Finasteride treatment alters tissue specific androgen receptor expression in prostate tissues

Abstract

BACKGROUND Normal and pathologic growth of the prostate is dependent on the synthesis of dihydrotestosterone (DHT) from testosterone by 5α-reductase. Finasteride is a selective inhibitor of 5α-reductase 2, one isozyme of 5α-reductase found in abundance in the human prostate. The objective of this study was to investigate the effects of finasteride on androgen receptor expression and tissue morphology in human benign prostatic hyperplasia specimens. METHODS Patients undergoing transurethral resection of the prostate and either treated or not treated with finasteride between 2004 and 2010 at the University of Wisconsin-Hospital were retrospectively identified using an institutional database. Prostate specimens from each patient were triple-stained for androgen receptor, prostate-specific antigen, and basal marker cytokeratin 5. Morphometric analysis was performed using the multispectral imaging, and results were compared between groups of finasteride treated and non-treated patients. RESULTS Epithelial androgen receptor but not stromal androgen receptor expression was significantly lower in patients treated with finasteride than in non-treated patients. Androgen receptor-regulated prostate-specific antigen was not significantly decreased in finasteride-treated patients. Significant luminal epithelial atrophy and basal cell hyperplasia were prevalent in finasteride treated patients. Epithelial androgen receptor expression was highly correlated to the level of luminal epithelial atrophy. CONCLUSIONS In this study, finasteride decreased the expression of epithelial androgen receptor in a tissue specific manner. The correlation between epithelial androgen receptor and the extent of luminal epithelial atrophy suggests that epithelial androgen receptor may be directly regulating the atrophic effects observed with finasteride treatment.

Isolation and analysis of discreet human prostate cellular populations

“…These patients display a wide range of BPH related symptoms, making them good sources of transition zone (TZ) tissue with which to examine the genesis of BPH (Bauman et al, 2014a, Bauman et al, 2014b, Lin-Tsai et al, 2014, Ma et al, 2012, Nicholson et al, 2013). We typically collect 1–3 grams of TZ from these patients, and upon histological evaluation, approximately 50% of the tissues are viable, cancer-free specimens.…”

Hormone concentration, metabolic disorders and immunoexpression of androgen and estrogen-alpha receptors in men with benign prostatic hyperplasia and testosterone deficiency syndrome

“…The recent study of Wen et al [32] showed that androgen receptors located in the prostate stroma may take part in the etiology of BPH. The immunohistochemical analysis of androgen receptors in BPH patients treated with finasteride conducted by Bauman et al [33] suggests that this treatment may decrease the expression of this receptor in the prostate epithelium. Biolchi et al [34] analyzed genotypes and testosterone levels in a group of 126 patients, aged 40 to 60 years, whose prostate volumes exceeded 30 mL.…”

Effect of high-dose finasteride combined with transurethral plasmakinetic resection of prostate on prostatespecific antigen and inflammatory factors in patients with benign prostatic hyperplasia

“…Thus, it was recommended that this drug should be used in the perioperative period. However, the effectiveness of finasteride in BPH treatment is associated with its inhibition of angiogenesis, and negative its effect on local anti-inflammatory agents [8,9]. However there are few reports on the impact of administration of finasteride in the perioperative period on the serum levels of inflammatory factors of patients.…”