Neonatal exposure to diethylstilbestrol permanently alters the basal and 17β-estradiol induced expression of c-fos proto-oncogene in mouse urethroprostatic complex

Perinatal estrogen exposure induces permanent structural and functional changes in the male reproductive tract. We have studied the effect of neonatal estrogenization on the estrogen-responsive c-fos proto-oncogene expression in mouse prostate. Fos is involved in growth and differentiation, and may play a central role in regulating diverse estrogen-related cellular differentiation. In adult control mouse prostate, basal c-fos mRNA expression is very low. Neonatal treatment with diethylstilbestrol on days 1-3 (neoDES) results in permanently increased fos expression in the prostatic urethra and all prostatic lobes. In adult castrated animals, estradiol induces a rapid transient increase in c-fos expression in the prostatic urethra, with maximum induction being higher in neoDES animals. In situ hybridization and immunohistochemistry show that in neoDES mice fos transcripts and protein are localized primarily in the epithelium of posterior periurethral prostatic collecting ducts. These are the sites previously reported to show the most pronounced morphological changes after estrogen treatment. Our results indicate that neonatal estrogenization affects both basal and estrogen stimulated c-fos mRNA levels in the prostate of mature mice, which supports the hypothesis that estrogen-induced morphological changes in mouse prostate may involve altered c-fos expression.