title: Hormonal regulation of β-myosin heavy chain expression in the mouse left ventricle.
abstract: We investigated the influence of sex hormones on the expression of α- and β-cardiac myosin heavy chain isoforms (α-MHC and β-MHC) in C57bl/6 mice of both sexes under physiological and pathological conditions. In the left ventricles (LVs) of fertile female mice, β-MHC expression was tenfold higher compared with the age-matched males, whereas no difference was found in α-MHC expression. These differences disappeared after ovariectomy or in immature mice. We also found a sex-related difference in expression of β-adrenoceptors (β1-AR), as mRNA levels of this gene were 40% lower in fertile females compared with males of the same age but did not differ in prepubertal or ovariectomized animals. Interestingly, the deletion of both β1- and β2-ARs abolished sex difference of β-MHC expression, as mRNA levels in the LVs of knockout males were increased and reached values comparable to those of knockout females. Moreover, the β1-AR antagonist metoprolol induced about a threefold increase in β-MHC expression in adult male mice. The capability of gender to regulate β-MHC expression was also evaluated in the presence of hemodynamic overload. Thoracic aortic coarctation (TAC) produced cardiac hypertrophy along with a 12-fold increase in β-MHC and a 50% decrease in β1-AR expression in males but not in females, thus abolishing the gender difference observed in sham animals for such genes. By contrast, TAC did not change β2-AR expression. In conclusion, our results show that the expression of β-MHC and β1-AR in the LVs undergo gender-related and correlated changes under both physiological and pathological conditions and suggest a role of β1-AR-mediated signaling.
authors.affiliation: Department of Drug Research and Evaluation, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. mario.patrizio@iss.it
authors.forename: Mario
authors.initials: M
authors.lastname: Patrizio
authors.forename: Marco
authors.initials: M
authors.lastname: Musumeci
authors.forename: Ambra
authors.initials: A
authors.lastname: Piccone
authors.forename: Carla
authors.initials: C
authors.lastname: Raggi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Mattei
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Marano
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D051379:Mice; D018995:Myosin Heavy Chains / Q000378:metabolism*; D010052:Ovariectomy; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D012727:Sex Characteristics; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; C551613:Myh7 protein, mouse; D011943:Receptors, Adrenergic, beta; D018995:Myosin Heavy Chains; D008790:Metoprolol