DOWN-REGULATION OF ELAVL1 GENE IN THE ADIPOSE TISSUE OF WOMEN WITH PCOS

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 498-523-Female Reproductive Endocrinology & Case Reports
Clinical
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-512
Yen-Hao Chen*1, Saleh Heneidi2 and Ricardo Azziz1
1Georgia Regents University, Augusta, GA, 2Georgia Regents University, Augusta
DOWN-REGULATION OF ELAVL1 GENE IN THE ADIPOSE TISSUE OF WOMEN WITH PCOS

Yen-Hao Chen, Saleh Heneidi, and Ricardo Azziz

Departments of Medicine (R.A.) and Obstetrics/Gynecology (Y.H.C., S.H., R.A.), Medical College of Georgia, Georgia Regents University, Augusta, Georgia

Rationale: The increase in low-grade chronic inflammation in women with PCOS.

Background: PCOS has a familial aggregation and is considered a complex trait; however the genetic basis of this disorder still unclear. In a study of 367 PCOS families a PCOS susceptibility locus, D19S884 on chromosome 19p13.2, has been particularly identified. ELAVL1 maps to within 100 kb of D19S884. ELAVL1/HuR is a RNA binding protein (RBP) which includes two N-terminal RNA recognition motifs (RRM) with high affinity for a U-rich sequence (HuR Binding Motif, HBM) followed by a nucleocytoplasmic shuttling sequence and a C-terminal RRM recognizing the poly (A) tail. The function of ELAVL1 in modulating chronic inflammation is unclear, although studies on microphage cell lines and mouse strains with mutations in the HBM suggest ELAVL1 could stabilize inflammatory mRNAs, therefore fostering or supporting tissue inflammation. Alternatively, studies in myeloid lineage tissue specifically overexpressing HuR suggested that HuR is a negative post-transcriptional modulator of inflammation. In endothelial cells LPL-mediated lipolysis up-regulated the activation of ELAVL1. Furthermore, ELAVL1 has been considered a stabilizer contributing to increased CYP17 gene expression in PCOS theca cells. As ELAVL1 is associated with increased chronic inflammation and increased CYP17 expression fostering androgen production in ovarian theca cells,  we hypothesized that ELAVL1 would be abnormally expressed in the adipose tissue of women with PCOS.

Objectives: To determine if ELAVL1 is abnormally expressed in the adipose tissue of women with PCOS.

Results:  Gene expression of ELAVL1 in subcutaneous adipose tissues was compared between 12 PCOS patients and 15 matched controls. The expression of ELAVL1 was significant decreased in PCOS patients (P=0.0001).

Conclusions: Our results support the hypothesis that ELAVL1 may play a role in the pathophysiology of PCOS, although further study is required to understand whether ELAVL1 is a negative or positive posttranscriptional modulator of inflammation in adipose tissue.

Nothing to Disclose: YHC, SH, RA

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: NIH Grant RO1-DK073632 awarded to RA