The role of hsp90 in 17alpha-ethynylestradiol-induced endocrine disruption in rainbow trout hepatocytes.
The potent synthetic estrogen, 17alpha-ethynylestradiol (EE2) can affect fish by competing with naturally produced estrogen for ligand binding sites on the estrogen receptor (ER). This activation step ultimately leads to endocrine disruption, often indicated by the increased production of vitellogenin protein (Vg). We reasoned that the binding of EE2 to the ER in fish is dependent upon the stabilization of the receptor by the molecular chaperone, hsp90. To test this hypothesis, we exposed hepatocytes from rainbow trout (Oncorhynchus mykiss) to EE2 and the specific hsp90 inhibitor, radicicol (RAD), to block hsp90 chaperone activity during EE2 treatment. Vg production was significantly reduced in the presence of RAD, implicating hsp90 in the mechanism of endocrine disruption via EE2. To our knowledge, this is the first indication that the stress protein, hsp90 is an important component of ER signaling in fish.
Osborne
Nolan
N
Department of Biology, Mount Allison University, Sackville, New Brunswick, Canada E4L 1G7.
Sherry
James
J
Rendell
Jillian L
JL
Currie
Suzanne
S
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004967:Estrogens / Q000633:toxicity*; D004997:Ethinyl Estradiol / Q000633:toxicity*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D018942:Macrolides / Q000494:pharmacology; D017686:Oncorhynchus mykiss; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D014819:Vitellogenins / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity
D004338:Drug Combinations; D004791:Enzyme Inhibitors; D004967:Estrogens; D018841:HSP90 Heat-Shock Proteins; D018942:Macrolides; D014819:Vitellogenins; D014874:Water Pollutants, Chemical; D004997:Ethinyl Estradiol; D007770:L-Lactate Dehydrogenase; D011505:Protein-Tyrosine Kinases; C035359:monorden