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

Abstract

Connexin-43 (Cx-43) plays axial roles in the propagation of action potentials and contractile coupling in heart. Down-regulation of Cx-43 in 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 heart. This study investigated the effects of testosterone deprivation and its replacement with testosterone on the expression of Cx-43 mRNA and 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 10 weeks, and Ш) ORX-T: these animals were castrated, receiving testosterone enanthate (25 mg/kg) for 10 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 when compared to the controls. Our results indicated that testosterone should be regarded as an important factor in the regulation of the Cx-43 mRNA expression in 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.

Keywords

• connexin-43
• mir-206
• mir-1
• heart
• testosterone
• androgen deprivation therapy