Estrogen receptors activate atrial natriuretic peptide in the rat heart

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Abstract
In this study, semiquantitative reverse transcription–PCR analysis showed that estrogen receptor α (ERα) and β (ERβ) mRNAs are developmentally regulated in the rat heart. We found that ERα mRNA was low in all heart chambers of 4-day-old rats, but was elevated in the atria (6- to 18-fold) and ventricles (3- to 4-fold) of adult rats. Western blotting analysis confirmed that these differences were efficiently translated into 67-kDa ERα protein. ERβ mRNA was expressed at its highest level in the left atrium and was 3- to 4-fold lower in other heart chambers of 4-day-old animals. In adult rats ERβ was decreased dramatically in the left atrium (20-fold) and, to a lesser extent in the other heart chambers (2- to 4-fold). Significant ER changes occurred already in the first week after birth. Accordingly, estrogen regulation in cells from neonatal hearts, as reported in several studies, may not correspond to that occurring in fully differentiated adult hearts, because of an altered degree of ER expression. In adult rats, ovariectomy decreases atrial ERα, the atria/body weight ratio, and atrial natriuretic peptide (ANP) transcription. Treatment of ovariectomized rats with 17-β-estradiol (25 μg, 10 days, s.c.) reversed these changes. In addition, there was no effect of ovariectomy and 17-β-estradiol supplementation on systolic blood pressure, but in ovariectomized rats a decreased heart rate followed 17-β-estradiol administration. Similar to the effects on ERα in the atria, ovariectomy lowered plasma ANP levels, and 17-β-estradiol administration restored ANP in the plasma of ovariectomized rats. Changes in plasma ANP correlated with changes in ANP content in the right atrium, as demonstrated by RIA. Increased ANP expression and secretion in response to ERα activation may be a protective mechanism in the heart.