Regional variations of insulin-like growth factor I (IGF-I), IGF-II, and receptor type 1 in benign prostatic hyperplasia tissue and their correlationwith intraprostatic androgens

Benign prostatic hyperplasia (BPH) is an androgen-dependent disease; it ori ginates exclusively in the inner prostate, which includes tissue surroundin g the urethra. Stromal-epithelial interaction has a pivotal role in the reg ulation of the development and growth of the prostate, and locally produced peptide growth factors are considered important mediators of this interact ion. Insulin-like growth factor I (IGF-I) and IGF-II, acting mainly through type 1 IGF receptor (IGFR1), have mitogenic and antiapoptotic effects on e pithelial and stromal prostatic cells. In this study the expression of IGF- I, IGF-II, and IGFR1 messenger ribonucleic acid (mRNA), the immunoreactive content of IGF-I (irIGF-I) and IGF-II (irIGF-II) were determined in periure thral, intermediate, and subcapsular regions of BPH tissue to verify their possible regional variation; a correlation to the tissue levels of dihydrot estosterone (DHT) and 3 alpha -androstanediol (3 alpha Diol) was also deter mined to verify their possible androgen dependence. Prostates were removed by suprapubic prostatectomy from 14 BPH patients and sectioned in the periurethral, intermediate, and subcapsular regions. Gene expression of IGF-I, IGF-II, and IGFR1 was evaluated by semiquantitative R T-PCR. using beta -actin as a control. irIGF-I was measured by RIA, and irI GF-II was measured by IRMA after acidification and chromatography on Sep-Pa k C-18 cartridges. DHT and 3 alpha Diol concentrations were evaluated by RI A after extraction and purification on Celite microcolumns. IGF-II and IGFR1, but not IGF-I, mRNA was higher in the periurethral than i n the intermediate (P < 0.05) and subcapsular (P < 0.01) region. Also, pros tatic levels of rIGF-II, expressed as picomoles per g tissue, were higher i n the periurethral (20.84 +/- 1.84) than in the intermediate (14.81 +/- 2.1 1; P < 0.05) and subcapsular (10.88 +/- 1.21; P < 0.001) region. No signifi cant differences were found in irIGF-I content. Considering prostatic andro gen levels, DHT and 3 alpha Diol presented a regional variation, with the h ighest concentrations in the periurethral region. IGF-II mRNA and irIGF-II levels were positively correlated with both DHT and 3 alpha Diol content. These results demonstrate that in BPH tissue a greater IGF-II activity is p resent in the periurethral region, the site of origin ofBPH. Moreover, we c an hypothesize that the tissue androgen content may modulate prostatic prod uction of IGF-II, acting at the transcriptional and probably the posttransc riptional level. Therefore, even though further studies will need to confir m this hypothesis, DHT may increase IGF-II activity, mainly in the periuret hral region, which, in turn, induces, through IGFR1, benign proliferation o f both epithelial and stromal cells, characteristic of BPH.