title: Transcription of key genes regulating gonadal steroidogenesis in control and ketoconazole- or vinclozolin-exposed fathead minnows.
abstract: This study evaluated changes in the expression of steroidogenesis-related genes in male fathead minnows exposed to ketoconazole (KTC) or vinclozolin (VZ) for 21 days. The aim was to evaluate links between molecular changes and higher level outcomes after exposure to endocrine-active chemicals (EACs) with different modes of action. To aid our analysis and interpretation of EAC-related effects, we first examined variation in the relative abundance of steroidogenesis-related gene transcripts in the gonads of male and female fathead minnows as a function of age, gonad development, and spawning status, independent of EAC exposure. Gonadal expression of several genes varied with age and/or gonadal somatic index in either males or females. However, with the exception of aromatase, steroidogenesis-related gene expression did not vary with spawning status. Following the baseline experiments, expression of the selected genes in male fathead minnows exposed to KTC or VZ was evaluated in the context of effects observed at higher levels of organization. Exposure to KTC elicited changes in gene transcription that were consistent with an apparent compensatory response to the chemical's anticipated direct inhibition of steroidogenic enzyme activity. Exposure to VZ, an antiandrogen expected to indirectly impact steroidogenesis, increased pituitary expression of follicle-stimulating hormone beta-subunit as well as testis expression of 20beta-hydroxysteroid dehydrogenase and luteinizing hormone receptor transcripts. Results of this study contribute to ongoing research aimed at understanding responses of the teleost hypothalamic-pituitary-gonadal axis to different types of EACs and how changes in molecular endpoints translate into apical outcomes reflective of either adverse effect or compensation.
authors.affiliation: U.S. Environmental Protection Agency, ORD, NHEERL, Mid-Continent Ecology Division, Duluth, Minnesota 55804, USA. villeneuve.dan@epa.gov
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Villeneuve
authors.forename: Lindsey S
authors.initials: LS
authors.lastname: Blake
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Brodin
authors.forename: Katie J
authors.initials: KJ
authors.lastname: Greene
authors.forename: Iris
authors.initials: I
authors.lastname: Knoebl
authors.forename: Ann L
authors.initials: AL
authors.lastname: Miracle
authors.forename: Dalma
authors.initials: D
authors.lastname: Martinovic
authors.forename: Gerald T
authors.initials: GT
authors.lastname: Ankley
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000633:toxicity*; D003530:Cyprinidae; D003580:Cytochromes / Q000235:genetics / Q000378:metabolism; D052244:Endocrine Disruptors / Q000633:toxicity; D005260:Female; D037201:Follicle Stimulating Hormone, beta Subunit / Q000378:metabolism; D005659:Fungicides, Industrial / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism; D007654:Ketoconazole / Q000633:toxicity*; D037101:Luteinizing Hormone, beta Subunit / Q000378:metabolism; D008297:Male; D010053:Ovary / Q000187:drug effects / Q000378:metabolism; D010080:Oxazoles / Q000633:toxicity*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011962:Receptors, FSH / Q000235:genetics / Q000378:metabolism; D011974:Receptors, LH / Q000235:genetics / Q000378:metabolism; D013737:Testis / Q000187:drug effects / Q000378:metabolism; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D000935:Antifungal Agents; D003580:Cytochromes; D052244:Endocrine Disruptors; D037201:Follicle Stimulating Hormone, beta Subunit; D005659:Fungicides, Industrial; D037101:Luteinizing Hormone, beta Subunit; D010080:Oxazoles; D010750:Phosphoproteins; D012333:RNA, Messenger; D011962:Receptors, FSH; D011974:Receptors, LH; D000098682:Steroidogenic Acute Regulatory Protein; D006913:Hydroxysteroid Dehydrogenases; C025643:vinclozolin; D007654:Ketoconazole