Estrogen and androgen-receptor crosstalk with beta-catenin signaling and sex differences in myocardial hypertrophy

在心血管疾病的表现和结局中存在与性别相关的差异是公认的。然而，这些差异所涉及的分子机制尚不清楚。在这种情况下，性激素及其受体似乎起着重要作用。基于-catenin在早期胚胎心脏发生和心脏重塑中的已知作用，心肌肥大过程中胚胎遗传程序被重新激活的观察，以及-catenin与性激素受体相互作用的发现，我们假设-catenin与雌激素/雄激素受体信号传导之间的串音导致了所观察到的差异。在此背景下，我们将：(1)确定受雌激素或雄激素受体与TCF/-catenin复合物之间的串音调节的基因，(2)研究这些基因是否在心肌肥大的性别差异中发挥作用，(3)表征所涉及的分子机制。

The existence of sex-related differences in the manifestation and outcome of cardiovascular disease is well accepted. However, the molecular mechanisms involved in these differences are unknown. Sex hormones and their receptors appear to play an important role in this context. Based on the known role of -catenin in early embryonic cardiogenesis and in cardiac remodeling, the observation that during myocardial hypertrophy embryonal genetic programs are reactivated, and the finding that -catenin interacts with sex hormone receptors, we hypothesize that a crosstalk between -catenin and estrogen/androgen receptor signaling contributes to the observed differences. In this context, we will: (1) identify genes that are regulated by a crosstalk between estrogen or androgen receptor and the TCF/-catenin complex, (2) investigate whether or not these genes play a role in the sexspecific differences in myocardial hypertrophy, and (3) characterize the molecular mechanisms involved.