Finasteride alters AR receptors in testis/epididymis

Hormonal status of male reproductive system androgens and estrogens in the testis and epididymis

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THE INFLUENCE OF HORMONAL DEFICIENCY AND ENVIRONMENTAL FACTORS ON THE EPIDIDYMIS

As it was shown, morphology and function of epididymis are controlled by androgens and DHT is the most potent androgen in this organ.

This androgen is transported directly from testis in the complex with the androgen binding protein (ABP) and additionally is formed by irreversible conversion of testosterone in epididymal epithelial cells due to the activity of 5α-reductase.

Two isoforms of this enzyme exist in the epididymis, 5α-reductase type 1 and 2, encoded by two independent genes. The latter is preferentially expressed in the epididymis [26].

Finasteride is a potent 5α-reductase inhibitor used for treatment of benign prostate hypertrophy [26]. In men receiving finasteride for a long time because of androgenetic alopecia [27], the morphology of the male reproductive system organs is expected to be normal, as sexual function of the patients remained stable.

In contrast, although the morphology of testes in rats treated with finasteride during the time of two seminiferous Androgens and estrogens in the male reproductive tract 53 epithelium cycles (28 days) is normal, the prolonged treatment with finasteride through the time of total spermatogenesis (56days) leads to alterations in the morphology of the testes.

DHT deficiency results in sloughing of immature germ cells, namely late pachytene spermatocytes and spermatids in different developmental steps.

Interestingly, the treatment of the rats with finasteride does not affect the morphology of the epididymis. However, it is possible that a lower number of spermatozoa in the lumen of the epididymis of finasteride-treated rats during 56 days reflects the morphological status of seminiferous tubules [29].

Pharmacologically-induced DHT deficiency also produces alterations in the expression of steroid receptors in rat epididymis. After 28-day-treatment with finasteride a significant decrease in the intensity of nuclear immunostainings of AR, ERα and ERβ in the epididymal epithelial cells was observed, while 56-day-treatment with finasteride causes alterations in the distribution of the receptors, from nuclear to cytoplasmic immunolocalization [58].

Altered expression and distribution of steroid hormone receptors may reflect the hormonal status within the epididymis.