Valproic acid and its derivatives enhanced estrogenic activity but not androgenic activity in a structure dependent manner

Stempin, Sandra; Andres, Susanne; Scheer, Maja Bumke; Rode, Ariane; Nau, Heinz; Seidel, Albrecht; Lampen, Alfonso

doi:10.1016/j.reprotox.2013.07.019

Cited by 9 publications

(6 citation statements)

References 63 publications

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“…Our findings differ slightly in the sense that in WWE with menstrual disorders, VPA was associated with higher estradiol levels, while lamotrigine was associated with lower FSH levels. An in-vitro study demonstrated that VPA directly inhibits ovarian steroid production, namely FSH and estradiol synthesis ( 31 ); however, other studies show that VPA tends to increase estradiol activity, either through inhibition of liver enzymes or enhancement of estrogen receptors ( 32 ). Lower FSH levels have also been discovered in patients who underwent monotherapy with lamotrigine, regardless of their menstrual phase ( 33 ).…”

Section: Discussionmentioning

confidence: 99%

Characteristics of menstrual disorders and reproductive hormones in women with epilepsy at an Indonesian national referral hospital

Octaviana

Sumapraja²,

Wiratman³

et al. 2022

Front. Neurol.

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ObjectiveMenstrual disorders are more common in women with epilepsy than in those without epilepsy. This study aimed to examine the characteristics of reproductive function in women with epilepsy at an Indonesian national referral hospital.MethodsA case-control study was conducted from March 2020 to March 2021. Women with and without epilepsy aged ≥18 years were enrolled. All women were premenopausal before epilepsy diagnosis. Data on demographic characteristics, menstrual profiles, epileptic syndrome, seizure type, seizure frequency, etiology, localization, and anticonvulsant medication were collected. Hormone levels (follicle stimulating hormone, luteinizing hormone, prolactin, and estradiol) were measured.ResultsA total of 72 women with and 50 without epilepsy (controls) were included. Dysmenorrhea was more common in women with epilepsy than in those without (59.7 vs. 20%, p < 0.001; odds ratio: 5.931 [95% confidence interval: 2.566–13.709]). Marriage rates were higher in women without epilepsy (82 vs. 45.8%, p < 0.001). No difference was found in hormone levels between the groups. The frequency of seizures was associated with prolactin and estradiol levels (p < 0.001). Polytherapy with clobazam was associated with menstrual cycle regularity. In women with epilepsy with menstrual disorders, valproic acid was associated with higher estradiol levels (p = 0.001) and lamotrigine with lower follicle stimulating hormone levels (p = 0.008).SignificanceWomen with epilepsy experienced more dysmenorrhea. A higher frequency of seizures associated with lower prolactin and estradiol levels. Polytherapy with clobazam was associated with irregular menstrual cycles, while valproic acid and lamotrigine was associated with estradiol and follicle stimulating hormone levels.

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Section: Discussionmentioning

confidence: 99%

Characteristics of menstrual disorders and reproductive hormones in women with epilepsy at an Indonesian national referral hospital

Octaviana

Sumapraja²,

Wiratman³

et al. 2022

Front. Neurol.

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“…Indeed, this compound can be metabolized into a fatty acid‐CoA complex and then enters the Krebs's cycle for energy production in mitochondria (FCT, ; Federal Register, ). Nevertheless, as recently shown by Stempin et al, () using in vitro experiments, derivatives of short‐chain fatty acids such as 2‐(2‐propynyl)‐nonanoic acid (a derivative of valproic acid with pelargonic acid) could activate the estrogen receptor α (ERα) in stably transfected human cell line (HEK293). Moreover, there may be several ways in which xenobiotics, including nonsteroidogenic chemicals, could interact with the endocrine and reproductive systems of vertebrates, i.e., not only through direct interactions with nuclear receptors but also through modulation of metabolizing enzyme activities, or interferences with hormone binding serum proteins and other nongenomic pathways (Foradori et al, ; De Coster and van Larebeke, ).…”

Section: Discussionmentioning

confidence: 94%

Influence of waterborne gallic and pelargonic acid exposures on biochemical and reproductive parameters in the zebrafish (Danio rerio)

Técher

Milla

Fontaine

et al. 2015

Environmental Toxicology

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Gallic and pelargonic acids are biologically derived substances receiving a growing interest as eco-friendly biocides with potential applications in freshwater system management. However, some data gaps remain to address their chronic ecotoxicity issue, particularly for fish. This work aimed at investigating the sublethal effects of a long-term waterborne exposure of zebrafish to these compounds. Mature fish were exposed to gallic or pelargonic acid at the concentrations of 0, 0.05, 0.5 and 5 mg/L during one month under semi-static conditions. Fecundity, hatching rate and median hatching time were regularly evaluated. Circulating sex hormone levels (11 ketotestosterone -11 KT, 17 βestradiol -E2-), plasma vitellogenin (Vtg), and gonad histology were monitored in males and females after exposure. Lactate dehydrogenase (LDH), total glutathione peroxydase (GPx) and glutathione-S transferase (GST) activities were assessed as enzymatic biomarkers of exposure in fish liver. Significant increases of GPx activity were reported in females exposed to both type of chemicals regardless the contamination level. Moreover, 5 mg/L gallic acid induced a decrease in 11-KT levels for males. For fish exposed to pelargonic acid, decreases in circulating hormone levels were reported respectively at 0.05 and 5 mg/L for 11-KT in males, and at 0.5 mg/L for E2 in females. However, no histological alteration in gonads neither significant variation in reproductive performances were detected following zebrafish exposure to gallic or pelargonic acid. Additional investigations concerning the mode of application and the environmental fate of these substances may warrant their further use in freshwater systems at concentrations compatible with biocidal/allelochemical effects. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 227-240, 2017.

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“…Remarkably, we demonstrated that this approach can be used to identify chemicals that alter endocrine-related functions driving ovary development. estrogenic activity 37 8.9 × 10 −34 steroidogenic effect 38…”

Section: ■ Discussionmentioning

confidence: 99%

In Silico Computational Transcriptomics Reveals Novel Endocrine Disruptors in Largemouth Bass (Micropterus salmoides)

Basili

Zhang

Herbert

et al. 2018

Environ. Sci. Technol.

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In recent years, decreases in fish populations have been attributed, in part, to the effect of environmental chemicals on ovarian development. To understand the underlying molecular events we developed a dynamic model of ovary development linking gene transcription to key physiological end points, such as gonadosomatic index (GSI), plasma levels of estradiol (E2) and vitellogenin (VTG), in largemouth bass ( Micropterus salmoides). We were able to identify specific clusters of genes, which are affected at different stages of ovarian development. A subnetwork was identified that closely linked gene expression and physiological end points and by interrogating the Comparative Toxicogenomic Database (CTD), quercetin and tretinoin (ATRA) were identified as two potential candidates that may perturb this system. Predictions were validated by investigation of reproductive associated transcripts using qPCR in ovary and in the liver of both male and female largemouth bass treated after a single injection of quercetin and tretinoin (10 and 100 μg/kg). Both compounds were found to significantly alter the expression of some of these genes. Our findings support the use of omics and online repositories for identification of novel, yet untested, compounds. This is the first study of a dynamic model that links gene expression patterns across stages of ovarian development.

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Valproic acid and its derivatives enhanced estrogenic activity but not androgenic activity in a structure dependent manner

Cited by 9 publications

References 63 publications

Characteristics of menstrual disorders and reproductive hormones in women with epilepsy at an Indonesian national referral hospital

Characteristics of menstrual disorders and reproductive hormones in women with epilepsy at an Indonesian national referral hospital

Influence of waterborne gallic and pelargonic acid exposures on biochemical and reproductive parameters in the zebrafish (Danio rerio)

In Silico Computational Transcriptomics Reveals Novel Endocrine Disruptors in Largemouth Bass (Micropterus salmoides)

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