Regional distribution of epidermal growth factor, testosterone and dihydrotestosterone in benign prostatic hyperplasia tissue

Abstract

In benign prostatic hyperplasia (BPH), basic fibroblast growth factor (bFGF) is found to have a regional distribution, with concentrations in the periurethral zone (where the primitive fibrostromal nodule originates) higher than those of the peripheral subcapsular zone. The aim of the present investigation was to verify whether androgens and epidermal growth factor (EGF) are uniformly distributed from the periurethral to the peripheral zone or whether they show regional differences. Tissue samples, removed by transvesical resection from nine untreated BPH patients, sectioned in periurethral, subcapsular, and intermediate zones, were examined. In the periurethral zone, dihydrotestosterone (DHT), testosterone, and EGF, determined by radioimmunoassay (RIA) techniques after purification on Celite microcolumns and Sep-pak C18 cartridge, showed values significantly higher (mean +/- SD: 1121 +/- 482 pg, 250 +/- 129 pg, and 6.89 +/- 3.28 ng/mg DNA, respectively; P < 0.01) than those of the subcapsular zone (489 +/- 190 pg, 114 +/- 70 pg, and 3.40 +/- 1.90 ng/mg DNA, respectively). A positive linear correlation between EGF, testosterone, and DHT was also observed. The regional distribution of EGF, testosterone, and DHT was similar to that found for bFGF: the highest levels of these factors in the periurethral region allow us to hypothesize on their possible involvement in the rewakening of mesenchymal tissue, leading to the formation of the primitive fibrostromal nodule and then to BPH development.

Effects of long-term treatment withSerenoa repens (Permixon®) on the concentrations and regional distribution of androgens and epidermal growth factor in benign prostatic hyperplasia

“…These results confirm the androgen-dependence of the production of this growth factor, that, in the untreated group, presents a positive linear correlation with tissue DHT (r = 0.658, P < 0.001) and T (r = 0.450, P < 0.01) [21]. This fall in EGF levels may be also due to a competitive inhibition of the binding of residual DHT to the androgen receptors, which is the other possible mechanism of action of Serenoa repens demonstrated by in vitro studies on rat prostatic cells [1][2][3][4][5].…”

“…This finding is of particular interest if we consider that in BPH tissue the two androgens and EGF present regional variations in their distribution, the highest levels being in the zone adjacent to the urethra, where the primitive nodule originates and where the successive growth processes lead to compression of the urethra, with reduction of urinary flow [6,21].…”

“…Prostatic specimens, removed by suprapubic prostatectomy, were sectioned in three regions, i.e., periurethral, subcapsular, and intermediate, as previously described [21]. Each prostate was sectioned on a frontal plane parallel to the urethra, in front of and behind it; the remaining tissue, represented by the two lateral portions of the gland, was cut along the sagittal plane, parallel to the urethra, into sections of 0.6 cm; the most internal was the periurethral region, the outermost was the subcapsular region, and the one included between these two was the intermediate region.…”

Over-expression of epidermal growth factor receptor and c-erbB2/neu but not ofint-2 genes in benign prostatic hyperplasia by means of semi-quantitative PCR

“…Indeed, increased signal transduction through EGFr can lead to abnormal cell growth; over-expression of EGFr in vitro has oncogenic potential, and its immunohistochemical over-expression has been reported in BPH and correlated with epithelial cell numbers (Ching et al, 1993;Lubrano et al, 1993;Myers et al, 1993;Giri et al, 1995;Sciarra et al, 1995;Dahiya et al, 1996;De Bellis et al, 1996). Because the over-expression of a gene might be a direct consequence of the presence of several copies of this gene in the genome, besides analyzing the expression levels of EGFr, c-erbB2/ neu and int-2 genes, we also investigated their amplification status in patients with BPH and in normal prostate tissues from organ donors.…”

“…Others, also using immunohistochemical methods, have identified increased levels of EGFr (Mellon et al, 1992;Lubrano et al, 1993;Myers et al, 1993) and of c-erbB2/neu (Mellon et al, 1992) in prostatic adenocarcinoma samples and in BPH, in which overexpression of EGFr and c-erbB2/neu is restricted to epithelial cells (Giri et al, 1995;De Bellis et al, 1996). Over-expression of mRNA levels for EGFr and its ligands, epidermal growth factor and transforming growth factor alpha has also been observed in BPH and cell lines (Ching et al, 1993;Sciarra et al, 1995;Dahiya et al, 1996). However, although the status of EGFr and c-erbB2 gene amplification has not been analyzed in any of the above reports, no amplification has been detected in prostate cancer by others (Latil et al, 1994;Fournier et al, 1995).…”