ESTROGEN-RECEPTOR (ER) AND ITS MESSENGER-RIBONUCLEIC-ACID EXPRESSION IN THE GENITAL-TRACT OF FEMALE MICE EXPOSED NEONATALLY TO TAMOXIFEN AND DIETHYLSTILBESTROL

Background: Tamoxifen (Tx) is known as an antiestrogen because of its competitive inhibition of estrogen binding to estrogen receptor (ER), and it is used as an estrogen antagonist in the human breast. However, Tx is known to have estrogen agonist activity in the human fetal repr oductive tracts and vaginal epithelium and endometrium of postmenopaus al women as has been known in the mouse uterus. Therefore, we examined estrogenic potency of Tx on the uterus and vagina in newborn mice and adult ovariectomized mice. Methods: Using immunohistochemistry and in situ hybridization, we studied changes in expression of ER protein an d ER mRNA in the uterus and vagina of C57BL/Tw mice exposed neonatally to 100 mu g Tx and 0.03-3 mu g diethylstilbestrol (DES), and changes in expression of ER mRNA in the ovariectomized adult mice given inject ions of 100 mu g Tx and 3 mu g DES. Results: Nuclei of the epithelial and stromal cells in the vagina and of the stromal cells in the uterus showed strong ER immunostaining on the day of birth (= day 0), wherea s nuclei of the epithelial cells in the uterus exhibited the ER immuno staining by day 5. In uterine epithelial cells, however, ER was induce d by DES, 17 beta-estradiol, testosterone or Tx 24 h after a single in jection on day 0, but not by the injection of 5 alpha-dihydrotestoster one, progesterone, or epidermal growth factor. ER in uterine epithelia l cells was detected even 12 h after a single injection of 3 mu g DES on day 0. ER mRNA expression of uterine and vaginal epithelial cells o f newborn mice increased 4 h after a single injection of 3 mu g DES. E R mRNA expression of uterine and vaginal stromal cells in neonatal mic e increased 4 h after a single injection of 100 mu g Tx. In uterine ep ithelial and stromal cells and vaginal epithelial cells of ovariectomi zed adult mice, ER mRNA expression increased 12 h after a single injec tion of 3 mu g DES and 100 mu g Tx. Conclusions: The present study ind icates that Tx acts as ER inducer in the uterus and vagina of neonatal and ovariectomized adult mice. However, responsiveness of reproductiv e tracts to Tx is different between newborn and adult mice. (C) 1996 W iley-Liss, Inc.