Modulation by β-naphthoflavone of ovarian hormone dependent responses in rat uterus and liver in vivo

Abstract

The potential of an aryl hydrocarbon receptor (AhR) agonist, beta-naphthoflavone (beta-NF), to modulate ovarian hormone responses in the uterus and liver of 50-day-old Sprague-Dawley rats was examined. Treatment with beta-NF at 40 mg/kg of body weight consisted of 3 or 9 intraperitoneal injections in corn oil administered to ovariectomized (OVX) and sham-treated (SH) rats on day 5 through 7 or 1 through 9 after surgery performed on day 42 or 40 of age, respectively. Treatment of SH rats with either dose regimen of beta-NF effected a decrease (approximately 80%) in the uterine peroxidase activity, which was similar to that effected by ovariectomy (> 93%). By contrast, treatment of rats with alpha-naphthoflavone, an AhR antagonist, did not decrease the peroxidase activity. After the 9-dose treatment with beta-NF, decreases (approximately 70%) in hepatic estrogen receptor (ER) levels in both SH and OVX rats exceeded those effected by ovariectomy (30%). However, treatment with beta-NF partially prevented the ovariectomy-effected increase (approximately 1.5-fold) in body weight gain, decrease (approximately 67%) in uterine weight, and increase (3-fold) in uterine ER level. In both SH and OVX rats, treatment with beta-NF increased (1.7-fold) uterine progesterone receptor (PR) levels, which were unaffected by ovariectomy. Thus, the results suggest that the effect to of treatment with beta-NF is both mimicking and counteracting the effects of estrogen. Since beta-NF itself or upon conversion to metabolites by liver microsomes was shown herein not to be a ligand for uterine ER and PR, the aforementioned effects of beta-NF resembled those of certain halogenated polycyclic hydrocarbons, and thus may be mediated via AhR.