RESUMO
We investigated the influence of sex hormones on the expression of α- and ß-cardiac myosin heavy chain isoforms (α-MHC and ß-MHC) in C57bl/6 mice of both sexes under physiological and pathological conditions. In the left ventricles (LVs) of fertile female mice, ß-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 ß-adrenoceptors (ß1-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 ß1- and ß2-ARs abolished sex difference of ß-MHC expression, as mRNA levels in the LVs of knockout males were increased and reached values comparable to those of knockout females. Moreover, the ß1-AR antagonist metoprolol induced about a threefold increase in ß-MHC expression in adult male mice. The capability of gender to regulate ß-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 ß-MHC and a 50% decrease in ß1-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 ß2-AR expression. In conclusion, our results show that the expression of ß-MHC and ß1-AR in the LVs undergo gender-related and correlated changes under both physiological and pathological conditions and suggest a role of ß1-AR-mediated signaling.
