PMID- 18648085 OWN - NLM STAT- MEDLINE DCOM- 20081223 LR - 20151119 IS - 1096-0929 (Electronic) IS - 1096-0929 (Linking) VI - 106 IP - 1 DP - 2008 Nov TI - Do parabens have the ability to interfere with steroidogenesis? PG - 206-13 LID - 10.1093/toxsci/kfn148 [doi] AB - The effects of ethyl and butyl paraben on steroidogenesis were evaluated in rats exposed in utero. Pregnant Wistar rats were dosed from gestational day (GD) 7 to GD 21, followed by examination of the dams, and the fetuses. Additionally, both parabens were tested in vitro in the H295R steroidogenesis assay and in the T-screen assay, the later to test for their ability to act as thyroid hormone receptor agonist or antagonist. In the in utero exposure toxicity study, neither ethyl nor butyl paraben showed any treatment-related effects on testosterone production, anogenital distance, or testicular histopathology. However, butyl paraben caused a significant decrease in the mRNA expression level of estradiol receptor-beta in fetal ovaries, and also significantly decreased the mRNA expression of steroidogenic acute regulatory protein and peripheral benzodiazepine receptor in the adrenal glands. In vitro butyl paraben increased the proliferation of the GH3 cells in the T-Screen assay, thereby acting as a weak thyroid hormone receptor agonist. In the adrenal H295R steroidogenesis assay both ethyl and butyl paraben caused a significant increase in the progesterone formation. Overall, the results indicate that butyl paraben might have the ability to act as endocrine disruptor by interfering with the transport of cholesterol to the mitochondrion, thereby interfering with steroidogenesis, but also that the two tested parabens do not show clear endocrine disrupting capabilities in our short-term in vivo experiment. FAU - Taxvig, Camilla AU - Taxvig C AD - National Food Institute, Technical University of Denmark, Department of Toxicology and Risk Assessment, DK-2860 Soborg, Denmark. camta@food.dtu.dk FAU - Vinggaard, Anne Marie AU - Vinggaard AM FAU - Hass, Ulla AU - Hass U FAU - Axelstad, Marta AU - Axelstad M FAU - Boberg, Julie AU - Boberg J FAU - Hansen, Pernille Reimer AU - Hansen PR FAU - Frederiksen, Hanne AU - Frederiksen H FAU - Nellemann, Christine AU - Nellemann C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080722 PL - United States TA - Toxicol Sci JT - Toxicological sciences : an official journal of the Society of Toxicology JID - 9805461 RN - 0 (Endocrine Disruptors) RN - 0 (Gonadal Steroid Hormones) RN - 0 (Parabens) RN - 0 (Phosphoproteins) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Estradiol) RN - 0 (Receptors, GABA-A) RN - 0 (Receptors, Thyroid Hormone) RN - 0 (steroidogenic acute regulatory protein) RN - 14255EXE39 (ethyl-p-hydroxybenzoate) RN - 3QPI1U3FV8 (butylparaben) RN - 3XMK78S47O (Testosterone) RN - 4G7DS2Q64Y (Progesterone) SB - IM MH - Adrenal Glands/*drug effects/embryology/metabolism MH - Animals MH - Cell Line MH - Cell Proliferation/drug effects MH - Dose-Response Relationship, Drug MH - Endocrine Disruptors/*toxicity MH - Female MH - Gestational Age MH - Gonadal Steroid Hormones/*biosynthesis/blood MH - Male MH - Ovary/*drug effects/embryology/metabolism MH - Parabens/*toxicity MH - Phosphoproteins/genetics/metabolism MH - Pituitary Gland/drug effects/metabolism MH - Pregnancy MH - *Prenatal Exposure Delayed Effects MH - Progesterone/biosynthesis MH - RNA, Messenger/metabolism MH - Rats MH - Rats, Wistar MH - Receptors, Estradiol/genetics/metabolism MH - Receptors, GABA-A/genetics/metabolism MH - Receptors, Thyroid Hormone/agonists/metabolism MH - Testis/*drug effects/embryology/metabolism MH - Testosterone/biosynthesis EDAT- 2008/07/24 09:00 MHDA- 2008/12/24 09:00 CRDT- 2008/07/24 09:00 PHST- 2008/07/24 09:00 [pubmed] PHST- 2008/12/24 09:00 [medline] PHST- 2008/07/24 09:00 [entrez] AID - kfn148 [pii] AID - 10.1093/toxsci/kfn148 [doi] PST - ppublish SO - Toxicol Sci. 2008 Nov;106(1):206-13. doi: 10.1093/toxsci/kfn148. Epub 2008 Jul 22.