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Phospholipase A 2 degradation products modulate epithelial and stromal 5α‐reductase activity of human benign prostatic hyperplasia in vitro
Author(s) -
Weisser Heike,
Ziemssen Tjalf,
Krieg Michael
Publication year - 2001
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.10027
Subject(s) - reductase , phospholipase a2 , phospholipase , stromal cell , biology , epithelium , endocrinology , biochemistry , medicine , chemistry , enzyme , cancer research , genetics
BACKGROUND Recent studies have demonstrated the inhibition of 5α‐reductase activity in human prostate by phospholipases. Among those phospholipases, phospholipase A 2 cleaves one of the acyl chains from phospholipids, thereby producing fatty acids and lysophospholipids such as LPC, LPS, and LPE. Therefore, we were interested in the effect of those lysophospholipids on 5α‐reductase activity in human benign prostatic hyperplasia (BPH). METHODS In a first set of experiments, cell homogenates were incubated with phospholipase A 2 either in the presence or absence of albumin, which is known to bind fatty acids and lysophospholipids. Thereafter, the effect of lysophospholipids of known structure on 5α‐reductase activity was investigated. RESULTS In epithelium and stroma of human BPH, 5α‐reductase activity was inhibited in a dose‐dependent manner by phospholipase A 2 . In the presence of albumin, this inhibition was enhanced. In epithelium, LPC at low concentration yielded a dose‐dependent stimulation of 5α‐reductase activity up to 167%. At higher concentrations, epithelial as well as stromal 5α‐reductase activity was inhibited significantly. As indicated by results of enzyme kinetic analyses, the LPC‐mediated activation in the epithelium results from an increase of the active population of 5α‐reductase. In contrast, LPC reduces the affinity of epithelial 5α‐reductase to testosterone. LPE had no effect on epithelial 5α‐reductase, whereas stromal 5α‐reductase was inhibited in a dose‐dependent manner up to 46%. Finally, LPS stimulated epithelial and stromal 5α‐reductase activity; this stimulation was significantly stronger in epithelium (296%) than in stroma (163%). The LPC‐mediated effects could be neutralized by the addition of albumin. CONCLUSIONS The present data on BPH tissue suggest that lysophospholipids may play a specific and structure‐related role in the posttranslational regulation of human prostatic 5α‐reductase. Prostate 50: 4–14, 2002. © 2002 Wiley‐Liss, Inc.