Estrogen in the etiopathogenesis of BPH

Abstract

BACKGROUND While the androgen‐dependence of the prostate gland has long been accepted, the participation of estrogen, mediated via the stroma in the elicitation of benign prostatic hyperplasia (BPH), has only recently been recognized. Its mode of action is still uncertain. METHODS This review first outlines the regulation of gene expression via hormones, growth factors, and other ligands in the coordination of cell growth, differentiation, and function. Focus is next directed to factors particularly involved in phosphorylation of estrogen receptors. Then, the access of sex steroids, especially of estrogen to the cell and to the transduction machinery, is described, preparatory to examining the hypotheses by which this access causes the process of BPH to occur. RESULTS It becomes clear that the necessary phosphorylative activities which transmit signals to nuclear receptors and thence transcription of target genes can be performed by steroids or mimicked by proxy molecules and by cross‐talk between discrete pathways. The character and concentration of the available estrogen are determined by the extent of its biosynthesis, its penetration of the cell, and its subsequent metabolism. In addition, the estrogen affects its own access through stimulation of facilitating peptide hormones, prolactin, and sex hormone‐binding globulin. Finally, the induction of BPH is shown to be determined by the androgen/estrogen ratio and the change in stromal/epithelial balance accompanying aging. CONCLUSIONS Despite a growing knowledge of hormone levels, metabolism, and activities in the prostate, and the variety of processes and factors they affect, our explanation of BPH is still fanciful. Prostate 41:263–274, 1999. © 1999 Wiley‐Liss, Inc.

The association between body size, prostate volume and prostate-specific antigen

“…Our analyses found body size measures associated with a greater prostate size among both biopsy-negative and low-grade cancer cases, and BMI and height were most clearly associated with prostate volume in a secondary analysis that controlled for the other measurements. Estrogens have long been associated with prostate hyperplasia in animal models, 18,19 and estrogen levels increase with obesity through CYP19 (aromatase) conversion of androgens in adipose tissue. Alternatively, growth hormone levels, in part, responsible for attained height also affect insulin-like growth factor (IGF) and IGF-binding protein levels.…”

Dietary soy-phytoestrogens decrease testosterone levels and prostate weight without altering LH, prostate 5alpha-reductase or testicular steroidogenic acute regulatory peptide levels in adult male Sprague-Dawley rats

“…Additionally, we have previously observed a similar pattern of circulating testosterone reduction in animals on the Phyto-600 diet (at approximately 40-50% of Phytofree values) in three independent studies under the same experimental conditions, representing an n of 39 rats per treatment group. Another possible explanation for this finding is that phytoestrogens have the ability to inhibit the aromatase enzyme in peripheral tissues (Kellis & Vickery 1984, Ibrahim & Abul-Hajj 1990, Wang et al 1994) and the apparent protection phytoestrogens have against BPH and PCa may be via the reduction in local estrogen formation since estrogenic agents are known to be mitogenic (vom Saal et al 1997, Griffiths et al 1998, Farnsworth 1999, Shibata et al 2000, Yaono et al 2000.…”

“…However, in the above rodent studies, prostatic parameters were reduced without changes in testosterone levels among the treatment groups (Sharma et al 1992, Landstrom et al 1998. Thus, the mechanisms across species and presumably among rat strains may represent diverse and complex processes by which phytoestrogens protect against certain types of hormone-dependent cancers and BPH (vom Saal et al 1997, Griffiths et al 1998, Farnsworth 1999, Negri-Cesi et al 1999, Shibata et al 2000, Yaono et al 2000.…”

Steroid-sensitive gene-1 is an androgen-regulated gene expressed in prostatic smooth muscle cells in vivo

“…Seventy-five to ninety percent of male estrogen is formed by the peripheral aromatization of testosterone to E 2 and androstenedione to estrone in the adipose tissue. The remaining 10-25% of E 2 and estrone is produced by the testes (Farnsworth 1999). In the rat ventral prostate, estrogen-receptor alpha is localized to stromal cells, both fibroblasts and smooth muscle cells, which are the primary target of estrogens, whereas estrogen-receptor beta is expressed in the luminal epithelial cells (Prins & Birch  5.…”