Expression of c-fos and c-jun protooncogenes in the uteri of immature mice neonatally exposed to diethylstilbestrol.
We studied the cell-type-specific and temporal expression of c-fos and c-jun protooncogenes after 17beta-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 immunoreactivity 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.
Yamashita
S
S
Keio Junior College of Nursing, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. shuji@sc.itc.keio.ac.jp
Takayanagi
A
A
Shimizu
N
N
D000818:Animals; D004054:Diethylstilbestrol / Q000494:pharmacology*; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D016762:Genes, fos; D016758:Genes, jun; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D014599:Uterus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*
D004968:Estrogens, Non-Steroidal; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D004054:Diethylstilbestrol