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Expression of ovine insulin-like growth factor-1 (IGF-1) stimulates alveolar bud development in mammary glands of transgenic mice

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Abstract

To determine whether murine mammary growth is modulated by local insulin-like growth factor-1 (IGF-1) production, expression of recombinant IGF-1 was directed to the mammary glands of transgenic mice using an ovine prepro IGF-1 cDNA under control of the mouse mammary tumor virus-long terminal repeat (MMTV-LTR) promoter. Bioactivity of recombinant IGF-1 in transgenic mouse milk extracts was demonstrated by a concentration-dependent increase in [3H]thymidine incorporation in clonal bovine mammary epithelial cells (MAC-T) compared with control mouse milk extracts; moreover, addition of excess recombinant human insulin-like growth factor binding protein-3 (rhIGFBP-3) abolished the increase in [3H]thymidine incorporation attributed to recombinant IGF-1 in transgenic mouse milk. Recombinant IGF-1 was produced in mammary tissue of virgin and pregnant transgenic mice, and secreted into milk of lactating mice. However, recombinant IGF-1 was not detected in serum from transgenic mice; and ligand blot analysis of serum insulin-like growth factor binding proteins (IGFBPs) indicated no differences owing to transgene presence. In peripubertal virgin mice at 49 d of age, the frequency of appearance of mammary alveolar buds was significantly higher in MMTV-IGF-1 than in CD-1 mice, and was unaffected by ovariectomy or estradiol treatment. In conclusion, mammary synthesis of recombinant IGF-1 enhances the rate of development of alveolar buds in mammary glands of virgin transgenic mice.

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Authors and Affiliations

  1. Department of Dairy Science, Virginia Polytechnic Institute and State University, Blacksburg, VA

    Miriam S. Weber, Patricia L. Boyle, Benjamin A. Corl, Frank C. Gwazdauskas &  R. Michael Akers

  2. Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA

    Eric A. Wong

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  1. Miriam S. Weber
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  2. Patricia L. Boyle
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  3. Benjamin A. Corl
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  4. Eric A. Wong
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  5. Frank C. Gwazdauskas
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  6. R. Michael Akers
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Correspondence to R. Michael Akers.

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Weber, M.S., Boyle, P.L., Corl, B.A. et al. Expression of ovine insulin-like growth factor-1 (IGF-1) stimulates alveolar bud development in mammary glands of transgenic mice. Endocr 8, 251–259 (1998). https://doi.org/10.1385/ENDO:8:3:251

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  • DOI: https://doi.org/10.1385/ENDO:8:3:251

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