Relationship of neuroendocrine cells of prostate and serotonin to benign prostatic hyperplasia.

Neuroendocrine (NE) cells containing neurosecretory granules, rich in various peptide hormones and biogenic amines such as serotonin (5-HT), are components of the human prostate epithelium. The NE cells probably subserve a paracrine or local regulatory role in both prostatic growth and differentiation as well as the exocrine secretory process. Neuroendocrine cells may be involved in the etiology of benign prostatic hyperplasia (BPH). In this study the number of NE cells in areas of BPH was compared with normal tissue using 5-HT immunocytochemistry. In addition, using high-performance liquid chromatography with electrochemical detection (HPLC-ECD), tissue levels of 5-HT and its metabolite 5-hydroxy-indoleacetic acid (5-HIAA) were analyzed in prostatic tissue extracts including 25 cases of BPH and 16 cases of normal tissue verified by adjacent histologic sections. Compared with normal prostate our results demonstrated a marked decrease in 5-HT immunoreactive NE cells in the vast majority of larger hyperplastic nodules of BPH. These findings were corroborated by quantitative analysis where a significant reduction in the tissue 5-HT levels in BPH (0.539 +/- 0.09 SE) compared with normal (1.75 +/- 0.22 SE) (p < 0.05) was found. When smaller nodules of BPH were studied, abundant NE cells, equal or increased in number compared with those in adjacent normal prostatic tissue, were seen. The small apparently developing BPH nodules and ductal-like structures contained NE cells which may be growth foci near the periphery of some hyperplastic nodules. These findings particularly in small hyperplastic nodules suggest that NE cells and their products involved in controlling cell proliferation through a paracrine hormonal mechanism and may be involved in the pathogenesis of BPH. Serotonin (5-HT) and NE peptides may represent that elusive local "missing link" often alluded to in various theories relating to the development of early nodular hyperplasia in BPH.