Key result
17 beta-oestradiol treatment significantly increased progesterone receptor mRNA by 1.36-fold (P=0.001) and protein levels by 1.40-fold (P=0.03) in female human cardiac tissues, but had no effect in male tissues.
17β-oestradiol upregulates progesterone receptor expression in female but not male human cardiac tissue, offering a potential molecular mechanism for sex-specific differences in cardiac remodeling.
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Indicates sex-specific estradiol effects on cardiac progesterone receptors; extends mechanistic insights while leaving clinical implications open.
BACKGROUND: Although circulating levels of sexual hormones in elderly men and women are low and quite similar, the adaptation of the elderly heart to stress differs between the sexes. We have hypothesized that the effects of sexual hormones in the heart may differ in men and women. Here, we assessed whether 17β-oestradiol regulates gene expression in the human heart in a sex-dependent manner. We selected the progesterone receptor as a well studied 17β-oestradiol target that may be pathologically linked to cardiac remodelling. METHODS: In order to assess the ex vivo effects of 17β-oestradiol in intact human cardiac tissues, we developed a 24-h model for the culture of human atrial myocardium. We verified tissue viability after 24 h in culture with two standard assays to determine the degree of apoptosis and metabolic activity of cardiac tissues. Progesterone receptor mRNA and protein level were measured after 24-h treatment of tissues with 17β-oestradiol. Statistical analysis was performed by the Mann-Whitney U test and two-way ANOVA. RESULTS: We established a tissue culture model that allows for the study of viable human cardiac tissue over a 24-h period. After 24 h, cultured cardiac tissues revealed low apoptosis, retained their metabolic activity and, therefore, remained viable. Treatment with 17β-oestradiol led to an induction of the progesterone receptor mRNA level in female (P = 0.001) but not in male tissues. Similarly, there was an increase in the level of progesterone receptor protein in female tissues (P = 0.03), while a decreasing trend was observed in male tissues (P = 0.079) exposed to 17β-oestradiol. CONCLUSIONS: Our novel finding may offer a molecular explanation for the sex-specific differences observed in cardiac remodelling. The culture model we established for human cardiac tissue will facilitate the study of cellular processes in health and disease and will be of use for pharmacological testing.
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Kararigas et al. (2010) studied Coronary artery disease (undergoing coronary bypass surgery) (n=21). 17 beta-oestradiol (E2) vs. 10^-8 M 2-hydroxypropyl-beta-cyclodextrin (HBC) was evaluated on Progesterone receptor (PGR) mRNA expression level in female tissues (1.36-fold increase, p=0.001). 17 beta-oestradiol treatment significantly increased progesterone receptor mRNA by 1.36-fold (P=0.001) and protein levels by 1.40-fold (P=0.03) in female human cardiac tissues, but had no effect in male tissues.
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