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

Kerry J. McInnes*, Therese C. Andersson, Kotryna Simonyte, Ingegerd Soderstrom, Cecilia Mattsson, Jonathan R. Seckl, Tommy Olsson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Objective
11 beta-Hydroxysteroid dehydrogenase type I (11 beta HSD1) regenerates active cortisol from inert cortisone in adipose tissue. Elevated adipose tissue 11 beta HSD1 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 alpha (ER-alpha) and estrogen receptor beta (ER-beta) could influence 11 beta HSD1 in premenopausal and postmenopausal adipose tissues.

Methods
Nineteen premenopausal (aged 26 +/- 5 y; body mass index, 23.6 +/- 1.6 kg/m(2)) and 23 postmenopausal (aged 63 +/- 4 y; body mass index, 23.4 +/- 1.9 kg/m(2)) 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-alpha- and ER-beta-specific agonists for 24 hours. Basic anthropometric data, serum 17 beta-estradiol and progesterone concentrations, ER-alpha and ER-beta messenger RNA (mRNA) levels, and 11 beta HSD1 mRNA, protein, and activity levels were assessed.

Results
ER-beta and 11 beta HSD1, but not ER-alpha, mRNAs were significantly increased in adipose tissue from postmenopausal women compared with premenopausal women. ER-beta had a significant positive correlation with the mRNA level of 11 beta HSD1 in adipose tissue from premenopausal and postmenopausal women. This association between ER-beta and 11 beta HSD1 was greatest in adipose tissue from postmenopausal women. In human Simpson-Golabi-Behmel syndrome adipocytes, diarylpropiolnitrile, a selective ER-beta agonist, increased 11 beta HSD1 mRNA, protein, and activity levels.

Conclusions
We conclude that, in adipose tissue, ER-beta-mediated estrogen signaling can up-regulate 11 beta HSD1 and that this may be of particular importance in postmenopausal women.

Original languageEnglish
Pages (from-to)1347-1352
Number of pages6
JournalMenopause
Volume19
Issue number12
DOIs
Publication statusPublished - Dec 2012

Keywords

  • ADIPOCYTES
  • 11 beta-Hydroxysteroid dehydrogenase type I
  • THERAPY
  • MICE
  • CORTISOL METABOLISM
  • Adipose tissue
  • VISCERAL OBESITY
  • Estrogen receptor beta
  • ALPHA
  • Menopause

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