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Angiotensin II modulates sex steroid receptors and their metabolizing enzymes in rat cardiac fibroblast (701.10)
Author(s) -
Madhavpeddi Lakshmi,
Gonzales Rayna,
Hale Taben
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.701.10
Subject(s) - aromatase , endocrinology , medicine , angiotensin ii , estrogen receptor , testosterone (patch) , receptor , angiotensin converting enzyme , sex steroid , estrogen , cardiac fibrosis , biology , chemistry , fibrosis , steroid , hormone , cancer , breast cancer , blood pressure
Sex steroids influence angiotensin II (AngII)‐induced cardiac remodeling; however, the importance of local sex steroid metabolism in this process is not known. We previously demonstrated that AngII increased aromatase levels, the enzyme that converts testosterone (T) to 17β‐estradiol, in cultured coronary vascular smooth muscle cells. In the present study we investigated the impact of AngII on sex steroid receptor and enzyme expression in primary rat cardiac fibroblasts. Fibroblasts were isolated from adult male rats and treated at P1 in 2% charcoal‐stripped FBS with AngII or vehicle (18h), followed by T (6h) in the presence or absence of anastrozole (aromatase inhibitor; 6.5h). Cardiac fibroblasts expressed receptors ERα, ERβ, and AR, as well as the enzymes aromatase and 5α‐reductase. AngII significantly reduced mRNA expression of ERβ. 5α‐reductase, AR, and ERβ levels increased when anastrazole was administered with T. This is the first demonstration that cardiac fibroblasts express the enzymes and receptors necessary for local sex steroid metabolism and action. Enzymes and receptor levels are differentially impacted by AngII. Additionally, aromatase inhibition in the presence of T alters steroid receptor and 5α‐reductase (testosterone metabolizing enzyme) levels. Given the major role of the fibroblast in pathogenic cardiac remodeling, the relative balance of T to estrogen in these cells may play an important role in the development of AngII‐mediated fibrosis. Grant Funding Source : Supported by American Heart Association