title: The synthetic gestagen levonorgestrel impairs metamorphosis in Xenopus laevis by disruption of the thyroid system.
abstract: Synthetic gestagens, including levonorgestrel (LNG), are active compounds in contraceptives, and several studies report their occurrence in surface waters. However, information about endocrine-disrupting effects in nontarget organisms is scarce. The present study investigated effects of LNG exposure on thyroid hormone-dependent metamorphosis of Xenopus laevis. Premetamorphic X. laevis tadpoles at Nieuwkoop and Faber (NF) stage 48 were exposed in a flow-through culture system to four LNG concentrations (10(-11), 10(-10), 10(-9), and 10(-8)M) over the period of metamorphosis. At NF 58 and 66, tadpoles were examined sex specifically. Developmental time and organismal responses were recorded and correlated with molecular and histopathological endpoints. Exposure to 10(-8)M LNG caused an inhibition of metamorphosis resulting in developmental arrest at early climax stages as giant tadpoles or tailed frogs. In brain-pituitary tissue of NF 58 tadpoles, gene expression of thyroid-stimulating hormone (β-subunit; TSHβ), TH receptor β (TRβ), and deiodinase type 3 (D3) was not changed. Instead, prolactin (PRL) messenger RNA (mRNA) was significantly increased by 10(-9)M LNG in females and by 10(-8)M LNG in both sexes. In NF 66 tadpoles, mRNA levels of TSHβ mRNA were significantly increased in the 10(-9) and 10(-8)M LNG treatment groups indicating a hypothyroid state. No changes of TRβ, D3, and PRL gene expression were detected. Histopathological evaluation of thyroid gland sections revealed no typical sign of hypothyroidism but rather an inactivated appearance of the thyroid. In conclusion, our data demonstrate for the first time a completely new aspect of thyroid system disruption caused by synthetic gestagens in developing amphibians.
authors.affiliation: Department of Ecophysiology and Aquaculture, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, 12587 Berlin, Germany. claudia.lorenz@igb-berlin.de
authors.forename: Claudia
authors.initials: C
authors.lastname: Lorenz
authors.forename: Valeska
authors.initials: V
authors.lastname: Contardo-Jara
authors.forename: Stephan
authors.initials: S
authors.lastname: Pflugmacher
authors.forename: Claudia
authors.initials: C
authors.lastname: Wiegand
authors.forename: Gunnar
authors.initials: G
authors.lastname: Nützmann
authors.forename: Ilka
authors.initials: I
authors.lastname: Lutz
authors.forename: Werner
authors.initials: W
authors.lastname: Kloas
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000254:growth & development; D003271:Contraceptive Agents, Female / Q000633:toxicity*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D048788:Growth and Development / Q000235:genetics; D007814:Larva / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D016912:Levonorgestrel / Q000633:toxicity*; D008136:Longevity / Q000187:drug effects; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects / Q000254:growth & development; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D037322:Thyrotropin, beta Subunit / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014982:Xenopus laevis / Q000502:physiology*
chemical_list: D003271:Contraceptive Agents, Female; D037322:Thyrotropin, beta Subunit; D016912:Levonorgestrel