%0 Journal Article
%T BMPR2 expression is suppressed by signaling through the estrogen receptor
%A Eric D Austin
%A Rizwan Hamid
%A Anna R Hemnes
%A James E Loyd
%A Tom Blackwell
%A Chang Yu
%A John A Phillips III
%A Radhika Gaddipati
%A Santhi Gladson
%A Everett Gu
%A James West
%A Kirk B Lane
%J Biology of Sex Differences
%D 2012
%I BioMed Central
%R 10.1186/2042-6410-3-6
%X 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.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.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.Bone morphogenetic protein receptor type 2 (BMPR2) is essential for development; mice lacking the gene fail to progress to gastrulation [1]. BMP signaling is essential in almost all tubular organogenesis. In lung, kidney and lacrimal gland formation BMP signaling is central to development [2-4]. The BMP pathway also plays a central role in M¨¹llerian duct regression and Sertoli cell maturation regression [5,6].Beyond its developmental role, signaling through BMPR2 is associated with several adult diseases, including arthritis, pulmonary hypertension, atherosclerosis, diabetic nephropathy, renal fibrosis, and osteoporosis [7-10]. The common role for the BMP pathway in all of these seems to be an inappropriate response to damage to the respective organ. Many of these diseases show a marked gender imbalance in prevalence, and cross-talk between estrogen and BMP signaling has been noted in systems throughout the body [11-13].For inst
%K BMPR2
%K estrogen
%K hormones
%K expression
%K pulmonary hypertension
%U http://www.bsd-journal.com/content/3/1/6