Prostatic involution in men taking finasteride is associated with elevated levels of insulin-like growth factor-binding proteins (IGFBPs)-2, -4, and -5

Abstract

BACKGROUND Insulin-like growth factor-binding proteins (IGFBPs)-2, -4, and -5 are associated with upregulation of apoptosis in the ovary. The purpose of this study was to assess the roles of IGF-I and IGFBPs during involution of the prostate. Frozen and fixed tissue was collected by transurethral prostatectomy from Caucasian men, aged 52–82 years, scheduled for prostatectomy for benign prostatic hyperplasia, who took either placebo (n = 7) or the 5α-reductase inhibitor finasteride for 6 days to 6 years (n = 15) prior to surgery. METHODS Intraprostatic androgen levels were measured by radioimmunoassay. Tissues were immunostained for IGF-I and IGFBP-2, -3, -4, and -5, and staining was quantitated by computerized image analysis. Serial sections were stained for markers of apoptosis (TUNEL and tissue transglutaminase) and IGFBP-2, -4, or -5. RESULTS IGF-I staining was significantly decreased in the medium-term (18–43 days) treatment group and remained so for the duration of the study (P = 0.026). IGFBP-3 staining was unchanged in the early and medium-term treatment groups; however, a transient earlier rise in the level of this proapoptotic protein cannot be ruled out. The percentage of epithelial cell area staining positively for IGFBP-2 increased significantly, from 1.6 ± 0.5 in the placebo group to 12.0 ± 2.0 (P < 0.0001), and 7.6 ± 1.9 (P = 0.003) in the short (6–13 days) and medium-term treatment groups, respectively. IGFBP-4 staining increased from 2.2 ± 0.6 to 9.8 ± 1.9 (P < 0.0001) and 7.4 ± 1.2 (P = 0.004) in the short and medium-term groups, respectively, and IGFBP-5 staining increased from 0.2 ± 0.1 to 3.8 ± 2.0 (P = 0.004) in the medium-term group. The results from serial sections showed that IGFBP-2 and -4 costained with markers of apoptosis, while IGFBP-5 did not. CONCLUSIONS These results indicate that IGFBP-2, -4, and -5 are associated with prostatic involution. Because of the timing and distribution of expression, we hypothesize that IGFBP-2 and -4 have a role as signals for apoptosis, but that IGFBP-5 likely does not. Prostate 42:203–210, 2000. © 2000 Wiley-Liss, Inc.