Castration rapidly decreases local insulin-like growth factor-1 levels and inhibits its effects in the ventral prostate in mice.
2006 (English)In: The Prostate, ISSN 0270-4137, Vol. 66, no 16, 1687-1697 p.Article in journal (Refereed) Published
BACKGROUND: The mechanisms by which castration induces prostate involution are largely unknown. METHODS: Early responses to castration in mouse ventral prostate (VP) were explored by quantitative microscopy, cDNA array expression, quantitative RT-PCR, and Western blot analysis. As several changes occurred in the insulin-like growth factor (IGF) system this was studied in more detail. Laser micro-dissection was used to localize sites of IGF-1 and IGF-1 receptor (IGF-R1) production. IGF-1 protein levels and IGF-R1 mediated signaling via insulin regulated substrate 1 and 2 (IRS-1 and 2) were examined. IGF-1 was injected into the VP in intact, and castrated mice and effects studied 1 day later. RESULTS: IGF-1 and IGF binding protein 2 (IGFBP-2) mRNA were rapidly reduced whereas IGFBP-3 and IGF-R1 mRNA were increased after castration. IGF-1 was principally produced in the stromal compartment, while IGF-R1 was produced in both epithelial and stromal cells. IGF-1 and IRS-1 protein levels were decreased 1 and 3 days after castration, respectively, while IRS-2 was unchanged. Inactivating phosphorylation of IRS-1 at serine 307 was increased 1 day after castration, and activating phosphorylation at tyrosine 612 was decreased 2 days later. These changes were accompanied by decreased cell proliferation and increased cell death in the glandular and vascular compartment. Local injection of IGF-1 increased vascular density and epithelial cell proliferation in intact mice, but had no effect in castrated animals. CONCLUSION: Decreased IGF-1 levels and action may mediate some of the key features of castration-induced prostate involution.
Place, publisher, year, edition, pages
2006. Vol. 66, no 16, 1687-1697 p.
Animals, Cell Growth Processes/drug effects/physiology, Epithelial Cells/metabolism, Insulin-Like Growth Factor Binding Protein 2/biosynthesis/genetics/metabolism, Insulin-Like Growth Factor Binding Protein 3/biosynthesis/genetics/metabolism, Insulin-Like Growth Factor I/biosynthesis/genetics/*metabolism/pharmacology, Male, Mice, Oligonucleotide Array Sequence Analysis, Orchiectomy, Phosphoproteins/metabolism, Prostate/blood supply/cytology/drug effects/*physiology, RNA; Messenger/biosynthesis/genetics, Stromal Cells/metabolism
IdentifiersURN: urn:nbn:se:umu:diva-15361DOI: 10.1002/pros.20368PubMedID: 16998818OAI: oai:DiVA.org:umu-15361DiVA: diva2:155033