Insulin-Like Growth Factor-I and -II in Human Benign Prostatic Hyperplasia: Relationship with Binding Proteins 2 and 3 and Androgens

Abstract

In prostatic tissue, androgen action may be mediated by growth factors such as insulin-like growth factor-I (IGF-I) and II (IGF-II), which are mitogenic for prostatic cells and modulate the stroma–epithelium interaction. IGF-binding proteins (IGFBPs) have an autocrine and/or paracrine role in regulating the local actions of the IGFs. In this study, testosterone, dihydrotestosterone (DHT), 3αandrostanediol (3αdiol), IGF-I, IGF-II, IGFBP2, and IGFBP3 concentrations were evaluated in human benign prostatic hyperplasia (BPH) tissue. Samples of prostate tissue were removed by suprapubic prostatectomy from twelve BPH patients. Androgen tissue levels were determined by radioimmunoassay after purification on celite microcolumns. IGF-I, IGFBP2, and IGFBP3 were measured by radioimmunoassay, and IGF-II by immunoradio metric assay, after acidification and chromatography on Sep-pak C18 Cartridges for IGF-I and IGF-II. Androgen concentrations, expressed in ng/g tissue (mean ± SE), were 0.51 ± 0.05 for testosterone, 5.3 ± 0.16 for DHT, and 1.1 ± 0.07 for 3αdiol. IGF-I, IGF-II, IGFBP2, and IGFBP3 levels were 24 ± 3.7, 121 ± 14 ng/g tissue and 0.44 ± 0.05 and 1.2 ± 0.17 μg/g tissue, respectively. No correlation between IGF-I, androgens, and IGFBPs was found. IGF-II was positively correlated with DHT ( r = 0.78; p = 0.003) and 3αdiol ( r = 0.66; p = 0.021) but not with IGFBPs. These data suggest that in BPH, DHT modulates the IGF system by increasing IGF-II without modifying IGFBPs. Therefore, the stroma–epithelium interaction, which plays an important role in prostatic growth, may be regulated by DHT through IGF-II.