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Updated: Sep 24, 2025

Ovariectomy and 17β-estradiol Replacement in Rats and Mice: A Visual Demonstration
Published on: June 7, 2012
Selective estrogen receptor α and β antagonist aggravate cardiovascular dysfunction in type 2 diabetic ovariectomized
Hossein Azizian1, Zeinab Farhadi2, Mohammad Khaksari3
1Department of Physiology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Objectives:
Type 2 diabetes (T2D) is a major risk factor for cardiovascular disorders (CVD), characterized by pathological diastolic as well as systolic dysfunction, ventricular dilation, and cardiomyocyte hypertrophy. CVD is the main cause of death in postmenopausal women. Estradiol (E2) has protective effects on cardiovascular function. The biological effects of E2 are mainly mediated by classical estrogen receptors (ERs). The present study aimed to investigate the cardioprotective effects of classical ERs in ovariectomized (OVX) diabetic female rats.
Methods:
T2D was induced in female rats by high-fat diet feeding along with a low dose of streptozotocin. Then diabetic animals were divided into eight groups: Sham-control, OVX, OVX + Vehicle (Veh), OVX + E2, OVX + E2 + MPP (ERα antagonist), OVX + E2 + PHTPP (ERβ antagonist), OVX + E2 + Veh, OVX + E2 + MPP + PHTPP. Animals received E2, MPP, and PHTPP every four days for 28 days. At the end blood was collected, serum separated, and used for biochemical parameters. Heart tissue was used for cardiac angiotensin II and cytokines measurement.
Results:
E2 treatment improved the metabolic disorders caused by T2D, and its receptor antagonists intensified the effects of T2D on the metabolic status. Also, E2 therapy decreased cardiac inflammatory cytokines, and MPP and PHTPP increased cardiac inflammation by increasing TNF-α and IL-6 and decreasing IL-10.
Conclusions:
Classical ERs have protective effects on diabetic hearts by improving the metabolic status and inflammatory balance.
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