The insulin-like growth factor (IGF) system is involved in the regulation of cell growth. The system involves a network of molecules that includes the IGFs themselves (IGF-I and -II), IGF receptors (types I and II), IGF-binding proteins (IGFBP-1 through -6), and IGFBP proteases. Characterization of this complex system in the prostate has recently been initiated. Prostatic cell lines as well as primary cultures of prostatic epithelial and stromal cells have been analyzed for expression of IGFs, receptors, and IGFBPs. Prostatic epithelial cells and, quite likely, stromal cells as well respond to the mitogenic activity of IGFs via the type I IGF receptor. Prostatic stromal cells synthesize and secrete IGF-II; there is evidence that prostatic cell lines also synthesize IGFs, but this has not been confirmed in primary cultures of prostatic epithelial cells. Prostatic stromal and epithelial cells secrete a number of IGFBPs. The biological impact of some of these IGFBPs on the growth of prostatic cells has been examined, and proteolytic cleavage of IGFBP-3 by prostate-specific antigen (PSA) has been demonstrated. Aberrations in several elements of the IGF system have been observed in stromal cells derived from benign prostatic hyperplasia (BPH). The IGF system may therefore have a part in the etiology of BPH as well as in normal and malignant processes in the prostate.
The insulin-like growth factor (IGF) system is one of great complexity. The two growth factors, IGF-I and IGF-II, which have homology to insulin, interact with three cellular receptors: the type I IGF receptor, the type IX IGF receptor (also known as the mannose-6-phosphate receptor), and the insulin receptor. Interaction of the IGFs with these receptors is modulated by six IGF-binding proteins (IGFBPs), which may also have independent interactions with cells. In turn, proteases modify the ability of the IGF-BPs to interact with the IGFs. The reader is referred to one or more of the many recent reviews that have been written on the IGF system as background for this review, which focuses on the IGF system in the prostate.