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

BACKGROUND. Androgens play a major role in supporting normal growth and functional. maintenance in the prostate. However, this gland contains an array of neuroendocrine peptides that can play a regulatory role in its physiopathology. Among these peptides, one of the best studied is vasoactive intestinal peptide (VIP), which is abundant in autonomic nerves surrounding both human and rat prostatic acini. This neuropeptide may act through interaction with two types of high-affinity receptors, named VPAC(1) and VPAC(2) receptors. Another regulatory peptide, the pituitary adenylate cyclase-activating peptide (PACAP), interacts with these receptors with the same affinity as VIP, but binds with higher affinity to PAC(1) receptors. Human prostate tumors and rat prostate show a major presence of VPAC(1) receptors, whereas various findings suggest a role for VIP in prostatic development. Here we studied 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 cytokeratin 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 inositol phosphate (IPs). RESULTS. The rat prostatic cells in culture were cytokeratin (5,6,8) and vimentin 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. Cyclic 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 cell proliferation in a bimodal manner, as shown for dibutyryl cyclic AMP (dbcAMP), which suggests that the effect of VIP upon prostatic proliferation is 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.