PMID- 11524234 OWN - NLM STAT- MEDLINE DCOM- 20011004 LR - 20190709 IS - 0022-0795 (Print) IS - 0022-0795 (Linking) VI - 170 IP - 3 DP - 2001 Sep TI - Effect of diethylstilbestrol on cell proliferation and expression of epidermal growth factor in the developing female rat reproductive tract. PG - 539-54 AB - To evaluate mechanisms of cell proliferation in the fetal female rat reproductive tract, diethylstilbestrol (DES) effects on cell division and estrogen receptor (ER), epidermal growth factor (EGF) and EGF receptor (EGF-R) expressions were determined from gestational day (GD) 15.5 to 21.5. Reproductive tracts were evaluated within three regions along the Mullerian duct axis; these were proximal, middle and caudal, which differentiate into oviduct, uterus and upper vagina respectively. In fetuses from non-treated dams, epithelial and mesenchymal proliferation, as evaluated by 5-bromo-2'-deoxyuridine incorporation, was decreased with development in all regions of the Mullerian duct. EGF levels were determined by immunohistochemistry. Mullerian epithelial EGF immunoreactivity was intense in the proximal and middle regions on GDs 15.5 and 17.5. EGF staining remained intense only in the proximal epithelia by GD 19.5 and was weak in the caudal epithelium, but substantially reduced throughout epithelia in all regions by GD 21.5. Thus, decreased cell proliferation correlated with decreased EGF expression in the developing Mullerian duct. DES (100 microg/kg body weight) was injected from GD 15 to 19 and female fetuses were collected on GD 19.5. DES increased Mullerian duct cell proliferation in the proximal epithelium and mesenchyme but decreased it in the caudal epithelium compared with oil-treated controls. No proliferative DES effect was observed in any cell type in the middle region. Mullerian duct EGF immunoreactivity was suppressed by DES compared with oil. Competitive RT-PCR indicated DES also decreased mRNAs for EGF, ERbeta1 and ERbeta2, but not ERalpha and EGF-R. These results indicate EGF may be an important regulatory factor of Mullerian duct cell proliferation, and that DES may alter cell proliferation by disrupting normal EGF, ERbeta1 and ERbeta2 expression in the developing female rat reproductive tract. FAU - Okada, A AU - Okada A AD - Safety Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd, Itabashi, Tokyo 174-8511, Japan. FAU - Sato, T AU - Sato T FAU - Ohta, Y AU - Ohta Y FAU - Buchanan, D L AU - Buchanan DL FAU - Iguchi, T AU - Iguchi T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Endocrinol JT - The Journal of endocrinology JID - 0375363 RN - 0 (Estrogens, Non-Steroidal) RN - 62229-50-9 (Epidermal Growth Factor) RN - 731DCA35BT (Diethylstilbestrol) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - Animals MH - Cell Division/drug effects MH - Diethylstilbestrol/*pharmacology MH - Embryonic and Fetal Development/*drug effects MH - Epidermal Growth Factor/*drug effects/metabolism MH - ErbB Receptors/drug effects/metabolism MH - Estrogens, Non-Steroidal/*pharmacology MH - Female MH - Immunoenzyme Techniques MH - Mullerian Ducts/cytology/*drug effects/embryology MH - Ovary/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Reverse Transcriptase Polymerase Chain Reaction MH - Uterus/metabolism EDAT- 2001/08/29 10:00 MHDA- 2001/10/05 10:01 CRDT- 2001/08/29 10:00 PHST- 2001/08/29 10:00 [pubmed] PHST- 2001/10/05 10:01 [medline] PHST- 2001/08/29 10:00 [entrez] AID - JOE04276 [pii] AID - 10.1677/joe.0.1700539 [doi] PST - ppublish SO - J Endocrinol. 2001 Sep;170(3):539-54. doi: 10.1677/joe.0.1700539.