Grohé C, Kahlert S, Löbbert K, Vetter H
Medizinische Universitäts-Poliklinik, University of Bonn, Germany.
J Endocrinol. 1998 Feb;156(2):R1-7. doi: 10.1677/joe.0.156r001.
The role of cardiac oestrogen receptor expression and local oestrogen synthesis in the pathogenesis of cardiovascular disease is poorly understood. Therefore we studied the effects of the oestrogen precursors androstendione and testosterone on the expression of cyp450 aromatase, oestrogen receptor alpha and beta, and inducible NO synthase (iNOS) in neonatal rat cardiac myocytes. Here, we show that cyp450 aromatase is expressed in cardiac myocytes and incubation of cardiac myocytes with oestrogen precursors leads to sexual dimorphic transactivation of an oestrogen-responsive reporter plasmid. Furthermore, incubation with oestrogen precursors stimulated expression of oestrogen receptor alpha and beta, and iNOS in a gender-specific fashion. These data suggest that local oestrogen biosynthesis of the heart is effective to activate oestrogen receptor alpha and beta, and downstream target genes in a gender-based fashion and may therefore contribute to the beneficial effects of oestrogen in the pathogenesis of cardiovascular disease.
心脏雌激素受体表达及局部雌激素合成在心血管疾病发病机制中的作用目前尚不清楚。因此,我们研究了雌激素前体雄烯二酮和睾酮对新生大鼠心肌细胞中细胞色素P450芳香化酶、雌激素受体α和β以及诱导型一氧化氮合酶(iNOS)表达的影响。在此,我们表明细胞色素P450芳香化酶在心肌细胞中表达,并且用雌激素前体孵育心肌细胞会导致雌激素反应性报告质粒的性别二态性反式激活。此外,用雌激素前体孵育以性别特异性方式刺激了雌激素受体α和β以及iNOS的表达。这些数据表明,心脏局部雌激素生物合成能以性别为基础有效激活雌激素受体α和β以及下游靶基因,因此可能有助于雌激素在心血管疾病发病机制中的有益作用。