Inhibition of apoptosis in ventral prostate after castration by androgens is associated with alteration of IGF system of mitogens

Insulin-like growth factor (IGF) I protects cells from apoptosis and plays an essential role in normal prostate physiology, We have previously shown t hat apoptosis is induced in the rat ventral prostate within 6 hours after c astration and is temporally associated with increased expression of the gen es for IGF-binding proteins (IGFBPs) 2, 3, 4, and 5, Because IGFBPs modulat e IGF action and are potential mediators of apoptosis and involution of the prostate gland, we studied the effects of androgen replacement on apoptosi s and the expression of ICF-I and IGFBPs in the ventral prostate after cast ration, Short-term administration of 5 alpha-dihydrotestosterone (DHT) by d aily injections (3 mu g/kg of body weight) slightly delayed, but was not ab le to overcome, castration-induced IGFBP gene expression and apoptosis in t he ventral prostate, Induction of expression of TRPM-2, a gene known to be associated with involution in the prostate after castration, was also sligh tly delayed by injections of DHT and was observed to lag behind expression of IGFBPs and induction of apoptosis, In contrast, constant release of eith er testosterone or DHT from implants for 2 weeks effectively prevented cast ration-induced IGFBP gene expression and apoptosis, Our data suggest that p rostatic testosterone or DHT must stay above a critical concentration in or der to inhibit IGFBP gene expression and to maintain healthy prostate cells .