Estrogen regulates the proliferation and inflammatory expression of primary stromal cell in benign prostatic hyperplasia

Background: To investigate the expression of estrogen receptor (ER) in prostate tissues of benign prostatic hyperplasia (BPH) individuals, and the effects of estrogen regulating the proliferation and inflammatory expressions of primary prostate stromal cells in BPH. Methods: A total of 44 human BPH prostate tissues were collected to explore the expression of ER by immunohistochemistry (IHC). Cell proliferation, mRNA and protein expressions were analyzed in primary prostate stromal cells treated with estrogen or estrogen plus fulvestrant through cell count kit-8 (CCK-8) assay, quantitative real-time polymerase chain reaction (qPCR), IHC and western blot, respectively. Results: Firstly, ERβ was positive, and ERα was negative in the transition zone of prostate among all the 44 individuals with BPH. Secondly, the effects could be partially inhibited by fulvestrant, of estrogen promoting the proliferation of primary prostate stromal cells cultured in dulbecco's modified eagle medium (DMEM) supplemented with 2% fetal bovine serum (FBS). Thirdly, estrogen up-regulates the mRNA levels of C-C chemokine receptor type 3 (CCR3), CD40 ligand (CD 40L), C-X-C motif chemokine ligand 9 (CXCL9) and interleukin 10 (IL10), and down-regulates the mRNA levels of C-C chemokine receptor type 4 (CCR4) and interleukin 17C (IL17C). Then, the protein expressions of CCR3, CCR4, CD40L, IL10 and IL17C are positive, and CXCL9 is negative in the third-generation primary prostate stromal cells. Finally, the effects could be partially inhibited by fulvestrant, of estrogen up-regulating the protein levels of CD40L and IL10. Conclusions: The expressions of ER in human BPH prostate tissues are zone-dependent. Estrogen promoting the proliferation of primary prostate stromal cells cultured in DMEM supplemented with 2% FBS. The expressions of CCR3, CCR4, CD 40L, IL17C, CXCL9 and IL10 are regulated by estrogen in primary prostate stromal cells.