Histological localization of estrogen receptors in normal and diseased human prostates by immunocytochemistry

Abstract

The role of estrogens and estrogen receptors (ER) in the human prostate remains unresolved. In this study we have used the monoclonal ER antibody H222 to investigate the histological localization of ER in normal and diseased human prostates by immunocytochemistry. Prostate tissue was obtained from 3 young organ donors (Group I-normal prostate), from 14 prostates removed by radical prostatectomy or radical cystoprostatectomy, which had caused no or only mild obstructive symptoms (Group II-non-obstructive prostate), and from 11 prostates removed by suprapubic prostatectomy, which had caused severe obstructive symptoms due to a large benign prostatic hyperplasia (BPH) (Group III-obstructive prostate). In prostates of all groups ER were found to be in nuclei of the prostatic urethra and of the periurethral prostatic duct. In striking contrast, ER in the interglandular prostatic stroma was not as homogeneous among the different groups. We observed a low concentration of ER in the stroma of normal prostates, the highest concentration in non-malignant stroma of non-obstructive prostates, and no ER at all in stroma of obstructive prostates. Based on the immunocytochemical localization of ER in normal and diseased human prostate, our results indicate that stromal growth in obstructive BPH may not be mediated via ER. However, we cannot exclude that an increase of stromal ER concentration (as observed in non-obstructive prostates) is directly involved in induction of BPH, leading further prostate growth thereafter into an estrogen independent state.

A role for epithelial-mesenchymal transition in the etiology of benign prostatic hyperplasia

“…ER␤1 is the predominant ER subtype, expressed in the majority of the epithelial as well as the stromal cells whereas ER␣ is found in the stroma of peripheral zone (PZ) but not the transitional zone (TZ) (32). Some studies report an increase in estradiol within BPH tissue (13) and ER␣ has been suggested to mediate stromal proliferation in BPH (33). In the present study we observed expression of ER␤1, but not ER␣ in epithelial and stromal cells.…”

The role of estrogens and estrogen receptors in normal prostate growth and disease

“…In humans, there is evidence for an increased accumulation of estradiol in nuclei of stromal cells in BPH specimens [80] suggesting that elevated ERα in stromal cells may be involved in the etiology of BPH. Of interest, epithelial cells in prostatic periurethral ducts have also been found to consistently express ERα in both normal and BPH tissue [70]. Since this is the prostatic region which forms BPH, it is possible that epithelial ERα in that specific region are involved.…”

“…ERα is localized primarily to the stromal cells of the adult prostate gland in man, dogs, monkeys and rodents [70][71][72][73][74]. Immunohistochemical analysis reveals, however, that ERα expression is heterogeneous in stromal cells, i.e.…”

Endocrine disruptors and prostate cancer risk

“…In addition to androgens, estrogen involvement in the etiology of BPH and prostatic cancer has been postulated and the use of anti-estrogens has been recently recognized to have a therapeutic role in prostate cancer management (Prins & Korach 2008, Raghow et al 2002, Steiner & Pound 2003, Smith et al 2008. Human and rodent prostates express both estrogen receptor a (ERa) and ERb during development and into adulthood with ERa primarily found in stromal cells (Schulze & Claus 1990, Prins & Birch 1997 and ERb in differentiated epithelium (Enmark et al 1997, Prins et al 1998. Furthermore, it is believed that early prostatic developmental events which are regulated by steroids may be linked to the predisposition of this structure to high rates of disease in adult men (Henderson et al 1988(Henderson et al , 1991.…”