Higher Aromatase Expression In Female Heart May Underline Its High Estrogen Content Resulting In Cardioprotection

Abstract

Estrogen (E2) is a well-known cardioprotective steroid hormone. Although heart has all the machinery to biosynthesize estrogen from testosterone by cytochrome P450 aromatase, little is known about the role of local heart E2 concentration [E2] in cardioprotection. We hypothesized that high heart [E2] in females could be one mechanism for the higher cardioprotection in females. We optimized the radioimmunoassay technique to measure heart [E2] in whole homogenate by diethyl ether extraction. Male mouse hearts have significantly higher E2 levels (35±3 pg/ml, n=6) than plasma (12±0.9 pg/ml, n=5). Heart [E2] in female mice at estrus and diestrus (diestrus 20.2±1.5 pg/ml n=4; estrus 17.2±0.9 pg/ml, n=4) were very similar to plasma [E2]. Interestingly, in the proestrus stage, heart [E2] was extremely high ∼ 170±4 pg/ml, almost 3 times higher than plasma [E2]. The final heart [E2] will depend on the testosterone level as well as the efficiency of the aromatase to convert testosterone to E2. As females have much lower levels of testosterone (∼40pg/ml at estrus and diestrus and ∼240 pg/ml in proestrus) compared to males (2 ng/ml), much higher heart [E2] in females at proestrus compared to male lead us to hypothesize that the aromatase expression/activity is much higher in females than males. We performed real time PCR and western blot analysis to quantify transcript and protein levels of aromatase in male and in female mice at estrus stage, as this stage is under the control of the preceding estrogen peak at proestrus. Aromatase transcript levels were similar in males and females at estrus, but aromatase protein levels were two fold higher in estrus compared to male. We speculate higher aromatase expression in females may underline its high estrogen content, thus resulting in cardioprotection.