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?

• Published in: Molecular and cellular endocrinology Vol. 490; pp. 28 - 36
• Main Authors: Kamble, Prasad G., Pereira, Maria J., Almby, Kristina, Eriksson, Jan W.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 15.06.2019
• Subjects: adipokines; adipose tissue; Adipose Tissue - metabolism; Adult; Aged; antagonists; dexamethasone; Dexamethasone - pharmacology; Estrogen; Estrogen Receptor alpha - antagonists & inhibitors; Estrogen Receptor alpha - genetics; Estrogen Receptor alpha - metabolism; Estrogen Receptor beta - antagonists & inhibitors; Estrogen Receptor beta - genetics; Estrogen Receptor beta - metabolism; estrogen receptors; estrogens; Estrogens - metabolism; Female; gene expression; Gene Expression Regulation - drug effects; Glucocorticoids; Glucocorticoids - metabolism; Human adipose tissue; Humans; Insulin Resistance; Lipocalin-2 - genetics; Lipocalin-2 - metabolism; Lipocalin2; Male; Middle Aged; postmenopause; Postmenopause - genetics; Premenopause - genetics; women; DPN; Glucocorticoids; Estrogen; MPP; PBS-T; DMEM; PEST; Lipocalin2; PHTPP; FCS; LCN2; GAPDH; Human adipose tissue; BMI
• ISSN: 0303-7207; 1872-8057; 1872-8057
• DOI: 10.1016/j.mce.2019.04.002

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. •Estradiol (E2) increased adipokine lipocalin 2 (LCN2) expression in subcutaneous adipose tissue from postmenopausal women.•E2 seems to acts via estrogen receptor (ER) β to regulate LCN2 expression.•Glucocorticoids selectively interact with ERs to regulate LCN2 expression in adipose tissue.•ERβ and ERα pathways have opposite effects on LCN2 expression and that they interact with glucocorticoid pathways.