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 been proposed as a signal for apoptosis in the ovary. To determine the relationship between IGFBP-5 and apoptosis during regression of the androgen-deprived prostate, rats were castrated or treated with the 5alpha-reductase inhibitor finasteride for 4, 9, 14, 21, and 28 days.


METHODS
Ventral prostate tissue was immunostained for IGFBP-5, and apoptotic cells were identified by in situ end-labeling of fragmented DNA (TUNEL). To compare the distribution of IGFBP-5 with the distribution of apoptotic cells, mirror-image serial sections of prostate tissues from normal and day 4 finasteride-treated rats were examined.


RESULTS
In normal rats, 4+/-1% of prostate epithelial cells stained positively 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 epithelial cells staining positively in castrated and finasteride-treated rats, respectively. In contrast, DNA fragmentation peaked at day 4 in tissues from both castrated and finasteride-treated rats with 7+/-1% and 0.7+/-0.3% of epithelial cells, respectively, staining. In the serial sections, TUNEL and IGFBP-5 staining were not usually expressed in the same cells.


CONCLUSIONS
Prostatic involution involves both programmed cell death and inhibition of cell growth. Because of the distribution of staining and the delayed expression of IGFBP-5 relative to initiation of apoptosis, we postulate that IGFBP-5 functions as an inhibitor of cell proliferation rather than as a signal for apoptosis.
Thomas
L N
LN
Department of Medicine and Physiology/Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada.
Cohen
P
P
Douglas
R C
RC
Lazier
C
C
Rittmaster
R S
RS
D000818:Animals; D017209:Apoptosis; D053938:DNA Fragmentation; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D018120:Finasteride / Q000494:pharmacology*; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000032:analysis / Q000378:metabolism*; D008297:Male; D009919:Orchiectomy; D011467:Prostate / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values
D018975:Insulin-Like Growth Factor Binding Protein 5; D018120:Finasteride