Dear Ceridwen,
The literature does not appear to have a definite answer to your question as to the mechanism whereby statins can lower serum PSA levels in men.
An in vitro study using immortalised prostate cancer cells published in JCI (Zhuang 2005) concluded that
"Simvastatin significantly decreased the cholesterol content of lipid rafts, inhibited Akt signaling, and stimulated apoptosis in LNCaP cells."
Although there are no published experimental data on a mechanistic explanation for reduction of PSA in men treated with statin, I would like to propose a couple of possible mechanisms:
1. Statins may induce apotosis of normal prostate epithelial cells, which are the main source of PSA, possibly via the Akt signalling pathway. Since PSA is secreted by prostate epithelail cells, a reduction in the number of this cell type will presumably lower PSA levels.
2. By changing the intracellular cholesterol environment, statins may affect the functions of 5alpha-reductase, especially type 2, in prostate cells. This enzyme is believed to be an intrinsic membrane protein embedded in lipid bilayer and its catalytic function was shown to be altered by lipid-modifying compounds. Since PSA gene expression is driven mainly by DHT, a reduction of DHT production by intraprostatic 5alpha-reducatse may potentially reduce PSA secretion.
With best wishes,
Clement
-----
Clement Ho
Specialist Registrar
Clinical Biochemistry
Royal Infirmary of Edinburgh
University of Edinburgh
Little France Crescent
Edinburgh
EH16 4SA
________________________________
Date: Thu, 30 Oct 2008 12:49:19 +0000
From: [log in to unmask]
Subject: Statins and PSA
To: [log in to unmask]
Dear All,
Is anyone able to shed any light on a subject aired in several papers yesterday? Apparently when men are put on statins their PSA levels fall. Dose-related. Not clear what is the cause,direct on release PSA or tissue effect of statin.
I've already had one query from a local GP.
Ceridwen
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