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Evaluation of murine placental degradation and transfer of (/sup 125/I)iodo-epidermal growth factor

Journal Article · · Endocrinology; (United States)
OSTI ID:6937452
Since epidermal growth factor (EGF) has been postulated to play a role in embryonic and fetal growth, a study was undertaken to assess the placental degradation and transfer of maternally administered EGF. Approximately 5 ng of purified (/sup 125/I)iodo-EGF were injected iv into day 10, day 13, or day 17 pregnant CD-1 mice; radioactivity in plasma, placentas, and conceptuses was measured up to 2 h after injection. The time course analysis revealed an initial rapid decline in total plasma radioactivity followed by an increase that was maximal by approximately 30 min. Gel filtration (G-15, G-50) chromatography of plasma revealed that by 5 min, radioactivity was associated with free /sup 125/I and with material much larger than EGF. No apparent degradation of (/sup 125/I)iodo-EGF occurred after direct incubation with maternal plasma. Placental radioactivity had an initial phase of decay between 1 and 5 min followed by an increase that became maximal between 30 and 60 min. Extracts of placentas made with 4 M urea in 0.2 M Tris-HCl, pH 8.0, and taken 1-30 min after injection revealed radioactivity coeluting predominantly with (/sup 125/I)iodo-EGF at 1 min but shifting to mostly free /sup 125/I by 30 min. Uptake of radioactivity by conceptuses was not evident until about 15 min, and only free /sup 125/I was detected in extracts; the same results were obtained when 5 micrograms unlabeled EGF were injected simultaneously with (/sup 125/I)iodo-EGF. Incubation of placental mince with (/sup 125/I)iodo-EGF yielded (/sup 125/I)MIT as the apparent major radioactive degradation product. Formation of (/sup 125/I)MIT in vitro was both time- and temperature-dependent. At 37 C, marked formation of (/sup 125/I)MIT was observed; at 22 C, only a negligible amount was formed after incubation of mince with (/sup 125/I)iodo-EGF for 60 min. Incubation of (/sup 125/I)iodo-EGF with kidney mince yielded predominantly free /sup 125/I.
Research Organization:
National Institute of Environmental Health Sciences, Research Triangle Park, NC
OSTI ID:
6937452
Journal Information:
Endocrinology; (United States), Journal Name: Endocrinology; (United States) Vol. 3; ISSN ENDOA
Country of Publication:
United States
Language:
English