title: Effect of estrogen on calcium-handling proteins, beta-adrenergic receptors, and function in rat heart.
abstract: Regulation of cellular Ca(2+) cycling is central to myocardial contractile function. Loss of Ca(2+) regulation is associated with cardiac dysfunction and pathology. Estrogen has been shown to modify contractile function and to confer cardioprotection. Therefore, we investigated the effect of estrogen on expression of rat heart myocardial Ca(2+)-handling proteins and beta-adrenergic receptor (beta(1)-AR) and examined functional correlates. Female rats were sham-operated (SHAM) or ovariectomized. Two weeks after ovariectomy rats were injected (i.p.) daily with estradiol benozoate (OVX+EB) or sesame oil (OVX) for 2 weeks. Protein abundance was measured by immunoblotting and mRNA was quantified by real-time RT-PCR. OVX significantly decreased estrogen and progesterone levels and EB replacement returned both estrogen and progesterone to physiological levels. OVX induced a 75% reduction of uterine weight and a gain in body weight. Replacement restored weights to SHAM level. OVX increased and estrogen-replacement normalized abundance of beta(1)-AR and L-type Ca(2+) channel (Cav1.2) protein. OVX decreased sodium-Ca(2+) exchange protein (NCX) and estrogen restored protein abundance to SHAM levels. Sarcoplasmic reticular ATPase (SERCA), phospholamban (PLB), and ryanodine receptor (RyR) abundance was not altered by hormone status. Levels of mRNA encoding for beta(1)-AR, Cav1.2, and NCX were not influenced by OVX or estrogen replacement. OVX had no effect on SERCA and PLB mRNA level but estrogen replacement elicited a significant increase compared to OVX and SHAM. Estrogen-dependent changes in Ca(2+)-handling proteins and beta(1)-AR are theoretically consistent reduced myocellular Ca(2+) load. However, hormone-dependent alterations in protein were not associated with changes in contractile function.
authors.affiliation: Department of Clinical Nursing Science, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, Korea.
authors.forename: Sang Hui
authors.initials: SH
authors.lastname: Chu
authors.forename: Paul
authors.initials: P
authors.lastname: Goldspink
authors.forename: Jill
authors.initials: J
authors.lastname: Kowalski
authors.forename: Jenny
authors.initials: J
authors.lastname: Beck
authors.forename: Dorie W
authors.initials: DW
authors.lastname: Schwertz
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics; D009200:Myocardial Contraction / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D010210:Papillary Muscles / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D019831:Sodium-Calcium Exchanger / Q000378:metabolism
chemical_list: D020746:Calcium Channels, L-Type; D002135:Calcium-Binding Proteins; D004967:Estrogens; C419385:L-type calcium channel alpha(1C); D008565:Membrane Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D019831:Sodium-Calcium Exchanger; D002118:Calcium