Estrogen receptors activate atrial natriuretic peptide in the rat heart

In this study, semiquantitative reverse transcription-PCR analysis showed t hat estrogen receptor alpha (ER alpha) and beta (ER beta) mRNAs are develop mentally regulated in the rat heart. We found that ER alpha 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 ana lysis confirmed that these differences were efficiently translated into 67- kDa ER alpha protein. ER beta mRNA was expressed at its highest level in th e left atrium and was 3- to 4-fold lower in other heart chambers of 4-day-o ld animals. In adult rats ER beta was decreased dramatically in the left at rium (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 bir th. Accordingly, estrogen regulation in cells from neonatal hearts, as repo rted in several studies, may not correspond to that occurring in fully diff erentiated adult hearts, because of an altered degree of ER expression. In adult rats, ovariectomy decreases atrial ER alpha, the atria/body weight ra tio, and atrial natriuretic peptide (ANP) transcription. Treatment of ovari ectomized rats with 17-beta -estradiol (25 mug, 10 days, s.c.) reversed the se changes. In addition, there was no effect of ovariectomy and 17-beta -es tradiol supplementation on systolic blood pressure, but in ovariectomized r ats a decreased heart rate followed 17-beta -estradiol administration. Simi lar to the effects on ER alpha in the atria, ovariectomy lowered plasma ANP levels, and 17-beta -estradiol administration restored ANP in the plasma o f ovariectomized rats. Changes in plasma ANP correlated with changes in ANP content in the right atrium, as demonstrated by RIA. Increased ANP express ion and secretion in response to ER alpha activation may be a protective me chanism in the heart.