Estrogen and the cardiovascular system

Molecular and Cellular Cardiology, Department of Medicine, University of California, Davis, CA 95616, USA.
Pharmacology [?] Therapeutics (Impact Factor: 7.75). 03/2012; 135(1):54-70. DOI: 10.1016/j.pharmthera.2012.03.007
Source: PubMed

ABSTRACT Estrogen is a potent steroid with pleiotropic effects, which have yet to be fully elucidated. Estrogen has both nuclear and non-nuclear effects. The rapid response to estrogen, which involves a membrane associated estrogen receptor(ER) and is protective, involves signaling through PI3K, Akt, and ERK 1/2. The nuclear response is much slower, as the ER-estrogen complex moves to the nucleus, where it functions as a transcription factor, both activating and repressing gene expression. Several different ERs regulate the specificity of response to estrogen, and appear to have specific effects in cardiac remodeling and the response to injury. However, much remains to be understood about the selectivity of these receptors and their specific effects on gene expression. Basic studies have demonstrated that estrogen treatment prevents apoptosis and necrosis of cardiac and endothelial cells. Estrogen also attenuates pathologic cardiac hypertrophy. Estrogen may have great benefit in aging as an anti-inflammatory agent. However, clinical investigations of estrogen have had mixed results, and not shown the clear-cut benefit of more basic investigations. This can be explained in part by differences in study design: in basic studies estrogen treatment was used immediately or shortly after ovariectomy, while in some key clinical trials, estrogen was given years after menopause. Further basic research into the underlying molecular mechanisms of estrogen's actions is essential to provide a better comprehension of the many properties of this powerful hormone.

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    ABSTRACT: Estrogens, a class of steroid hormones, regulate the growth, development, and physiology of the human reproductive system. Estrogens also involve in the neuroendocrine, skeletal, adipogenesis, and cardiovascular systems. Estrogen signaling pathways are selectively stimulated or inhibited depending on a balance between the activities of estrogen receptor (ER) α or ERβ in target organs. ERs belong to the steroid hormone superfamily of nuclear receptors, which act as transcription factors after binding to estrogen. The gene expression regulation by ERs is to modulate biological activities, such as reproductive organ development, bone modeling, cardiovascular system functioning, metabolism, and behavior in both females and males. Understanding of the general physiological roles of ERs has been gained when estrogen levels were ablated by ovariectomy and then replenished by treatment with exogenous estrogen. This technique is not sufficient to fully determine the exact function of estrogen signaling in general processes in living tissues. However, a transgenic mouse model has been useful to study gene-specific functions. ERα and ERβ have different biological functions, and knockout and transgenic animal models have distinct phenotypes. Analysis of ERα and ERβ function using knockout mouse models has identified the roles of estrogen signaling in general physiologic processes. Although transgenic mouse models do not always produce consistent results, they are the useful for studying the functions of these genes under specific pathological conditions.
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    ABSTRACT: To evaluate the histomorphometry of cardiomyocytes and collagen present in the myocardium of rats treated with a concentrated extract of soy or 17β-estradiol (E2). Twenty-eight rats were divided into four groups: GCtrl - estrus phase; GOvx - ovariectomized (Ovx) and receiving vehicle; GIso - Ovx and treated with soy extract (150 mg/kg per day); GE2 - Ovx and treated with E2 (10 µg/kg per day). The drugs and vehicle (0.2 mL propylene glycol) were administered for 30 consecutive days after ovariectomy. On the last day the animals were anesthetized, the hearts removed, submerged in 10% formaldehyde and fragments of the ventricles underwent histological procedures, and the sections were stained with hematoxylin and eosin or picrosirius-red. Histomorphometric analysis (number and volume of nuclei and quantification of collagen) was performed under a light microscope with AxioVision Rel. 4.2 software, and collagen fibers were quantified using IMAGELAB-2000 software. Data were submitted to ANOVA followed by the Tukey test (p<0.05). We observed a higher number of cardiomyocyte nuclei in animals of the Ovx and Iso groups than in GE2 and GCtrl animals (GOvx=121.7±20.2=GIso=92.8±15.4>GE2=70.5±14,8=GCtrl=66.3±9.6; p <0.05), while the nuclear volume was greater in the Ctrl and E2 groups (GE2=35.7±4.8 GCtrl=29.9±3.6=>GIso=26.5±4.5=GOvx=22.4±2.9; p <0.05). Collagen concentration was higher in the Ovx group (GOvx=5.4±0.1>GCtrl=4.0±0.1=GIso=4.4±0.08=GE2=4.3±0.5; p <0.05). Estrogen may prevent the reduction of the nuclear volume of cardiomyocytes and collagen deposition between heart muscle fibers, while the administration of isoflavones only prevents the deposition of collagen, which can preserve the mechanical properties of cardiac fibers.
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    International journal of cardiology 10/2012; 168(1). DOI:10.1016/j.ijcard.2012.09.049 · 6.18 Impact Factor