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 f ish. All evidence to date has indicated that the estrogenic effects of NP a re 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 th is species, possibly via induction of aromatase enzymes. In the present stu dies, this hypothesis was investigated in rats using the aromatase inhibito r anastrozole. The results indicated that the uterotrophic action of NP, as with estradiol used as a positive control, is mediated directly by its int eraction with uterine ER, rather than an indirect effect via aromatase enzy me induction. Circulating levels of estradiol were unchanged after NP treat ment and the aromatase inhibitor anastrozole failed to inhibit NP-induced u terine growth. These results are consistent with previous published data on NP in rodents. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.