Lipocalin 2 deficiency alters estradiol production and estrogen receptor signaling in female mice

Guo, Hong, Zhang, Yuanyuan, Brockman, David A., Hahn, Wendy, Bernlohr, David A. and Chen, Xiaoli (2012) Lipocalin 2 deficiency alters estradiol production and estrogen receptor signaling in female mice. Endocrinology, 153 3: 1183-1193. doi:10.1210/en.2011-1642

Author Guo, Hong
Zhang, Yuanyuan
Brockman, David A.
Hahn, Wendy
Bernlohr, David A.
Chen, Xiaoli
Title Lipocalin 2 deficiency alters estradiol production and estrogen receptor signaling in female mice
Journal name Endocrinology   Check publisher's open access policy
ISSN 0013-7227
Publication date 2012-01-01
Sub-type Article (original research)
DOI 10.1210/en.2011-1642
Open Access Status Not Open Access
Volume 153
Issue 3
Start page 1183
End page 1193
Total pages 11
Place of publication Chevy Chase, MD United States
Publisher The Endocrine Society
Language eng
Formatted abstract
We have previously characterized lipocalin 2 (Lcn2) as a new adipokine having a critical role in energy and lipid metabolism in male mice. Previous studies by others have suggested that Lcn2 is a putative target gene of estrogens. In this study, we reported the effect of Lcn2 deficiency on estradiol biosynthesisandestrogen receptor signaling in female Lcn2-deficient (Lcn2-/-) mice. We found that Lcn2 expression in white adipose tissue is gender, depot, and age dependent. In female mice, Lcn2 is predominantly expressed in inguinal adipose tissue but at relatively very low levels in perigonadal depot and ovary. After 22 wk of high-fat diet (HFD) feeding or at old age, Lcn2-/-female mice had significantly reduced levels of serum 17β-estradiol and down-regulated expression of estrogen receptor α in multiple metabolic tissues. Consistently, the expression of estrogen regulated genes involved in cholesterol homeostasis, such as liver X receptor β and low-density lipoprotein receptor was also down-regulated in the adipose tissue of Lcn2-/- mice. These changes were in line with the development of atherogenic dyslipidemia in response to HFD feeding; female Lcn2-/- mice had significantly elevated levels of total cholesterol and low-density lipoprotein cholesterol, whereas reduced high-density lipoprotein cholesterol levels compared with wild-type female mice. Interestingly,whencomparedwith wild-type controls, HFD-fed female Lcn2-/- mice had significantly reduced expression levels of aromatase, a key enzyme regulating estradiol biosynthesis, in adipose tissue. Moreover, Lcn2 deficiency markedly blunted age-related increase in adipose aromatase expression but had no significant impact on age-related reduction in ovarian aromatase expression. Our findings suggest that Lcn2 has a tissue-specific role in adipose estradiol biosynthesis, which may link Lcn2 to obesity- and age-related estradiol production and metabolic complications in females.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Centre for Integrated Preclinical Drug Development Publications
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