Modulation by beta-naphthoflavone of ovarian hormone dependent responses in rat uterus and liver in vivo.
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.
Brauze
D
D
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis 55455, USA.
Crow
J S
JS
Malejka-Giganti
D
D
D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006728:Hormones / Q000502:physiology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D011980:Receptors, Progesterone / Q000187:drug effects / Q000378:metabolism; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism; D019324:beta-Naphthoflavone / Q000494:pharmacology*
D001571:Benzoflavones; D004791:Enzyme Inhibitors; D006728:Hormones; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D004958:Estradiol; C011512:alpha-naphthoflavone; D019324:beta-Naphthoflavone; D009195:Peroxidase; D019363:Cytochrome P-450 CYP1A1