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

Abstract

Estrogens have significant direct and indirect effects on prostate gland development and homeostasis and have been long suspected in playing a role in the etiology of prostatic diseases. Direct effects are mediated through prostatic estrogen receptors alpha (ERalpha) and beta (ERbeta) with expression levels changing over time and with disease progression. The present review examines the evidence for a role of estrogens and specific estrogen receptors in prostate growth, differentiation and disease states including prostatitis, benign prostatic hyperplasia (BPH) and cancer and discusses potential therapeutic strategies for growth regulation via these pathways.

Figure 1

A. Modular Structure of Estrogen Receptor. The large gene (>70 Kb) is transcribed into mRNA with 9 exons that encode for a protein with five distinct functional domains referred to as the A/B domain (transactivational), C domain (DNA binding), D domain (hinge region), E domain (ligand binding) and F domain. B. Comparison of the domain structures of ERα and ERβ. The degree of homology for the separate functional domains are indicated at the bottom.

Figure 2

A. Incidence of wild-type and βERKO mice presenting with T-cell infiltration within the prostatic complex of at one year of age. T-cell infiltration throughout the prostatic complex was blindly scored as 0 (absent), 1 (rare), 2 (focal), 3 (abundant) and 4 (massive) for the two genotypes. Overall incidences between the genotypes was shown to be significant at P < 0.005 using a Chi-square test for trend. B. Inflammatory cell infiltration in the ventral prostate lobes of wild-type (with 0 and 2 Score) and βERKO (with 3 and 4 Score) mice at 1 year of age. Wild-type prostates were either free of lymphoid infiltration (0) or contained rare or focal (2) T-cell infiltration. In contrast, focal, abundant (3) and massive (4) stromal lymphocytic infiltrate were routinely observed in the βERKO prostates. As infiltration became abundant, evidence for diapadesis in the epithelium was observed (arrows). In several instances, lymphoid aggregates were associated with reactive, proliferative epithelium in the immediate vicinity (arrowheads). Magnification = 40×.