BMPR2 expression is suppressed by signaling through the estrogen receptor
<p>Abstract</p> <p>Background</p> <p>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 predominanc...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2012-02-01
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| Series: | Biology of Sex Differences |
| Subjects: | |
| Online Access: | http://www.bsd-journal.com/content/3/1/6 |
| _version_ | 1818347809329381376 |
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| author | Austin Eric D Hamid Rizwan Hemnes Anna R Loyd James E Blackwell Tom Yu Chang Phillips III John A Gaddipati Radhika Gladson Santhi Gu Everett West James Lane Kirk B |
| author_facet | Austin Eric D Hamid Rizwan Hemnes Anna R Loyd James E Blackwell Tom Yu Chang Phillips III John A Gaddipati Radhika Gladson Santhi Gu Everett West James Lane Kirk B |
| author_sort | Austin Eric D |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p> |
| first_indexed | 2024-12-13T17:40:04Z |
| format | Article |
| id | doaj.art-37978ab229d94ae28d4161f9a357489b |
| institution | Directory Open Access Journal |
| issn | 2042-6410 |
| language | English |
| last_indexed | 2024-12-13T17:40:04Z |
| publishDate | 2012-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Biology of Sex Differences |
| spelling | doaj.art-37978ab229d94ae28d4161f9a357489b2022-12-21T23:36:48ZengBMCBiology of Sex Differences2042-64102012-02-0131610.1186/2042-6410-3-6BMPR2 expression is suppressed by signaling through the estrogen receptorAustin Eric DHamid RizwanHemnes Anna RLoyd James EBlackwell TomYu ChangPhillips III John AGaddipati RadhikaGladson SanthiGu EverettWest JamesLane Kirk B<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p>http://www.bsd-journal.com/content/3/1/6BMPR2estrogenhormonesexpressionpulmonary hypertension |
| spellingShingle | Austin Eric D Hamid Rizwan Hemnes Anna R Loyd James E Blackwell Tom Yu Chang Phillips III John A Gaddipati Radhika Gladson Santhi Gu Everett West James Lane Kirk B BMPR2 expression is suppressed by signaling through the estrogen receptor Biology of Sex Differences BMPR2 estrogen hormones expression pulmonary hypertension |
| title | BMPR2 expression is suppressed by signaling through the estrogen receptor |
| title_full | BMPR2 expression is suppressed by signaling through the estrogen receptor |
| title_fullStr | BMPR2 expression is suppressed by signaling through the estrogen receptor |
| title_full_unstemmed | BMPR2 expression is suppressed by signaling through the estrogen receptor |
| title_short | BMPR2 expression is suppressed by signaling through the estrogen receptor |
| title_sort | bmpr2 expression is suppressed by signaling through the estrogen receptor |
| topic | BMPR2 estrogen hormones expression pulmonary hypertension |
| url | http://www.bsd-journal.com/content/3/1/6 |
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