INSULIN-LIKE-GROWTH-FACTOR BINDING-PROTEIN-5 IS ASSOCIATED WITH INVOLUTION OF THE VENTRAL PROSTATE IN CASTRATED AND FINASTERIDE-TREATED RATS

BACKGROUND. Insulin-like growth factor binding protein (IGFBP)-5 has b een proposed as a signal for apoptosis in the ovary. To determine the relationship between IGFBP-5 and apoptosis during regression of the an drogen-deprived prostate, rats were castrated or treated with the 5 al pha-reductase inhibitor finasteride for 4, 9, 14, 21, and 28 days. MET HODS. Ventral prostate tissue was immunostained for IGFBP-5, and apopt otic cells were identified by in situ end-labeling of fragmented DNA ( TUNEL). To compare the distribution of IGFBP-5 with the distribution o f apoptotic cells, mirror-image serial sections of prostate tissues fr om normal and day 4 finasteride-treated rats were examined. RESULTS. I n normal rats, 4 +/- 1% of prostate epithelial cells stained positivel y for IGFBP-5, and 0.1 +/- 0.03% demonstrated DNA fragmentation. IGFBP -5 staining peaked at day 9 with 93 +/- 2% and 64 +/- 13% of epithelia l cells staining positively in castrated and finasteride-treated rats, respectively. In contrast, DNA fragmentation peaked at day 4 in tissu es from both castrated and finasteride-treated rats with 7 +/- 1% and 0.7 +/- 0.3% of epithelial cells, respectively, staining. In the seria l sections, TUNEL and IGFBP-5 staining were not usually expressed in t he same cells. CONCLUSIONS. Prostatic involution involves both program med cell death and inhibition of cell growth. Because of the distribut ion of staining and the delayed expression of IGFBP-5 relative to init iation of apoptosis, we postulate that IGFBP-5 functions as an inhibit or of cell proliferation rather than as a signal for apoptosis. (C) 19 98 Wiley-Liss, Inc.