title: Single acute stress-induced progesterone and ovariectomy alter cardiomyocyte contractile function in female rats.
abstract: OBJECTIVE
  To assess how ovarian-derived sex hormones (in particular progesterone) modify the effects of single acute stress on the mechanical and biochemical properties of left ventricular cardiomyocytes in the rat.
  
  
  METHODS
  Non-ovariectomized (control, n=8) and ovariectomized (OVX, n=8) female rats were kept under normal conditions or were exposed to stress (control-S, n=8 and OVX-S, n=8). Serum progesterone levels were measured using a chemiluminescent immunoassay. Left ventricular myocardial samples were used for isometric force measurements and protein analysis. Ca(2+)-dependent active force (Factive), Ca(2+)-independent passive force (Fpassive), and Ca(2+)-sensitivity of force production were determined in single, mechanically isolated, permeabilized cardiomyocytes. Stress- and ovariectomy-induced alterations in myofilament proteins (myosin-binding protein C [MyBP-C], troponin I [TnI], and titin) were analyzed by sodium dodecyl sulfate gel electrophoresis using protein and phosphoprotein stainings.
  
  
  RESULTS
  Serum progesterone levels were significantly increased in stressed rats (control-S, 35.6±4.8 ng/mL and OVX-S, 21.9±4.0 ng/mL) compared to control (10±2.9 ng/mL) and OVX (2.8±0.5 ng/mL) groups. Factive was higher in the OVX groups (OVX, 25.9±3.4 kN/m(2) and OVX-S, 26.3±3.0 kN/m(2)) than in control groups (control, 16.4±1.2 kN/m(2) and control-S, 14.4±0.9 kN/m(2)). Regarding the potential molecular mechanisms, Factive correlated with MyBP-C phosphorylation, while myofilament Ca(2+)-sensitivity inversely correlated with serum progesterone levels when the mean values were plotted for all animal groups. Fpassive was unaffected by any treatment.
  
  
  CONCLUSIONS
  Stress increases ovary-independent synthesis and release of progesterone, which may regulate Ca(2+)-sensitivity of force production in left ventricular cardiomyocytes. Stress and female hormones differently alter Ca(2+)-dependent cardiomyocyte contractile force production, which may have pathophysiological importance during stress conditions affecting postmenopausal women.
authors.forename: Judit
authors.initials: J
authors.lastname: Kalász
authors.forename: Enikő Pásztor
authors.initials: EP
authors.lastname: Tóth
authors.forename: Beáta
authors.initials: B
authors.lastname: Bódi
authors.forename: Miklós
authors.initials: M
authors.lastname: Fagyas
authors.forename: Attila
authors.initials: A
authors.lastname: Tóth
authors.forename: Bhattoa Harjit
authors.initials: BH
authors.lastname: Pal
authors.forename: Sandor G
authors.initials: SG
authors.lastname: Vari
authors.forename: Marta
authors.initials: M
authors.lastname: Balog
authors.forename: Senka
authors.initials: S
authors.lastname: Blažetić
authors.forename: Marija
authors.initials: M
authors.lastname: Heffer
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Papp
authors.affiliation: Attila Borbély, University of Debrecen, Institute of Cardiology, Division of Clinical Physiology, Móricz Zsigmond krt. 22, H-4032 Debrecen, Hungary, borbelya@med.unideb.hu.
authors.forename: Attila
authors.initials: A
authors.lastname: Borbély
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004967:Estrogens / Q000097:blood*; D005260:Female; D006352:Heart Ventricles; D006801:Humans; D008163:Luminescent Measurements; D032383:Myocytes, Cardiac / Q000502:physiology*; D010052:Ovariectomy; D010053:Ovary / Q000502:physiology*; D010766:Phosphorylation; D011374:Progesterone / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological; D019210:Troponin I / Q000378:metabolism; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D004967:Estrogens; D011374:Progesterone; D019210:Troponin I; D000099163:Myosin Binding Protein C