BMPR2 expression is suppressed by signaling through the estrogen receptor

Biology of Sex Differences

Eric D Austin²  Rizwan Hamid²  Anna R Hemnes¹  James E Loyd¹  Tom Blackwell¹  Chang Yu³  John A Phillips III²  Radhika Gaddipati¹  Santhi Gladson¹  Everett Gu²  James West¹  Kirk B Lane¹ 

[1] Department of Medicine, Vanderbilt University Medical Center, 1161 21st Ave S Suite DD-2205, Nashville, TN 37232-2578, USA

[2] Department of Pediatrics, Vanderbilt University Medical Center, 1161 21st Ave S Suite DD-2205, Nashville, TN 37232-2578, USA

[3] Department of Biostatistics, Vanderbilt University Medical Center, 1161 21st Ave S Suite DD-2205, Nashville, TN 37232-2578, USA

关键词: pulmonary hypertension;    expression;    hormones;    estrogen;    BMPR2;   

Others  :  793755
DOI  :  10.1186/2042-6410-3-6

 received in 2011-12-28, accepted in 2012-02-20,  发布年份 2012

【 摘 要 】

Background

Studies in multiple organ systems have shown cross-talk between signaling through the bone morphogenetic protein receptor type 2 (BMPR2) and estrogen pathways. In humans, pulmonary arterial hypertension (PAH) has a female predominance, and is associated with decreased BMPR2 expression. The goal of this study was to determine if estrogens suppress BMPR2 expression.

Methods

A variety of techniques were utilized across several model platforms to evaluate the relationship between estrogens and BMPR2 gene expression. We used quantitative RT-PCR, gel mobility shift, and luciferase activity assays in human samples, live mice, and cell culture.

Results

BMPR2 expression is reduced in lymphocytes from female patients compared with male patients, and in whole lungs from female mice compared with male mice. There is an evolutionarily conserved estrogen receptor binding site in the BMPR2 promoter, which binds estrogen receptor by gel-shift assay. Increased exogenous estrogen decreases BMPR2 expression in cell culture, particularly when induced to proliferate. Transfection of increasing quantities of estrogen receptor alpha correlates strongly with decreasing expression of BMPR2.

Conclusions

BMPR2 gene expression is reduced in females compared to males in live humans and in mice, likely through direct estrogen receptor alpha binding to the BMPR2 promoter. This reduced BMPR2 expression may contribute to the increased prevalence of PAH in females.

【 授权许可】

   
2012 Austin et al; licensee BioMed Central Ltd.

【 图 表 】

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