Estrogen-independent expression of neuropsin, a serine protease in the vagina of mice exposed neonatally to diethylstilbestrol.
Perinatal treatment of female mice with natural or synthetic estrogens including diethylstilbestrol (DES) results in estrogen-independent persistent proliferation and cornification of the vaginal epithelium. However, the molecular mechanisms of the estrogen-independent changes have not been elucidated. To analyze the mechanism of estrogen-independent cell proliferation and cornification of the vaginal epithelium, we used differential display and determined specific genes expressed in neonatally DES-treated vagina. A candidate clone that designated DDV5 was identical to the serine protease, neuropsin that is reportedly expressed in the mouse central nervous system. We then analyzed the expression pattern of DDV5/neuropsin using Northern blot analysis. We found: (1). DDV5/neuropsin mRNA is expressed in vaginae from neonatally DES-treated ovariectomized mice but not in vaginae from ovariectomized control mice, (2). its expression is not detected in uteri from neonatally DES-treated mice, (3). DDV5/neuropsin is expressed in vaginae from normal intact mice during estrus. Furthermore, we found that DDV5/neuropsin mRNA rapidly decreased in vaginae after ovariectomy. DDV5/neuropsin was detected in vaginae from ovariectomized mice 48 h after estrogen treatment. These results suggest that DDV5/neuropsin is expressed in estrogen-stimulated mouse vagina, and its gene expression is regulated by estrogen. Neonatal DES exposure affects transcriptional control of DDV5/neuropsin in the mouse vagina, which results in persistent expression of DDV5/neuropsin even after ovariectomy, thus, DDV5/neuropsin may play a role in estrogen-independent persistent proliferation and cornification of the vaginal epithelium. Using in situ hybridization method, we found DDV5/neuropsin mRNA localized in epithelial cells but not stromal cells in vaginae. This is the first report on the gene expression of a serine-protease neuropsin in the mouse vagina, and as a marker of the estrogen-independent persistent proliferation and cornification of the vaginal epithelium.
D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D018076:DNA, Complementary / Q000302:isolation & purification; D004054:Diethylstilbestrol / Q000494:pharmacology*; D004848:Epithelium / Q000187:drug effects; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D007610:Kallikreins / Q000032:analysis / Q000096:biosynthesis*; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger; D012697:Serine Endopeptidases / Q000032:analysis / Q000096:biosynthesis; D014621:Vagina / Q000166:cytology / Q000201:enzymology*
D018076:DNA, Complementary; D004967:Estrogens; D012333:RNA, Messenger; D004054:Diethylstilbestrol; C094799:KLK8 protein, human; D007610:Kallikreins; D012697:Serine Endopeptidases