Valproate is an anti-androgen and anti-progestin.

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Show simple item record Death, AK McGrath, KC Handelsman, DJ 2012-02-10T06:08:57Z 2005-12
dc.identifier.citation Steroids, 2005, 70 (14), pp. 946 - 953
dc.identifier.issn 0039-128X
dc.identifier.other C1UNSUBMIT en_US
dc.description.abstract Anti-convulsant treatment is associated with a high prevalence of reproductive dysfunction compared with age-matched non-epileptics. We examined the widely used anti-convulsants valproate (VPA) and carbamazepine (CBZ) for steroidal bioactivity using a yeast-based steroid receptor-beta-galactosidase reporter assay for the androgen receptor (AR), progesterone receptor (PR) or estrogen receptor (ER). Bioassays were performed (a) to detect agonist activity by exposing yeast to 100 microM CBZ or VPA or (b) to detect antagonist activity by exposing yeast stimulated with testosterone (5 x 10(-9) M, AR), progesterone (1.6 x 10(-9) M, PR) or estradiol (2.6 x 10(-11) M, ER) together with either VPA or CBZ for 4 (PR) or 16 (AR, ER) hours. VPA showed dose-dependent (1-800 microM) inhibition of progesterone-induced PR- and testosterone-induced AR activity but had no ER antagonist bioactivity and no significant PR, AR or ER agonist bioactivity. VPA also showed a dose-dependent (1-200 microM) blockade of DHT's suppression of AR-mediated NF-kappaB activation in human mammalian cells. By contrast, CBZ had no significant PR, AR or ER agonist or AR and ER antagonist bioactivity but at the highest concentration tested (800 microM) it did antagonize PR activity. We conclude that VPA is a non-steroidal antagonist for human AR and PR but not ER. VPA's androgen and progesterone antagonism at concentrations within therapeutic blood levels (350-700 microM) seems likely to contribute to the frequency of reproductive endocrine disturbances among patients treated with VPA.
dc.format Print-Electronic
dc.language eng
dc.relation.hasversion Accepted manuscript version en_US
dc.relation.isbasedon 10.1016/j.steroids.2005.07.003
dc.title Valproate is an anti-androgen and anti-progestin.
dc.type Journal Article
dc.parent Steroids
dc.journal.volume 14
dc.journal.volume 70
dc.journal.number 14 en_US
dc.publocation New York en_US
dc.identifier.startpage 946 en_US
dc.identifier.endpage 953 en_US SCI.Medical and Molecular Biosciences en_US
dc.conference Verified OK en_US
dc.for 1103 Clinical Sciences
dc.personcode 108123
dc.personcode 111077
dc.percentage 100 en_US Clinical Sciences en_US
dc.classification.type FOR-08 en_US
dc.edition en_US
dc.custom en_US en_US
dc.location.activity ISI:000234549400004 en_US
dc.description.keywords Humans
dc.description.keywords Carbamazepine
dc.description.keywords Estradiol
dc.description.keywords Progesterone
dc.description.keywords Testosterone
dc.description.keywords Androgen Antagonists
dc.description.keywords Gonadal Steroid Hormones
dc.description.keywords NF-kappa B
dc.description.keywords Receptors, Progesterone
dc.description.keywords Biological Assay
dc.description.keywords Dose-Response Relationship, Drug
dc.description.keywords Valproic Acid
dc.description.keywords Yeasts
dc.description.keywords Progestins
dc.description.keywords Androgen Receptor Antagonists
pubs.embargo.period Not known
pubs.organisational-group /University of Technology Sydney
pubs.organisational-group /University of Technology Sydney/Faculty of Science
pubs.organisational-group /University of Technology Sydney/Faculty of Science/School of Medical and Molecular Sciences
pubs.organisational-group /University of Technology Sydney/Strength - Health Technologies
utslib.copyright.status Open Access 2015-04-15 12:23:47.074767+10
pubs.consider-herdc false
utslib.collection.history General (ID: 2)

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