The Effect of Androgen Deprivation on the Expression of Connexin-43 mRNA in the Heart

Connexin-43 (Cx-43) plays axial roles in the propagation of action potentials and contractile coupling in the heart. Down-regulation of Cx-43 in the heart is associated with arrhythmia, dilated cardiomyopathy, and heart failure. To date, no studies have examined the effects of androgen deprivation therapy (ADT)-induced hypogonadism on the expression of Cx-43 in the heart. This study investigated the effects of testosterone deprivation and its replacement with testosterone enanthate on the expression of Cx-43 mRNA and the muscle-specific miRNAs miR-206 and miR-1, as two potential regulators of the Cx-43 protein expression in the ventricular tissue. Accordingly, 21 male Wistar rats were divided into three groups: Ι) Normal control, П) ORX-S: castrated rats serving as animal models for ADT and receiving the sesame oil as a solvent of testosterone enanthate for ten weeks, and Ш) ORX-T: these animals were castrated, receiving testosterone enanthate (25 mg/kg) for ten weeks. The relative expression of Cx-43 mRNA, miR-206, and miR-1 was determined by qRT-PCR. Cx-43 mRNA was found to be decreased in the ORX-S group. The Cx-43 mRNA was up-regulated after the administration of testosterone enanthate. There were no significant changes in miR-206, and miR-1 levels in the ORX-S and ORX-T groups compared to the controls. Our results indicated that testosterone should be regarded as an important factor in the regulation of Cx-43 mRNA expression in the heart, and testosterone deprivation may down-regulate the Cx-43 mRNA expression; however, it doesn’t alter miR-1 and miR-206 levels. These results suggest that ADT-induced hypogonadism may put males at risk for cardiac dysfunctions.