Effects of 17beta-estradiol, 4-nonylphenol and PCB 126 on the estrogenic activity and phase 1 and 2 biotransformation enzymes in male sea bass (Dicentrarchus labrax).
The endocrine system of wildlife is exposed to a wide variety of natural and man-made chemicals which may lead to damage to the reproductive system and other adverse effects, including alteration of drug-metabolizing enzymes. In the present study, the effects of in vivo exposure to a natural (17beta-estradiol: E2) or a xenoestrogen (4-nonylphenol: NP) estrogen or an anti-estrogen (3,3',4,4',5-pentachlorobiphenyl: PCB 126) upon vitellogenin (VTG) synthesis and hepatic phase 1 and 2 enzymes have been investigated in adult male sea bass. By means of ELISA analysis with the use of polyclonal antibodies prepared against VTG purified from E2-treated sea bass, we assessed the time course and sensitivity of VTG induction in the plasma of sea bass treated with E2 at 0.1, 0.5, 2.5 and 5.0 mg/kg doses or NP at 5.0 or 50 mg/kg doses, respectively. Sea bass sensitivity to this induction was found to be similar to that of other fish species, but with a delay in maximal response. E2 treatment also caused a selective time- and dose-dependent inhibition of hepatic CYP1A-linked EROD and phase 2 glutathione S-transferase (GST) activities, without affecting the activity of CYP3A-linked 6beta-testosterone hydroxylase, (omega)- and (omega-1)-lauric acid hydroxylases or phase 2 DT-diaphorase. A similar selective inhibition on CYP1A was also observed in fish treated with 50 mg/kg NP. The results regarding CYP1A and CYP3A were also confirmed by Western blot analysis. When the sea bass were treated with either 10 or 100 microg/kg PCB 126, an AhR ligand not yet tested in vivo in fish to assess its anti-estrogenicity, a modest and selective induction of EROD and DT-diaphorase activities was observed. Interestingly, both these activities were recovered to their control levels in sea bass co-treated with 0.5 mg/kg E2 and 10 or 100 microg/kg PCB 126, probably through a cross-talk mechanism between the estrogen receptor and AhR or other transcription factors that regulate the expression of these enzymes. Furthermore, it was demonstrated that PCB 126 possesses a potent anti-estrogenic activity in the sea bass in vivo as it inhibited the E2-induced VTG synthesis with an IC50 of 28 microg/kg. The results of this study suggest that the exposure of fish to xenoestrogens or anti-estrogens may alter, in addition to various physiological processes, the expression of specific CYPs and phase 2 enzymes, thereby reducing the capability of their detoxication system.
Vaccaro
Emilia
E
Istituto di Fisiologia Clinica, via G. Moruzzi 1, Area della Ricerca CNR, 56100 Pisa, Italy.
Meucci
Valentina
V
Intorre
Luigi
L
Soldani
Giulio
G
Di Bello
Domenica
D
Longo
Vincenzo
V
Gervasi
Pier Giovanni
PG
Pretti
Carlo
C
D000818:Animals; D001492:Bass / Q000378:metabolism*; D015153:Blotting, Western; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000633:toxicity*; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D010636:Phenols / Q000633:toxicity*; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D014819:Vitellogenins / Q000096:biosynthesis*; D014874:Water Pollutants, Chemical / Q000633:toxicity*
D010636:Phenols; D014819:Vitellogenins; D014874:Water Pollutants, Chemical; D004958:Estradiol; D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase; C041594:4-nonylphenol; C023035:3,4,5,3',4'-pentachlorobiphenyl