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• W2040988043 abstract "Neonatal males develop respiratory distress syndrome more frequently than females for unknown reasons. The fetal testis secretes testosterone and müllerian inhibiting substance (MIS); MIS has been shown to inhibit fetal lung maturation in vitro and in vivo and to block phosphorylation of epidermal growth factor (EGF) receptors in A431 cells. We hypothesized that MIS would also inhibit membrane phosphorylation of EGF receptors in fetal lung, and that ultrastructural study of MIS-exposed lung might complement the biochemical data by assessing the effect of MIS on tissue morphology. Lung membranes were prepared from 19.5-day fetal rats and phosphorylation assays performed with 3 to 4 μg of membrane protein, with or without EGF (26 nmol/L), 0.025 mCi AT32P (0.136 μmol/L), and either recombinant human MIS (rhMIS, 30 pmol) from media of Chinese hamster ovary (CHO) cells, rhMIS dialysis buffer, or wild-type CHO media. The 170,000 molecular weight EGF receptor, visualized by autoradiography of polyacrylamide gels, was phosphorylated in both female and male membranes. rhMIS, when added to EGF-stimulated membranes, caused significant inhibition of EGF receptor phosphorylation (females: 32.42% ± 11.5%; males: 32.3% ± 19.1%, P < 0.001; rhMIS-treated v EGF-stimulated state, P = NS, male v female, Cerenkov counting). Electron microscopy (EM) of rhMIS-exposed lung showed decreased lamellar bodies (LB) in both male alveolar spaces and female parenchyma, and, unexpectedly, increased numbers in female alveoli. Immunoabsorption experiments using coincubation of rhMIS with anti-rhMIS IgG polyclonal antibodies or equiprotein normal IgG demonstrated MIS antibody-specific reversal of rhMIS activity in membrane phosphorylation. These observations in fetal rat lung membranes extend the previous data showing inhibitory effects by MIS in fetal lung, confirm findings in natural tissue previously confined to tumor cells (A431), and suggest that rhMIS signal transduction could be mediated via inhibition of EGF receptor autophosphorylation." @default.
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• W2040988043 date "1991-11-01" @default.
• W2040988043 modified "2023-10-18" @default.
• W2040988043 title "Müllerian inhibiting substance blocks epidermal growth factor receptor phosphorylation in fetal rat lung membranes" @default.
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• W2040988043 doi "https://doi.org/10.1016/0026-0495(91)90213-g" @default.
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