title: Time-dependent transcriptional profiles of genes of the hypothalamic-pituitary-gonadal axis in medaka (Oryzias latipes) exposed to fadrozole and 17beta-trenbolone.
abstract: Both the anabolic androgen 17beta-trenbolone (TRB) and the aromatase inhibitor fadrozole (FAD) can cause decreased plasma concentrations of estrogen (E2) and reduce fecundity of fish. However, the underlying mechanisms and the molecular pathways involved are largely unknown. The present study was designed to assess time-dependent effects of FAD and TRB on the transcriptional responses of the hypothalamic-pituitary-gonadal (HPG) axis of Japanese medaka (Oryzias latipes). Fourteen-week-old Japanese medaka were exposed to 50 microg FAD/L or 2 microg TRB/L in a 7-d static renewal test, and the expression profiles of 36 HPG axis genes were measured by means of a medaka HPG real-time reverse-transcription polymerase chain reaction array after 8 h, 32 h, or 7 d of exposure. Exposure to TRB or FAD caused lesser fecundity of Japanese medaka and down-regulated transcription of vitellogenin and choriogenin (CHG) gene expression in the liver of females. Exposure to FAD for 8 h resulted in an 8-fold and 71-fold down-regulation of expression of estrogen receptor alpha and choriogenin L (CHG L), respectively, in female liver. 17beta-Trenbolone caused similar down-regulation of these genes, but the effects were not observed until 32 h of exposure. These results support the hypothesis that FAD reduces plasma E2 more quickly by inhibiting aromatase enzyme activity than does TRB, which inhibits the production of the E2 precursor testosterone. Exposure to FAD and TRB resulted in rapid (after 8 h) down-regulation of luteinizing hormone receptor and low-density-lipoprotein receptor in the testis to compensate for excessive androgen levels. Overall, the molecular responses observed in the present study differentiate the mechanisms of the reduced fecundity by TRB and FAD.
authors.affiliation: Department of Zoology, Michigan State University, East Lansing, Michigan 48824, USA. howard50003250@yahoo.com
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zhang
authors.forename: Markus
authors.initials: M
authors.lastname: Hecker
authors.forename: June-Woo
authors.initials: JW
authors.lastname: Park
authors.forename: Amber R
authors.initials: AR
authors.lastname: Tompsett
authors.forename: Paul D
authors.initials: PD
authors.lastname: Jones
authors.forename: John
authors.initials: J
authors.lastname: Newsted
authors.forename: Doris W T
authors.initials: DW
authors.lastname: Au
authors.forename: Richard
authors.initials: R
authors.lastname: Kong
authors.forename: Rudolf S S
authors.initials: RS
authors.lastname: Wu
authors.forename: John P
authors.initials: JP
authors.lastname: Giesy
mesh_terms: D000818:Animals; D047072:Aromatase Inhibitors / Q000633:toxicity*; D017316:Fadrozole / Q000633:toxicity*; D005260:Female; D020869:Gene Expression Profiling; D007030:Hypothalamo-Hypophyseal System; D008297:Male; D009990:Oryzias; D010053:Ovary / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013737:Testis / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*; D014204:Trenbolone Acetate / Q000633:toxicity*
chemical_list: D047072:Aromatase Inhibitors; D017316:Fadrozole; D014204:Trenbolone Acetate