HSD1 activity in adipose tissue and liver (Andersson et al , 2009), suggesting that low estrogen levels may up-regulate 11β–HSD1 activity and contribute to the imbalance of energy metabolism influenced by cortisol. In a study of inflammatory bowel disease, 11β-HSD1 expression was higher in male than in female patients, whereas 11β-HSD2 showed not gender-specific regulation in its expression (Stegk et al , 2009).…”

Tissue-specific dysregulation of cortisol regeneration by 11βHSD1 in obesity: has it promised too much?

“…On the other hand, a low dose of diarylpropiolnitrile (a selective oestrogen receptor β (ERβ) agonist) increases 11βHSD1 expression in Simpson-Golabi-Behmel syndrome (SGBS) adipocytes in vitro, and expression of ERβ is associated with 11βHSD1 expression in subcutaneous adipose tissue in preand post-menopausal women [75]. Increased ERβ-mediated induction of adipose 11βHSD1 may explain why 11βHSD1 activity is increased in post-menopausal women [76], in association with visceral adiposity and metabolic disease.…”

Adipose tissue IL‐8 is increased in normal weight women after menopause and reduced after gastric bypass surgery in obese women

“…A total of 46 healthy premenopausal and postmenopausal women of normal weight were recruited for the first study. Anthropometrics, blood samples and abdominal superficial subcutaneous adipose tissue (SAT) biopsies were collected as described previously 22 . Postmenopausal status was defined as no menstrual periods within the last 12 months.…”