We investigated the influence of sex-hormones on the expression of a- and b-cardiac myosin heavy chain isoforms (a-MHC and b-MHC) in C57bl/6 mice of both sexes, under physiological and pathological conditions. In the left ventricles of fertile female mice, b-MHC expression were 10 fold higher compared to the age-matched males, whereas no differences were found in the a-MHC expression. These differences disappeared after ovariectomy or in sexually immature mice. We also found a sex-related difference in expression of b1-adrenoceptors (b1-AR), since mRNA levels of this gene were 40% lower in fertile females compared to males of the same age, but did not differ in prepuberal or ovariectomized animals. Interestingly, the deletion of both b1- and b2-AR abolished sex difference in the b-MHC expression , since mRNA levels in knockout males were increased and reached values comparable to those of knockout females. Moreover, the b1-AR antagonist metoprolol induced about three-fold increase of b-MHC expression in male mice. The capability of gender to regulate b-MHC expression was also evaluated in the presence of hemodynamic load. Thoracic aortic coarctation (TAC) produced cardiac hypertrophy along with a 12 fold increase of b-MHC and a 50% decrease of b1AR expression in males but not in females, thus abolishing the gender difference observed in sham animals for such genes. In conclusion our results show that the expression of b-MHC and b1-AR in the left ventricles undergo gender-related and correlated changes under both physiological and pathological conditions, and suggest a role of b1-adrenoceptor-mediated signalling.
Hormonal regulation of beta myosin heavy chain expression in the mouse left ventricle
Elisabetta Mattei;
2013
Abstract
We investigated the influence of sex-hormones on the expression of a- and b-cardiac myosin heavy chain isoforms (a-MHC and b-MHC) in C57bl/6 mice of both sexes, under physiological and pathological conditions. In the left ventricles of fertile female mice, b-MHC expression were 10 fold higher compared to the age-matched males, whereas no differences were found in the a-MHC expression. These differences disappeared after ovariectomy or in sexually immature mice. We also found a sex-related difference in expression of b1-adrenoceptors (b1-AR), since mRNA levels of this gene were 40% lower in fertile females compared to males of the same age, but did not differ in prepuberal or ovariectomized animals. Interestingly, the deletion of both b1- and b2-AR abolished sex difference in the b-MHC expression , since mRNA levels in knockout males were increased and reached values comparable to those of knockout females. Moreover, the b1-AR antagonist metoprolol induced about three-fold increase of b-MHC expression in male mice. The capability of gender to regulate b-MHC expression was also evaluated in the presence of hemodynamic load. Thoracic aortic coarctation (TAC) produced cardiac hypertrophy along with a 12 fold increase of b-MHC and a 50% decrease of b1AR expression in males but not in females, thus abolishing the gender difference observed in sham animals for such genes. In conclusion our results show that the expression of b-MHC and b1-AR in the left ventricles undergo gender-related and correlated changes under both physiological and pathological conditions, and suggest a role of b1-adrenoceptor-mediated signalling.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
