Vasoactive intestinal peptide (VIP) stimulates rat prostatic epithelial cell proliferation

BACKGROUND. Androgens play a major role in supporting normal growth and fun ctional. maintenance in the prostate. However, this gland contains an array of neuroendocrine peptides that can play a regulatory role in its physiopa thology. Among these peptides, one of the best studied is vasoactive intest inal peptide (VIP), which is abundant in autonomic nerves surrounding both human and rat prostatic acini. This neuropeptide may act through interactio n with two types of high-affinity receptors, named VPAC(1) and VPAC(2) rece ptors. Another regulatory peptide, the pituitary adenylate cyclase-activati ng peptide (PACAP), interacts with these receptors with the same affinity a s VIP, but binds with higher affinity to PAC(1) receptors. Human prostate t umors and rat prostate show a major presence of VPAC(1) receptors, whereas various findings suggest a role for VIP in prostatic development. Here we s tudied the effects of VIP on the proliferation of rat prostatic epithelial cells in culture. METHODS. We studied the [H-3]-thymidine uptake by rat prostatic epithelial cells in culture, characterized previously by using biomarkers such as cyto keratin and vimentin. Ln these cells we tested the effect of VIP and PACAP- 27 on two different signaling pathways, the cyclic AMP (cAMP) and the inosi tol phosphate (IPs). RESULTS. The rat prostatic cells in culture were cytokeratin (5,6,8) and vi mentin positive, indicating that the culture was predominantly epithelial. The proliferation curves showed that the cells followed different states of growth: a quiescent, an exponential proliferative, and a steady state. Cyc lic AMP production, but not inositol phosphate production, was increased in the presence of VIP and PACAP-27, which suggests the expression of VPAC(1) and/or VPAC2 receptors primarily. VIP significantly increased prostatic ce ll proliferation in a bimodal manner, as shown for dibutyryl cyclic AMP (db cAMP), which suggests that the effect of VIP upon prostatic proliferation i s cAMP-dependent. CONCLUSIONS. Here, we demonstrate that VIP increased [H-3]thymidine uptake by rat prostatic epithelial cells in culture, conceivably by the activation of the adenylate cyclase. (C) 2001 Wiley-Liss, Inc.