کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
9895191 1542746 2005 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Valproate is an anti-androgen and anti-progestin
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Valproate is an anti-androgen and anti-progestin
چکیده انگلیسی
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-β-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 μM CBZ or VPA or (b) to detect antagonist activity by exposing yeast stimulated with testosterone (5 × 10−9 M, AR), progesterone (1.6 × 10−9 M, PR) or estradiol (2.6 × 10−11 M, ER) together with either VPA or CBZ for 4 (PR) or 16 (AR, ER) hours. VPA showed dose-dependent (1-800 μM) 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 μM) blockade of DHT's suppression of AR-mediated NF-κB 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 μM) 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 μM) seems likely to contribute to the frequency of reproductive endocrine disturbances among patients treated with VPA.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Steroids - Volume 70, Issue 14, 15 December 2005, Pages 946-953
نویسندگان
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