[Epididymis in an experimental model of DHT deficiency: immunolocalization of ERalpha and ERbeta in rat epididymal epithelial cells. In vivo and in vitro studies]

Abstract

Introduction: The aim of this study was to determine the effect of reduced availability of dihydrotestosterone (DHT) on the expression of estrogen receptors alpha and beta (ERalpha and ERbeta) in the epididymis in vivo and in vitro. Expression of estrogen receptors (ERs) is interesting because of the fact that the male reproductive system is controlled not only by androgens but also, in a far-reaching and complex manner, by estrogens. Control by estrogens is exercised through activation of ERs widely distributed in the epididymal epithelium. Epididymal epithelial cells contain a 5alpha-reductase (5alpha-red) which catalyzes the irreversible conversion of testosterone (T) into the most potent and chief androgen of the epididymis, dihydrotestosterone, known to maintain and regulate the structure and functions of the epididymis. Two isoforms of the 5alpha-red were identified: type 1 (5alpha-redl) and type 2 (5alpha-red2). 5alpha-reductase type 2 is more widely expressed in the epididymis than 5alpha-redl. DHT deficit was produced by inhibition of 5alpha-red2 using finasteride (Proscar, MSD Sweden), a steroid inhibitor of this enzyme.

Material and methods: The study was performed in the adult, male Wistar rats randomly divided into control (K) and study (Fin56) groups (5 animals in each). Animals in the study group received 5mg finasteride/kg b.w., orally during 56 days (duration of one spermatogenesis). Immunoexpression of ERs was also studied in epididymal epithelial cells cultured with or without finasteride.

Results: It was shown that DHT deficiency, both in vivo and in vitro condition, modulated ERs expression in comparison to the epididymis from control rats and to epididymal cells cultured without finasteride. Distribution of ERalpha and ERbeta in epididymal cells changed (from nucleus to cytoplasm) and the level of ERs expression was markedly decreased.

Conclusion: The present findings show that the DHT deficiency caused by finasteride altered the expression of ERalpha and ERbeta in the epididymis and possibly may have destabilized the functioning of this organ.