Insulin-like growth factor-I (IGF-I) and its binding protein IGFBP-4 in human prostatic hyperplastic tissue: gene expression and its cellular localization.

It has been previously reported that 1) type I insulin-like growth factor (IGF) receptors are present in the human prostatic tissue; 2) IGF-I receptors are mainly localized in the epithelial cells; 3) IGF-I is a mitogen for prostatic epithelial cells in culture; and 4) IGF-binding proteins (IGFBPs) are released by these cells in the conditioned medium. To add information on the mechanism of IGF-I action in the human prostate, we studied the expression and cellular localization of mRNA encoding IGF-I and IGFBP-4 in human prostatic hyperplastic (BPH) tissue. Northern analysis of total RNA extracted from BPH tissues with cDNA probes containing the entire coding regions for IGF-I and IGFBP-4 documented the presence of multiple IGF-I mRNA transcripts with lengths of 7.5, 1.7, 1.3, and 1.1 kilobases and a single 2.1-kilobase transcript of IGFBP-4 mRNA. In situ hybridization with the cDNA probes used for Northern analysis and with cRNA probes synthesized from the respective cDNA demonstrated that IGF-I mRNA was only localized in the stromal cells, whereas IGFBP-4 mRNA was predominantly expressed by epithelial cells. In addition, immunoreactive IGF-I was measured in BPH tissue extracts after acidification and reverse phase chromatography. The mean (+/- SD) IGF-I content of six BPH tissues was 28.1 +/- 4.0 ng/g tissue. Our results suggest that in the human prostate, the locally secreted IGF-I exerts its principal biological effects with a paracrine mode of action and demonstrate that IGFBP-4 is mainly expressed by IGF-I target cells.