The secretion of prostate-specific antigen (PSA) by prostate cancer provides an important tool in the diagnosis and management of this disorder. While androgens are required for PSA synthesis, the neuroendocrine regulation of PSA secretion is less understood. Human prostate is extensively innervated with vasoactive intestinal peptide (VIP)-containing neurons, while both normal and malignant prostate cells contain VIP receptors. Therefore, we investigated the effects of VIP on PSA secretion by LNCaP prostate cancer cells. We found that 1-4-h VIP treatment produces 60-100% increases in PSA secretion by LNCaP cells. Increases in PSA secretion were seen with as little as 10(-10) M VIP with maximum effects at 10(-7) M. The predominant acute effect of VIP was to increase the secretion of stored PSA without increasing PSA mRNA. VIP's effect on PSA secretion involved the production of intracellular cAMP since all doses of VIP which increased secretion were associated with increased cyclic AMP and since dibutyryl-cyclic AMP treatment increased secretion similarly to VIP. These results suggest that VIP regulates PSA secretion by prostate cancer cells and also suggest a role for VIP to regulate PSA secretion by normal prostate epithelial cells.
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