Relative influence of testosterone and insulin in the regulation of prostatic cell proliferation and growth

Abstract

Prostatic hyperplasia is a common problem of the aged men population. Recent experimental and clinical studies provide sufficient evidence that apart from androgens, insulin also plays an important role in the pathogenesis of prostatic hyperplasia. The present study was aimed to investigate the relative influence of testosterone and insulin on the cellular proliferation and prostatic growth. Effect of testosterone on the prostate of hypoinsulinemic, and glandular injection of insulin-receptor antagonist S961 on the prostate of castrated Sprague–Dawley rat (220 ± 10 g) was examined. Significant decrease in the weight of the ventral prostate was observed in the streptozotocin-induced hypoinsulinemic rats (∼6 fold), which is restored by the intervention of testosterone. Although, glandular injection of S961 did not led to any change in the frequency of proliferating cell nuclear antigen (PCNA) positive cells in normal rats, significant decrease was observed in the castrated rats. Castration led to increase in the frequency of the caspase-3 and the TUNEL positive cells in the ventral prostate. Further, long-term (6 weeks) administration of S961 induced significant decrease in the weight of the ventral prostate. Results of the present study provide that both testosterone and insulin promote prostatic cell proliferation and change in the level of either of the hormone results in the destabilization of cellular equilibrium, and modulation of the insulin-receptor signaling in the prostate may provide an alternative strategy for the treatment of prostatic enlargement. Further, studies are required to better understand the interplay between these hormones in the regulation of prostatic growth.