Insulin affects tissue organization and the kinetics of epithelial cell death in the rat ventral prostate after castration.

Prostate growth and physiology are regulated by steroid hormones and modulated by multiple endocrine factors. We investigated the action of insulin on the tissue organization and kinetics of epithelial cells in the rat ventral prostate (VP) in response to castration up to 120 hours after surgery by using an acute protocol of alloxan-induced diabetes. Diabetes caused a reduction in volume density (V(v%)) and volume of the epithelium. The effects of castration on the epithelium were accelerated in the diabetic animals, as determined by changes in V(v%) and volume. The smooth muscle cells became atrophic and apparently relaxed in response to castration, in contrast to the spinous aspect observed in nondiabetic castrated rats. Counting of apoptotic nuclei in the epithelium showed the classical apoptosis peak at 72 hours in nondiabetic rats and an advance of the apoptosis peak to 48 hours after castration in diabetic rats. Insulin restored the time of the peak to 72 hours. These results were confirmed after immunostaining for cleaved caspase-3 and suggest a survival and antiapoptotic effect on VP epithelial cells in both the presence and absence of androgen stimulation. This idea is supported by the observation that insulin also reduced the overall rate of apoptosis at all experimental points analyzed before and after castration.