Cardioprotection by Low-dose of Estrogen and Testosterone at the Physiological Ratio on Ovariectomized Rats During Ischemia/Reperfusion Injury

Abstract

Although estrogen and testosterone deficiency have often been associated with the development of cardiac diseases in postmenopausal women, the benefits of estrogen or testosterone therapy are controversial. Supplementation with high dose of estrogen or testosterone alone has been associated with many side effects, especially estrogen. This study was aimed to investigate whether supplementation of testosterone in combination with low-dose estrogen conferred stronger cardioprotective effects on ovariectomized rats subjected to ischemia/reperfusion injury. Female Sprague Dawley rats were subjected to sham operation (Sham) or bilateral ovariectomy (OVX). Two weeks after ovariectomy, OVX rats were treated with one of the following: (1) vehicle (OVX), (2) testosterone (100 μg·kg·d) (OVX+T), (3) estrogen (20 μg·kg·d) (OVX+E), (4) testosterone (100 μg·kg·d) + estrogen (20 μg·kg·d) (OVX+T+E) for 4 weeks. The hearts were mounted on the Langendorff apparatus and subjected to ischemia/reperfusion injury subsequent to the determination of hemodynamic parameters. We examined the release of lactate dehydrogenase, serum estrogen, and testosterone levels and the expression of pAkt/Akt and bax/bcl-2. Testosterone supplementation alone improved the heart function, increased p-Akt/Akt and bcl-2 expression, and decreased the release of lactate dehydrogenase. Accordingly, these effects of testosterone were more pronounced when low-dose estrogen was administered simultaneously, whereas estrogen alone at the dose of the experiment had no significant effects. These effects might be partially orchestrated by the Akt signaling pathway.

Estrogen and calcium handling proteins: new discoveries and mechanisms in cardiovascular diseases

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Estrogen–gut microbiome axis: Physiological and clinical implications

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“…It is widely accepted that estrogen plays a significant role in many disease states including gynecologic conditions and cancers in addition to less obvious estrogen-mediated diseases such as metabolic syndrome ( Fig. 1) [12][13][14][15][16][17]. This review will demonstrate the influence the gut microbiome has on estrogen, and therefore estrogen-mediated disease, and related health outcomes (Fig.…”

Sex Differences in Autophagy Contribute to Female Vulnerability in Alzheimer's Disease

“…Expression of ERβ (Hsieh et al, 2015 ) and GPER (Wang et al, 2017 ) also reduced autophagy and apoptosis via PI3K pathway activation. Less information is available on the effects of testosterone, but there is data to suggest that it also modulates the PI3K response following injury (Huang et al, 2010 ; Fu et al, 2017 ). In addition, estradiol can regulate autophagy through interaction with adenosine monophosphate-activated protein kinase (AMPK).…”