The Association of Steroid 5-Alpha Reductase Type 2 and Estrogen Receptors in the Prostate

Abstract

Benign prostatic hyperplasia (BPH) continues to remain a significant health problem. Steroid 5α-reductase 2 (SRD5A2) is the predominant enzyme responsible for prostatic development and growth. Our previous study demonstrated that there is an “androgenic to estrogenic switch” when SRD5A2 is absent in the prostate gland. Here we wished to identify if the expression of estrogen receptors (ER) is associated with the level of SRD5A2 in the prostate. The transcript and protein expression levels of ER was determined in prostatic specimens collected from patients who underwent transurethral resection of the prostate. Using databases GTEx (Genotype-Tissue Expression, n=100), TCGA (The Cancer Genome Atlas, n=496), and Single-cell RNA sequencing data from StrandLab.net, the expression of ER was identified and correlated to SRD5A2 in human prostate samples. Transcript and protein levels of SRD5A2, ESR1, and ESR2 in SRD5A2 transfected human prostatic stromal cell line (BHPrS1) and epithelial cell line (BPH1) were compared. ERα and ERβ were found to express variably in both the stroma and epithelium compartments. ERα was dominantly expressed in the myofibroblasts, and ERβ was mainly expressed in the endothelial cells in the prostate. ESR1 was positively correlated with SRD5A2 in human benign and malignant prostate tissues. The expression of ERα both in transcript and protein levels were promoted with the over-expression of SRD5A2 in transfected BHPrS1 cells. Overall, this study demonstrated that the expression of ER is associated with SRD5A2 in the prostate.