Estrogen interacts with glucocorticoids in the regulation of lipocalin 2 expression in human adipose tissue. Reciprocal roles of estrogen receptor α and β in insulin resistance?

Affiliation

Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden. Electronic address: [Email]

Abstract

The adipokine lipocalin 2 (LCN2) is linked to insulin resistance. Its expression in human adipose tissue (AT) can be regulated in a sex-specific manner by a synthetic glucocorticoid, dexamethasone, suggesting an underlying role of sex steroids. We show that 17-β-estradiol (E2) dose-dependently increased LCN2 gene expression in subcutaneous AT from postmenopausal women. This was also seen in the presence of estrogen receptor (ER) α antagonist alone but not with ERβ antagonist, suggesting that E2 effects on LCN2 are mediated via ERβ pathway. Dexamethasone alone or E2+dexamethasone had no significant effect on LCN2. However, E2+dexamethasone increased LCN2 expression with ERα-blockade. Dexamethasone reduced ERα but increased ERβ expression. Dexamethasone can regulate LCN2 expression via inhibition of ERα and stimulation of ERβ and may contribute to the development of glucocorticoid-induced insulin resistance in human AT. In conclusion, ERβ and ERα pathways have opposite effects on LCN2 expression and they interact with glucocorticoid action.

Keywords

Estrogen,Glucocorticoids,Human adipose tissue,Lipocalin2,

OUR Recent Articles