Yandrogens Regulate Connexin26 to Connexin32 Switch in the Epididymis and Ventral Prostate
Résumé
Postnatal epididymal development and differentiation of the epithelium is associated with changes in the expression of connexins 32 (Cx26) and 32 (Cx32). Previous studies have shown that as differentiation of the epithelium progresses, Cx26 mRNA and protein levels decrease while Cx32 levels increase. The switch in expression of Cxs has been reported in several other tissues. What is not known, however, is how these changes occur. Androgens play an important role in regulating the differentiation of the epididymal epithelium. The objective of this study was to determine the interactions between Cx26 and Cx32 during development and the role of androgens in regulating Cx26 and Cx32 in two androgen dependant tissues: the epididymis and the ventral prostate. To determine whether or not loss of Cx26 is important for the regulation of Cx32, epididymal RCE cells were treated with a Cx26 siRNA. While Cx26 mRNA levels were significantly decrease by more than 60% there were no changes in Cx32 mRNA levels. In order to assess the role of androgens in the regulation of Cx32 and Cx26, an in vivo experiment in which rats were either sham operated, orchidectomized or orchidectomized and treated with testosterone. Results indicate that in the caput epididymidis and ventral prostate, Cx26 mRNA levels were increased with orchidectomy and repressed with the addition of testosterone. In contrast, Cx32 levels were decreased with orchidectomy but significant increase by testosterone treatment in both tissues. To further confirm the role of androgens in this regulation, androgen responsive LnCAP cells were cultured with stripped serum and treated with dihydrotestosterone (10nM, DHT) for 24 hrs. The results indicate that DHT significantly decreased levels of Cx26 and increased those of Cx32. Gene promoter analysis indicates that both genes contain a palindromic androgen response element upstream from the transcriptional start site. These results suggest that Cx26 to Cx32 switch is regulated by androgen repression of the Cx26 gene and activation of Cx32. Supported by NSERC.