Phospholipase A2 degradation products modulate epithelial and stromal 5alpha-reductase activity of human benign
Heike Weisser1, Tjalf Ziemssen, Michael Krieg
1Institute of Clinical Chemistry, Transfusion and Laboratory Medicine, University Clinic Bergmannsheil, Bochum, Germany. heike.weisser@ruhr-uni-bochum.de
Background:
Recent studies have demonstrated the inhibition of 5alpha-reductase activity in human prostate by phospholipases. Among those phospholipases, phospholipase A2 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 5alpha-reductase activity in human benign prostatic hyperplasia (BPH).
Methods:
In a first set of experiments, cell homogenates were incubated with phospholipase A2 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 5alpha-reductase activity was investigated.
Results:
In epithelium and stroma of human BPH, 5alpha-reductase activity was inhibited in a dose-dependent manner by phospholipase A2. In the presence of albumin, this inhibition was enhanced. In epithelium, LPC at low concentration yielded a dose-dependent stimulation of 5alpha-reductase activity up to 167%. At higher concentrations, epithelial as well as stromal 5alpha-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 5alpha-reductase. In contrast, LPC reduces the affinity of epithelial 5alpha-reductase to testosterone. LPE had no effect on epithelial 5alpha-reductase, whereas stromal 5alpha-reductase was inhibited in a dose-dependent manner up to 46%. Finally, LPS stimulated epithelial and stromal 5alpha-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 5alpha-reductase.
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