The uterotrophic activity of nonylphenol in the rat is not mediated by aromatase enzyme induction.
p-Nonylphenol (NP) is weakly estrogenic to rodents and to some species of fish. All evidence to date has indicated that the estrogenic effects of NP are due to the interaction of NP with the estrogen receptor. Recent findings of increased plasma estradiol in fish exposed to NP have, however, led to the proposal of an alternative mechanism for NP-induced estrogenicity in this species, possibly via induction of aromatase enzymes. In the present studies, this hypothesis was investigated in rats using the aromatase inhibitor anastrozole. The results indicated that the uterotrophic action of NP, as with estradiol used as a positive control, is mediated directly by its interaction with uterine ER, rather than an indirect effect via aromatase enzyme induction. Circulating levels of estradiol were unchanged after NP treatment and the aromatase inhibitor anastrozole failed to inhibit NP-induced uterine growth. These results are consistent with previous published data on NP in rodents.
Odum
J
J
Syngenta Central Toxicology Laboratory, Alderley Park, Macclesfield, SK10 4TJ, Cheshire, UK.
Tinwell
H
H
Van Miller
J
J
Joiner
R
R
Ashby
J
J
D000077384:Anastrozole; D000818:Animals; D001141:Aromatase / Q000096:biosynthesis*; D047072:Aromatase Inhibitors; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D009570:Nitriles / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D010636:Phenols / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000502:physiology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D014599:Uterus / Q000033:anatomy & histology / Q000187:drug effects* / Q000201:enzymology; D005466:Fluorocarbons
D000077384:Anastrozole; D001141:Aromatase; D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D009570:Nitriles; D010636:Phenols; D011960:Receptors, Estrogen; D013764:Tetrahydronaphthalenes; D014230:Triazoles; C088608:ZM 189154; D005466:Fluorocarbons; C025256:nonylphenol