1. Androgen Regulation of Signaling Pathways in Late Fetal Mouse Lung Development1
- Author
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Christiane E.L. Dammann, Lucia D. Pham, Dana McCants, Sujatha M. Ramadurai, and Heber C. Nielsen
- Subjects
medicine.medical_specialty ,biology ,medicine.drug_class ,Growth factor ,medicine.medical_treatment ,Androgen ,Endocrinology ,Internal medicine ,Dihydrotestosterone ,medicine ,biology.protein ,Pulmonary surfactant-associated protein B ,Epidermal growth factor receptor ,Signal transduction ,Receptor ,Transforming growth factor ,medicine.drug - Abstract
During lung development there is tension between positive and negative regulators of fibroblast-epithelial communication controlling type II cell differentiation. A clinical consequence of imbalance of this tension is the increased risk for respiratory distress syndrome in male infants. We hypothesized that chronic intrauterine androgen exposure alters fetal lung fibroblast maturation by down-regulating epidermal growth factor receptor (EGF-R) activity and by up-regulating transforming growth factor-β receptor (TGFβ-R) activity, leading to an inhibition of surfactant protein B (SP-B) and -C (SP-C) gene expression in type II cells. We treated pregnant mice with dihydrotestosterone (DHT; 2 mg/day) or vehicle for 7 days, starting on gestational day 11. On day 18, EGF binding, EGF-R phosphorylation, TGFβ-R binding, and TGFβ1-induced cell proliferation were studied in sex-specific fibroblast cultures. SP-B and -C messenger RNA levels were measured in whole lungs. Chronic DHT treatment reduced both EGF binding ...
- Published
- 2000