Expression of c-fos and c-jun protooncogenes in the uteri of immature mice neonatally exposed to diethylstilbestrol

S. Yamashita1, A. Takayanagi2 and N. Shimizu2

1Keio Junior College of Nursing and 2Department of Molecular Biology, Keio University, School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo, Japan

Offprint requests to: Shuji Yamashita, Keio Junior College of Nursing, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Fax: 81-3-5363-3730. e-mail: shuji@sc.itc.keio.ac.jp

 

Summary. We studied the cell-type-specific and temporal expression of c-fos and c-jun protooncogenes after 17ß-estradiol (E2) stimulation in the uteri of immature 3-week-old mice neonatally exposed to diethylstilbestrol (DES), DES-mice, and the ontogenic expression of these genes in the uteri of DES-mice using immunohistochemistry and in situ hybridization. A single E2 injection induced the transient and rapid expression of c-fos mRNA and c-Fos protein in the endometrial epithelium and endothelial cells of the blood vessels in both 3-week-old vehicle-treated controls and DES-mice; a peak of mRNA expression was 2 hours after E2 injection and that of protein expression was 2 to 3 hours after the injection. The expression of c-fos mRNA and protein after E2 stimulation was lower in the DES-mice than in the control animals. There were no significant differences in the c-jun expression patterns in both experimental groups before and after the E2 injection. The E2 injection transiently down-regulated the c-jun expression in the epithelium and up-regulated it in the stroma and myometrium. The uterine epithelium of DES-mice showed much stronger c-Jun immunostaining on days 4 and 10, compared with those of controls. Neonatal DES treatment reduced c-Jun immuoreactivity in the uterine epithelium on days 4 and 10, and increased the reaction in the stroma on day 4. These results suggested that the neonatal DES treatment induces permanent changes in the c-fos expression pattern independent of the postpuberal secretion of ovarian steroids. The changes in the expression of c-fos and c-jun protooncogenes, particularly during postnatal development, are likely to play important roles in the production of uterine abnormalities in the DES-mice. Histol. Histopathol. 18, 83-92 (2003)

Key words: c-Fos, c-Jun, Diethylstilbestrol, Uterus, Immature mouse, Immunohistochemistry

DOI: 10.14670/HH-18.83