Estradiol-mediated improvements in adipose tissue insulin sensitivity are related to the balance of adipose tissue estrogen receptor [alpha] and [beta] in postmenopausal women

We recently demonstrated that short-term estradiol (E.sub.2) treatment improved insulin-mediated suppression of lipolysis in postmenopausal women, but to a greater extent in those who were late compared to early postmenopausal. In this follow-up study we tested whether subcutaneous adipose tissue (SAT) expression of estrogen receptors (ER) [alpha] and [beta] differs between early and late postmenopausal women. We further tested whether the balance of ER[alpha] to ER[beta] in SAT determined the effect of E.sub.2 on SAT insulin sensitivity. The present study included 35 women who were [less than or equal to]6 years past menopause (EPM; n = 16) or [greater than or equal to]10 years past menopause (LPM; n = 19). Fasted SAT samples were taken following 1-week transdermal E.sub.2 treatment or placebo (PL) in a random cross-over design. Samples were analyzed for nuclear/cytosolic protein content and mRNA expression using Western blot and qPCR, respectively. While ESR1 increased slightly (~1.4-fold) following E.sub.2 treatment in both groups, ER[alpha] and ER[beta] protein expression did not differ between groups at baseline or in response to E.sub.2 . However, the balance of ER[alpha]/ER[beta] protein in the SAT nuclear fraction increased 10% in EPM compared to a 25% decrease in LPM women (group x treatment interaction, p