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Association of 11β-hydroxysteroid dehydrogenase type I expression and activity with estrogen receptor β in adipose tissue from postmenopausal women

McInnes, Kerry J. PhD1; Andersson, Therése C. PhD2; Šimonytė, Kotryna MD, PhD2; Söderström, Ingegerd MD, PhD2; Mattsson, Cecilia MD, PhD2; Seckl, Jonathan R. MD, PhD1; Olsson, Tommy MD, PhD2

doi: 10.1097/gme.0b013e318258aad7
Original Articles

Objective 11β-Hydroxysteroid dehydrogenase type I (11βHSD1) regenerates active cortisol from inert cortisone in adipose tissue. Elevated adipose tissue 11βHSD1 activity is observed in obese humans and rodents, where it is linked to obesity and its metabolic consequences. Menopause is also associated with increased abdominal fat accumulation, suggesting that estrogen is also important in adipose tissue metabolism. The purpose of this current study was to establish whether estrogen signaling through estrogen receptor α (ER-α) and estrogen receptor β (ER-β) could influence 11βHSD1 in premenopausal and postmenopausal adipose tissues.

Methods Nineteen premenopausal (aged 26 ± 5 y; body mass index, 23.6 ± 1.6 kg/m2) and 23 postmenopausal (aged 63 ± 4 y; body mass index, 23.4 ± 1.9 kg/m2) healthy women were studied. Subcutaneous adipose tissue biopsies and fasting venous blood samples were taken. Body composition was measured by bioelectrical impedance analysis. Human Simpson-Golabi-Behmel syndrome adipocyte cells were treated with ER-α– and ER-β–specific agonists for 24 hours. Basic anthropometric data, serum 17β-estradiol and progesterone concentrations, ER-α and ER-β messenger RNA (mRNA) levels, and 11βHSD1 mRNA, protein, and activity levels were assessed.

Results ER-β and 11βHSD1, but not ER-α, mRNAs were significantly increased in adipose tissue from postmenopausal women compared with premenopausal women. ER-β had a significant positive correlation with the mRNA level of 11βHSD1 in adipose tissue from premenopausal and postmenopausal women. This association between ER-β and 11βHSD1 was greatest in adipose tissue from postmenopausal women. In human Simpson-Golabi-Behmel syndrome adipocytes, diarylpropiolnitrile, a selective ER-β agonist, increased 11βHSD1 mRNA, protein, and activity levels.

Conclusions We conclude that, in adipose tissue, ER-β–mediated estrogen signaling can up-regulate 11βHSD1 and that this may be of particular importance in postmenopausal women.

From the 1Endocrinology Unit, Center for Cardiovascular Science, The Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK; and 2Department of Public Health and Clinical Medicine, Medicine, Umeå University, Umeå, Sweden.

Received February 3, 2012; revised and accepted April 3, 2012.

Funding/support: This work was supported by grants from Diabetes UK.

Financial disclosure/conflicts of interest: Jonathan R. Seckl has a financial relationship for consultancy with Boehringer-Ingelheim, Sanofi Aventis, and Astellas.

K.J. McInnes and T.C. Andersson contributed equally to this work.

Address correspondence to: Kerry J. McInnes, PhD, Endocrinology Unit, British Heart Foundation/University Center for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK. E-mail:

©2012The North American Menopause Society