Transcription of Key Genes Regulating Gonadal Steroidogenesis in Control and Ketoconazole- or Vinclozolin-Exposed Fathead Minnows

• Published in: Toxicological sciences 2007-08, Vol.98 (2), p.395-407
• Main Authors: Villeneuve, Daniel L., Blake, Lindsey S., Brodin, Jeffrey D., Greene, Katie J., Knoebl, Iris, Miracle, Ann L., Martinovic, Dalma, Ankley, Gerald T.
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; ABUNDANCE; Animals; antiandrogen; ANTIANDROGENS; Antifungal Agents - toxicity; BASIC BIOLOGICAL SCIENCES; Cyprinidae; Cytochromes - genetics; Cytochromes - metabolism; Endocrine Disruptors - toxicity; ENZYME ACTIVITY; FATHEAD MINNOW; Female; FEMALES; Follicle Stimulating Hormone, beta Subunit - metabolism; Freshwater; Fungicides, Industrial - toxicity; Gene Expression Regulation - drug effects; GENES; gonad development; GONADS; HORMONES; Hydroxysteroid Dehydrogenases - genetics; Hydroxysteroid Dehydrogenases - metabolism; Ketoconazole - toxicity; LUTEINIZING HORMONE; Luteinizing Hormone, beta Subunit - metabolism; Male; MALES; Ovary - drug effects; Ovary - metabolism; Oxazoles - toxicity; Phosphoproteins - genetics; Phosphoproteins - metabolism; Pimephales promelas; Pituitary Gland - drug effects; Pituitary Gland - metabolism; real-time PCR; Receptors, FSH - genetics; Receptors, FSH - metabolism; Receptors, LH - genetics; Receptors, LH - metabolism; reproduction; RNA, Messenger - metabolism; steroidogenesis inhibitor; Teleostei; testis; Testis - drug effects; Testis - metabolism; TRANSCRIPTION
• ISSN: 1096-6080; 1096-0929
• DOI: 10.1093/toxsci/kfm124

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 β-subunit as well as testis expression of 20β-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.