Hepatic protein expression networks associated with masculinization in the female fathead minnow (Pimephales promelas).
Endocrine disruptors that act via the androgen receptor (AR) are less well studied than environmental estrogens, and there is evidence that treatment with AR agonists can result in masculinization of female fish. In this study, female fathead minnows (FHM) were exposed to the model nonaromatizable androgen 5-alpha dihydrotestosterone (DHT) (100 μg/L), the ureic-based herbicide linuron (LIN) (100 μg/L), and a mixture of DHT and LIN (100 μg/L each) to better characterize androgen action in females. LIN was used because of reports that this chemical has an antiandrogenic mode of action in fish. After 21d, DHT and LIN treatments resulted in a significant depression of plasma vitellogenin (Vtg) and DHT and DHT+LIN increased the prevalence of nuptial tubercles in female FHMs indicating masculinization. Using iTRAQ and an LTQ Orbitrap Velos, ∼2000 proteins were identified in the FHM liver and the number of proteins quantified after exposures was >1200. Proteins that significantly and consistently changed in abundance across biological replicates included prostaglandin E synthase 3, programmed cell death 4a, glutathione S transferases, canopy, selenoprotein U, and ribosomal proteins. Subnetwork enrichment analysis identified that interferon and epidermal growth factor signaling were regulated by DHT and LIN, suggesting that these signaling pathways are correlated to depressed plasma vitellogenin. These data provide novel insight into hepatic protein networks that are associated with the process of masculinization in teleosts.
Canadian Rivers Institute and Department of Biology, University of New Brunswick, Saint John, New Brunswick E2L 4L5, Canada. cmartyn@unb.ca
Christopher J
CJ
Martyniuk
Sophie
S
Alvarez
Bonnie P
BP
Lo
James R
JR
Elphick
Vicki L
VL
Marlatt
D000728:Androgens / Q000633:toxicity; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D016000:Cluster Analysis; D003530:Cyprinidae / Q000378:metabolism* / Q000502:physiology; D013196:Dihydrotestosterone / Q000633:toxicity; D052244:Endocrine Disruptors / Q000633:toxicity; D005260:Female; D029941:Fish Proteins / Q000235:genetics / Q000378:metabolism*; D053263:Gene Regulatory Networks; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006540:Herbicides / Q000633:toxicity; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism; D008044:Linuron / Q000633:toxicity; D008099:Liver / Q000378:metabolism*; D058977:Molecular Sequence Annotation; D000071876:Prostaglandin-E Synthases; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D051140:Selenoproteins / Q000235:genetics / Q000378:metabolism; D012733:Sex Differentiation / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic; D059467:Transcriptome; D014819:Vitellogenins / Q000097:blood
D000728:Androgens; D051017:Apoptosis Regulatory Proteins; D052244:Endocrine Disruptors; D029941:Fish Proteins; D006540:Herbicides; D020543:Proteome; D012269:Ribosomal Proteins; D051140:Selenoproteins; D014819:Vitellogenins; D008044:Linuron; D013196:Dihydrotestosterone; D005982:Glutathione Transferase; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases