Exposure to diethylstilbestrol during a critical developmental period of the mouse reproductive tract leads to persistent induction of two estrogen-regulated genes.
Exposure to estrogens during critical periods of development induces teratogenic and carcinogenic lesions in the reproductive tracts of humans and experimental animals. It is important to determine the molecular and cellular targets of estrogenic chemicals and to establish the mechanisms by which interactions of estrogens with the developing genital tract results in permanent lesions of growth and differentiation. The experiments presented here were designed to examined the effects of neonatal estrogen exposure on the expression of two genes, lactoferrin and epidermal growth factor, that are subject to steroid hormone regulation. Using in situ and Northern RNA hybridization, immunoblotting, and immunohistochemistry, our data demonstrate that exposure to the synthetic estrogen, diethylstilbestrol, during a critical neonatal period results in the persistent ovary-independent induction of mRNA and protein encoded by these two genes in the mouse uterus and vagina. The constitutive expression of lactoferrin and EGF, and probably other estrogen-regulated genes, may contribute to the establishment of a permanently "estrogenized" phenotype which is then instrumental in the development of abnormal tissue morphogenesis, function, and neoplasia in the rodent reproductive tract.
Nelson
K G
KG
National Institute of Environmental Health Sciences, Laboratory of Developmental and Reproductive Toxicology, Research Triangle Park, North Carolina 27709.
Sakai
Y
Y
Eitzman
B
B
Steed
T
T
McLachlan
J
J
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D004054:Diethylstilbestrol / Q000633:toxicity*; D004815:Epidermal Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007781:Lactoferrin / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000096:biosynthesis; D014599:Uterus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D014621:Vagina / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*
D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D004054:Diethylstilbestrol; D007781:Lactoferrin