title: Fadrozole and finasteride exposures modulate sex steroid- and thyroid hormone-related gene expression in Silurana (Xenopus) tropicalis early larval development.
abstract: Steroidogenic enzymes and their steroid products play critical roles during gonadal differentiation in amphibians; however their roles during embryogenesis remain unclear. The objective of this study was to investigate the expression and activity of aromatase (cyp19; estrogen synthase) and 5 beta-reductase (srd5 beta; 5 beta-dihydrotestosterone synthase) during amphibian embryogenesis. Expression and activity profiles of cyp19 and srd5 beta were first established during Silurana (Xenopus) tropicalis embryogenesis from Nieuwkoop-Faber (NF) stage 2 (2-cell stage; 1h post-fertilization) to NF stage 46 (beginning of feeding; 72 h post-fertilization). Exposures to fadrozole (an aromatase inhibitor; 0.5, 1.0 and 2.0 microM) and finasteride (a putative 5-reductase inhibitor; 25, 50 and 100 microM) were designed to assess the consequences of inhibiting these enzymes on gene expression in early amphibian larval development. Exposed embryos showed changes in both enzyme activities and sex steroid- and thyroid hormone-related gene expression. Fadrozole treatment inhibited cyp19 activity and increased androgen receptor and thyroid hormone receptor (alpha and beta) mRNAs. Finasteride treatment inhibited srd5 beta (activity and mRNA), decreased cyp19 mRNA and activity levels and increased estrogen receptor alpha mRNA. Both treatments altered the expression of deiodinases (thyroid hormone metabolizing enzymes). We conclude that cyp19 and srd5 beta are active in early embryogenesis and larval development in Silurana tropicalis and their inhibition affected transcription of genes associated with the thyroid and reproductive axes.
authors.affiliation: Centre for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Valérie S
authors.initials: VS
authors.lastname: Langlois
authors.forename: Paula
authors.initials: P
authors.lastname: Duarte-Guterman
authors.forename: Sally
authors.initials: S
authors.lastname: Ing
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Pauli
authors.forename: Gerard M
authors.initials: GM
authors.lastname: Cooke
authors.forename: Vance L
authors.initials: VL
authors.lastname: Trudeau
mesh_terms: D000818:Animals; D001141:Aromatase / Q000502:physiology; D047072:Aromatase Inhibitors / Q000008:administration & dosage*; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D047628:Estrogen Receptor alpha / Q000235:genetics; D017316:Fadrozole / Q000008:administration & dosage; D005260:Female; D018120:Finasteride / Q000008:administration & dosage; D015870:Gene Expression / Q000187:drug effects; D012739:Gonadal Steroid Hormones / Q000235:genetics*; D007453:Iodide Peroxidase / Q000235:genetics; D007814:Larva / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D008297:Male; D010088:Oxidoreductases / Q000037:antagonists & inhibitors* / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D011944:Receptors, Androgen / Q000235:genetics; D012098:Reproduction / Q000187:drug effects / Q000235:genetics; D013963:Thyroid Hormones / Q000235:genetics*; D014981:Xenopus / Q000254:growth & development* / Q000378:metabolism
chemical_list: D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D047628:Estrogen Receptor alpha; D012739:Gonadal Steroid Hormones; D012333:RNA, Messenger; D011944:Receptors, Androgen; D013963:Thyroid Hormones; D018120:Finasteride; D010088:Oxidoreductases; D007453:Iodide Peroxidase; D001141:Aromatase; C021936:3-oxo-5 beta-steroid delta 4-dehydrogenase; D017316:Fadrozole