title: 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.affiliation: Department of Cardiovascular Medicine, First Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Sun
authors.forename: Lu
authors.initials: L
authors.lastname: Fu
authors.forename: Xianling
authors.initials: X
authors.lastname: Tang
authors.forename: Ying
authors.initials: Y
authors.lastname: Han
authors.forename: Dan
authors.initials: D
authors.lastname: Ma
authors.forename: Junxian
authors.initials: J
authors.lastname: Cao
authors.forename: Ningning
authors.initials: N
authors.lastname: Kang
authors.forename: Hongfei
authors.initials: H
authors.lastname: Ji
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D004317:Doxorubicin / Q000494:pharmacology; D004452:Echocardiography; D004967:Estrogens / Q000097:blood; D005485:Flutamide / Q000494:pharmacology; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000235:genetics / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D006333:Heart Failure / Q000139:chemically induced / Q000378:metabolism*; D006439:Hemodynamics; D008297:Male; D009206:Myocardium / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013739:Testosterone / Q000097:blood / Q000494:pharmacology* / Q000502:physiology
chemical_list: D004967:Estrogens; D019253:Proto-Oncogene Proteins c-bcl-2; D011943:Receptors, Adrenergic, beta; D013739:Testosterone; D005485:Flutamide; D004317:Doxorubicin; C496569:Grk2 protein, rat; D054769:G-Protein-Coupled Receptor Kinase 2; D019204:GTP-Binding Proteins