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 reproductive tracts and vaginal epithelium and endometrium of postmenopausal 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 and ER mRNA in the uterus and vagina of C57BL/Tw mice exposed neonatally to 100 micrograms Tx and 0.03-3 micrograms diethylstilbestrol (DES), and changes in expression of ER mRNA in the ovariectomized adult mice given injections of 100 micrograms Tx and 3 micrograms 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), whereas nuclei of the epithelial cells in the uterus exhibited the ER immunostaining by day 5. In uterine epithelial cells, however, ER was induced by DES, 17 beta-estradiol, testosterone or Tx 24 h after a single injection on day 0, but not by the injection of 5 alpha-dihydrotestosterone, progesterone, or epidermal growth factor. ER in uterine epithelial cells was detected even 12 h after a single injection of 3 micrograms DES on day 0. ER mRNA expression of uterine and vaginal epithelial cells of newborn mice increased 4 h after a single injection of 3 micrograms DES. ER mRNA expression of uterine and vaginal stromal cells in neonatal mice increased 4 h after a single injection of 100 micrograms Tx. In uterine epithelial and stromal cells and vaginal epithelial cells of ovariectomized adult mice, ER mRNA expression increased 12 h after a single injection of 3 micrograms DES and 100 micrograms Tx.


CONCLUSIONS
The present study indicates that Tx acts as ER inducer in the uterus and vagina of neonatal and ovariectomized adult mice. However, responsiveness of reproductive tracts to Tx is different between newborn and adult mice.
Sato
T
T
Graduate School of Integrated Science, Yokohama City University, Japan.
Ohta
Y
Y
Okamura
H
H
Hayashi
S
S
Iguchi
T
T
D000818:Animals; D000831:Animals, Newborn; D004054:Diethylstilbestrol / Q000008:administration & dosage / Q000494:pharmacology*; D004338:Drug Combinations; D004965:Estrogen Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005836:Genitalia, Female / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010052:Ovariectomy; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000378:metabolism; D013629:Tamoxifen / Q000008:administration & dosage / Q000494:pharmacology*
D004338:Drug Combinations; D004965:Estrogen Antagonists; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D013629:Tamoxifen; D004054:Diethylstilbestrol