Hormonal regulation of Beta-myosin heavy chain expression in the mouse left ventricle.

We investigated the influence of sex hormones on the expression of ?- and ?-cardiac myosin heavy chain isoforms (?-MHC and ?-MHC) in C57bl/6 mice of both sexes under physiological and pathological conditions. In the left ventricles (LVs) of fertile female mice, ?-MHC expression was tenfold higher compared with the age-matched males, whereas no difference was found in ?-MHC expression. These differences disappeared after ovariectomy or in immature mice. We also found a sex-related difference in expression of ?-adrenoceptors (?1-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 ?1- and ?2-ARs abolished sex difference of ?-MHC expression, as mRNA levels in the LVs of knockout males were increased and reached values comparable to those of knockout females. Moreover, the ?1-AR antagonist metoprolol induced about a threefold increase in ?-MHC expression in adult male mice. The capability of gender to regulate ?-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 ?-MHC and a 50% decrease in ?1-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 ?2-AR expression. In conclusion, our results show that the expression of ?-MHC and ?1-AR in the LVs undergo gender-related and correlated changes under both physiological and pathological conditions and suggest a role of ?1-AR-mediated signaling.