This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pedram, A. Articles by Levin, E. R. Search for Related Content PubMed PubMed Citation Articles by Pedram, A. Articles by Levin, E. R.

Estrogen Inhibits Cardiac Hypertrophy: Role of Estrogen Receptor-β to Inhibit Calcineurin

Department of Medicine (M.R., E.R.L.), Veteran’s Affairs Medical Center Long Beach, Long Beach, California 90822; Department of Medicine (A.P., M.V., E.R.L.), University of California, Irvine, Irvine, California 92697; and Department of Biochemistry (D.L., J.L.), University of Missouri, Columbia, Missouri 65211

Address all correspondence and requests for reprints to: Ellis R. Levin M.D., Medical Service (111-I), Long Beach Veteran’s Affairs Medical Center/University of California-Irvine, 5901 East 7th Street, Long Beach, California 90822. E-mail: ellis.levin{at}va.gov.

Estrogen has been reported to prevent development of cardiac hypertrophy in female rodent models and in humans. However, the mechanisms of sex steroid action are incompletely understood. We determined the cellular effects by which 17β-estradiol (E2) inhibits angiotensin II (AngII)-induced cardiac hypertrophy in vivo. Two weeks of angiotensin infusion in female mice resulted in marked hypertrophy of the left ventricle, exacerbated by the loss of ovarian steroid hormones from oophorectomy. Hypertrophy was 51% reversed by the administration of E2 (insertion of 0.1 mg/21-d-release tablets). The effects of E2 were mainly mediated by the estrogen receptor (ER) β-isoform, because E2 had little effect in ERβ-null mice but comparably inhibited AngII-induced hypertrophy in wild-type or ER-null mice. AngII induced a switch of myosin heavy chain production from to β, but this was inhibited by E2 via ERβ. AngII-induced ERK activation was also inhibited by E2 through the β-receptor. E2 stimulated brain natriuretic peptide protein expression and substantially prevented ventricular interstitial cardiac fibrosis (collagen deposition) as induced by AngII. Importantly, E2 inhibited calcineurin activity that was stimulated by AngII, related to E2 stimulating the modulatory calcineurin-interacting protein (MCIP) 1 gene and protein expression. E2 acting mainly through ERβ mitigates the important signaling by AngII that produces cardiac hypertrophy and fibrosis in female mice.

This article has been cited by other articles:

				E. R. Levin Membrane oestrogen receptor \#945; signalling to cell functions J. Physiol., November 1, 2009; 587(21): 5019 - 5023. [Abstract] [Full Text] [PDF]

				E. R. Levin Rapid signaling by steroid receptors Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2008; 295(5): R1425 - R1430. [Abstract] [Full Text] [PDF]