Acetaminophen elicits anti-estrogenic but not estrogenic responses in the immature mouse

Acetaminophen is a widely used analgesic, which has exhibited evidence of e strogenic activity in estrogen-receptor positive human breast cancer cells. However. there is limited in vivo experimentation regarding the estrogenic ity of acetaminophen. Therefore, the present study examined the in vivo est rogenic potential of acetaminophen using the immature Female mouse model. S pecifically, C57B1/6 female mice were treated with acetaminophen (100, 200 and 750 mg/kg per day, i.p.) for 3 consecutive days. Positive controls rece ived estradiol (10 mug/kg per day, i.p.) for 3 consecutive days. Markers of estrogenic activity examined were uterine weight, uterine peroxidase activ ity and progesterone receptor (PR) up-regulation. The results demonstrated that, at all three doses, acetaminophen did not significantly increase uter ine weight, uterine peroxidase activity or PR levels. However, the co-admin istration of E-2 and acetaminophen (200 mg/kg per day, 3 days, i.p.) result ed in a decrease in the E-2-induced upregulation of uterine and hepatic nuc lear PR (uterine PR Values of 39.7 +/-6.6 and 23.7 +/-3.4 fmol/mg for E-2 vehicle and E-2 + acetaminophen, respectively, P < 0.05). Additionally, th e estradiol-induced increase in uterine peroxidase was decreased 75%, by ac etaminophen (200 mg/kg per day, 3 days, i.p.). Therefore, in the immature m ouse model acetaminophen treatment did not elicit estrogenic activity. Howe ver, acetaminophen had a limited ability to antagonize the effects of E-2. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.