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 probabl
y subserve a paracrine or local regulatory role in both prostatic grow
th and differentiation as well as the exocrine secretory process. Neur
oendocrine cells may be involved in the etiology of benign prostatic h
yperplasia (BPH). In this study the number of NE cells in areas of BPH
was compared with normal tissue using 5-HT immunocytochemistry. In ad
dition, using high-performance liquid chromatography with electrochemi
cal detection (HPLC-ECD), tissue levels of 5-HT and its metabolite 5-h
ydroxy-indoleacetic acid (5-HIAA) were analyzed in prostatic tissue ex
tracts including 25 cases of BPH and 16 cases of normal tissue verifie
d by adjacent histologic sections. Compared with normal prostate our r
esults demonstrated a marked decrease in 5-HT immunoreactive NE cells
in the vast majority of larger hyperplastic nodules of BPH. These find
ings were corroborated by quantitative analysis where a significant re
duction 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 nodu
les of BPH were studied, abundant NE cells, equal or increased in numb
er compared with those in adjacent normal prostatic tissue, were seen.
The small apparently developing BPH nodules and ductal-like structure
s contained NE cells which may be growth foci near the periphery of so
me hyperplastic nodules. These findings particularly in small hyperpla
stic nodules suggest that NE cells and their products are involved in
controlling cell proliferation through a paracrine hormonal mechanism
and may be involved in the pathogenesis of BPH. Serotonin (5-HT) and N
E peptides may represent that elusive local ''missing link'' often all
uded to in various theories relating to the development of early nodul
ar hyperplasia in BPH.