ArticleBiology of sex differences2012
BMPR2 expression is suppressed by signaling through the estrogen receptor.
Article in Biology of sex differences, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
74 citing papers in PubMed, 1 synthesis or guideline pooled it, 118 citations in OpenAlex.
- Gender differences in pulmonary arterial hypertension patients with BMPR2 mutation: a meta-analysis.Respiratory research · 2020Pooled it
- Estriol attenuates visceral adiposity and pulmonary artery smooth muscle cell proliferation via ERα-mediated signalling.European heart journal open · 2026Article
- Sex differences in pulmonary (arterial) hypertension: does it matter?Current opinion in pulmonary medicine · 2025Review
- Addressing Sex as a Biological Variable in Preclinical Models of Lung Disease: An Official American Thoracic Society Research Statement.American journal of respiratory and critical care medicine · 2025Article
- Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025Review
- Hormonal influence: unraveling the impact of sex hormones on vascular smooth muscle cells.Biological research · 2024Review
- Article
- Bioinformatics Analysis of the Genetic and Epigenetic Alterations of Bone Morphogenetic Protein Receptors in Metastatic Breast Cancer.Biochemical genetics · 2024Review
- Effects of Hormone Replacement Therapy on Women's Lung Health and Disease.Pulmonary therapy · 2023Review
- Sex-biased TGFβ signalling in pulmonary arterial hypertension.Cardiovascular research · 2023Review
- Human liver single nuclear RNA sequencing implicates BMPR2, GDF15, arginine, and estrogen in portopulmonary hypertension.Communications biology · 2023Article
- Portopulmonary Hypertension: An Updated Review.Transplantation direct · 2023Review
- SOX17 Deficiency Mediates Pulmonary Hypertension: At the Crossroads of Sex, Metabolism, and Genetics.American journal of respiratory and critical care medicine · 2023Article
- Sex-dependent variation in cartilage adaptation: from degeneration to regeneration.Biology of sex differences · 2023Review
- Expression Patterns and Gonadotropin Regulation of the TGF-β II Receptor (Bmpr2) during Ovarian Development in the Ricefield EelInternational journal of molecular sciences · 2022Article
- Hypoxia-induced pulmonary hypertension upregulates eNOS and TGF-β contributing to sex-linked differences inPulmonary circulation · 2022Article
- Review
- Bioactivities and mechanisms of natural medicines in the management of pulmonary arterial hypertension.Chinese medicine · 2022Review
- Gender dimension in cardio-pulmonary continuum.Frontiers in cardiovascular medicine · 2022Review
- Sex and gender in pulmonary arterial hypertension.European respiratory review : an official journal of the European Respiratory Society · 2021Review
14 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
backgroundStudies 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.
methodsA 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.
resultsBMPR2 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.
conclusionsBMPR2 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.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.