Castration‐induced epithelial cell death in human prostate tissue is related to locally reduced IGF‐1 levels

BACKGROUND: Castration rapidly reduces stroma insulin-like growth factor (IGF)-1 synthesis and action in mouse prostate epithelium. We explore if similar changes are of importance for castration-induced prostate regression in humans. METHODS: Epithelial and surrounding stroma cells were micro-dissected from patient biopsies obtained before and shortly after castration. IGF-1 mRNA levels were quantified by RT-PCR and related to epithelial apoptosis and IGF-1, IGF-1 receptor, and androgen receptor (AR) immunoreactivity. RESULTS: IGF-1 mRNA was principally produced in the stroma and IGF-R1 in the epithelium. Stroma IGF-1 mRNA levels were significantly decreased after castration in non-malignant but not malignant tissue. Lack of stroma IGF-1 reduction after castration was associated with low stroma AR expression before therapy. Reduction of IGF-1 mRNA levels in the tumor stroma and/or epithelium was associated with epithelial apoptosis after therapy. CONCLUSIONS: Low AR expression and maintained stroma IGF-1 synthesis may result in limited tumor cell death after castration therapy.