PMID- 9924191 OWN - NLM STAT- MEDLINE DCOM- 19990421 LR - 20190709 IS - 0022-0795 (Print) IS - 0022-0795 (Linking) VI - 160 IP - 2 DP - 1999 Feb TI - Vitamin D analogue EB1089-induced prostate regression is associated with increased gene expression of insulin-like growth factor binding proteins. PG - 223-9 AB - Vitamin D analogues have an antiproliferative effect on prostate cancer cells in vitro and thus have been proposed as candidates for chemoprevention of prostate cancer. Insulin-like growth factor (IGF)-I has been shown to protect cells from apoptosis and plays an essential role in normal prostate physiology. We have studied the effects of the 1,25-dihydroxyvitamin D3 analogue EB1089 on the IGF system in the prostate in vivo. Treatment of rats with EB1089 for 14 days caused a 25% decrease in ventral prostate weight. Apoptosis was detected in prostate sections of EB1089-treated rats by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) assay and histologic examination of hematoxylin/eosin stained tissue sections indicated that secretory epithelial cells were flattened, a characteristic of cells undergoing pressure-induced atrophy. Ventral prostate regression was associated with 15- to 25-fold increases in gene expression of IGF-binding proteins (IGFBPs)-2,-3,-4 and -5. We also observed a 40-fold increase in prostatic IGF-I mRNA levels in response to EB1089. Although we have previously shown that castration of rats leads to upregulation of IGFBPs in the ventral prostate, EB1089 treatment had no effect on serum levels of dihydrotestosterone or free testosterone. These results suggest that prostate regression induced by EB1089 may be related to alterations in availability of IGF-I as a result of increased production of IGFBPs. FAU - Nickerson, T AU - Nickerson T AD - Lady Davis Institute for Medical Research, McGill University, 3755 Cote Ste Catherine Road, Montreal, Quebec, Canada H3T 1E2. FAU - Huynh, H AU - Huynh H LA - eng PT - Journal Article PL - England TA - J Endocrinol JT - The Journal of endocrinology JID - 0375363 RN - 0 (Antineoplastic Agents) RN - 0 (Insulin-Like Growth Factor Binding Protein 2) RN - 0 (Insulin-Like Growth Factor Binding Protein 3) RN - 0 (Insulin-Like Growth Factor Binding Protein 4) RN - 0 (Insulin-Like Growth Factor Binding Protein 5) RN - 0 (Insulin-Like Growth Factor Binding Proteins) RN - 0 (RNA, Messenger) RN - 67763-96-6 (Insulin-Like Growth Factor I) RN - FXC9231JVH (Calcitriol) RN - Q0OZ0D9223 (seocalcitol) SB - IM MH - Animals MH - Antineoplastic Agents/*pharmacology MH - Apoptosis/drug effects MH - Blotting, Northern MH - Calcitriol/*analogs & derivatives/pharmacology MH - Gene Expression MH - Insulin-Like Growth Factor Binding Protein 2/genetics MH - Insulin-Like Growth Factor Binding Protein 3/genetics MH - Insulin-Like Growth Factor Binding Protein 4/genetics MH - Insulin-Like Growth Factor Binding Protein 5/genetics MH - Insulin-Like Growth Factor Binding Proteins/*genetics MH - Insulin-Like Growth Factor I/genetics MH - Male MH - Prostate/*drug effects/metabolism/physiology MH - RNA, Messenger/analysis MH - Rats MH - Rats, Sprague-Dawley EDAT- 1999/01/30 00:00 MHDA- 1999/01/30 00:01 CRDT- 1999/01/30 00:00 PHST- 1999/01/30 00:00 [pubmed] PHST- 1999/01/30 00:01 [medline] PHST- 1999/01/30 00:00 [entrez] AID - 10.1677/joe.0.1600223 [doi] PST - ppublish SO - J Endocrinol. 1999 Feb;160(2):223-9. doi: 10.1677/joe.0.1600223.