Oestrogen metabolism in lymphangioleiomyomatosis: catechol-O-methyltransferase pathway is not involved
Benoit Paquettea, Pierre-Karl Fortiera c, Julie Hérouxa c, Paul A Thibodeaua, Richard Wagnera, Jiankang Liub, André Cantinc
a Department of
Radiobiology, Faculty of Medicine, Université de Sherbrooke,
Sherbrooke, Québec, Canada J1H 5N4, b Division of Biochemistry and Molecular Biology,
University of California, Berkeley, California 94720, USA, c Department of Medicine, Centre Universitaire de
Santé de l'Estrie, Sherbrooke, Québec,
Canada J1H 5N4
Correspondence to: Dr A Cantin email: a.cantin{at}courrier.usherb.ca
Received 25 October 1999; Returned to authors 12 January 2000; Revised version received 9 March 2000; Accepted for publication 17 March 2000
BACKGROUND
Lymphangioleiomyomatosis
(LAM) is an uncommon lung disease for which no effective method of
treatment has been found. The predilection of LAM for premenopausal
women has led to the assumption that hormonal factors play an important
role in the pathogenesis of this disease. The aim of this study was to
determine if women with LAM manifest alterations in the
catechol-O-methyltransferase (COMT) pathway
which is essential for preventing the generation of oestrogen derived
reactive oxygen species (ROS).
METHODSBlood samples
were collected from 15 women with LAM and compared with appropriate
controls. The distribution of high and low activity alleles of COMT was
determined with a PCR based RFLP assay. The enzymatic activity of COMT
was measured in each sample and the potential presence of a circulating
inhibitor of COMT was determined. Since an alteration in the COMT
pathway could increase the oxidative stress, the plasma concentration
of malondialdehyde (MDA), a secondary product generated from lipid
peroxidation, has been used as an internal marker.
RESULTSThe
distribution of high and low activity alleles of COMT (named
COMTHH,
COMTLL,
and
COMTHL)
was similar in the two groups with proportions of 40%, 7%, and 53%,
respectively, in the women with LAM and 38%, 6%, and 56% in the
control subjects. The mean (SD) COMT activity was 24.2 (12.3) pmol/min/mg protein in women with LAM and 24.1 (6.3) pmol/min/mg protein in the control group. Incubation of plasma
from women in the two groups with a preparation of commercial COMT
showed that no detectable COMT inhibitor was present. The plasma
concentration of MDA in the women with LAM was also not significantly
different from control subjects.
CONCLUSIONSThis study
shows that there are no significant alterations in the COMT pathway of
women with LAM. It is therefore unlikely that alterations in oestrogen
mediated cell signalling pathways are mediated by oxidants derived from
an excess of catecholoestrogens in LAM.
Keywords: lymphangioleiomyomatosis; oestrogen metabolism; catechol-O-methyltransferase
© 2000 by Thorax
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