Testosterone modulation of cardiac β-adrenergic signals in a rat model of heart failure.

Abstract

In this study, we examined the effects of castration and testosterone replacement on β-adrenoceptor and G protein expression in rats subjected to doxorubicin-induced heart failure. Five groups were included in this report: control, sham-castration with heart failure, castration with heart failure, castration+testosterone replacement with heart failure and castration+testosterone replacement and flutamide with heart failure. At 4 weeks post-treatment, echocardiography, hemodynamics and histopathology were assessed. Castration led to a further deterioration in myocardial performance, apoptosis and fibrosis, while testosterone replacement ameliorated these effects. Data obtained from Western blots revealed that testosterone upregulated the expression of β(2)-adrenoceptor, Gs, Gi(2) and bcl2 levels, downregulated the expression of β(3)-adrenoceptor, Gi(3) and GRK2 levels, and did not modify the expression of β(1)-adrenoceptor levels in the hearts of castrated rats subjected to doxorubicin-induced heart failure. Analyses of serum 17β-estradiol concentrations test confirmed that these effects of testosterone were exerted through the androgen pathway. Thus our findings suggest that testosterone may have beneficial effects for male heart failure patients with androgen deficiency and this protection involves modulation of the cardiac β-adrenergic system.

• Authors: Junfeng Sun, Lu Fu, Xianling Tang, Ying Han, Dan Ma, Junxian Cao, Ningning Kang, Hongfei Ji
• Journal: General and comparative endocrinology (Gen Comp Endocrinol) Vol. 172 Issue 3 Pg. 518-25 (Jul 01 2011) ISSN: 1095-6840 [Electronic] United States
• PMID: 21549119 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Estrogens
• Proto-Oncogene Proteins c-bcl-2
• Receptors, Adrenergic, beta
• Testosterone
• Flutamide
• Doxorubicin
• Grk2 protein, rat
• G-Protein-Coupled Receptor Kinase 2
• GTP-Binding Proteins

Topics

• Animals
• Apoptosis (drug effects)
• Blotting, Western
• Doxorubicin (pharmacology)
• Echocardiography
• Estrogens (blood)
• Flutamide (pharmacology)
• G-Protein-Coupled Receptor Kinase 2 (genetics, metabolism)
• GTP-Binding Proteins (genetics, metabolism)
• Heart (drug effects)
• Heart Failure (chemically induced, metabolism)
• Hemodynamics
• Male
• Myocardium (pathology)
• Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)
• Rats
• Receptors, Adrenergic, beta (metabolism)
• Signal Transduction (drug effects)
• Testosterone (blood, pharmacology, physiology)