THE INSULIN-LIKE GROWTH-FACTOR SYSTEM IN THE PROSTATE

The insulin-like growth factor (IGF) system is involved in the regulat ion of cell growth. The system involves a network of molecules that in cludes 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 b een initiated. Prostatic cell lines as well as primary cultures of pro static 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 IGF s via the type I IGF receptor. Prostatic stromal cells synthesize and secrete IGF-II; there is evidence that prostatic cell lines also synth esize IGFs, but this has not been confirmed in primary cultures of pro static epithelial cells. Prostatic stromal and epithelial cells secret e a number of IGFBPs. The biological impact of some of these IGFBPs on the growth of prostatic cells has been examined, and proteolytic clea vage of IGFBP-3 by prostate-specific antigen (PSA) has been demonstrat ed. Aberrations in several elements of the IGF system have been observ ed in stromal cells derived from benign prostatic hyperplasia (BPH). T he IGF system may therefore have a part in the etiology of BPH as well as in normal and malignant processes in the prostate.