Involution of the lactating mammary gland is inhibited by the IGF system in a transgenic mouse model

Stefan Neuenschwander, Arnold Schwartz, Teresa L. Wood, Charles T. Roberts, Lothar Henninghausen, Derek LeRoith

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    168 Scopus citations


    Development of the mammary gland during puberty, pregnancy, and lactation is controlled by steroid and peptide hormones and growth factors. To determine the role of the insulin-like growth factors (IGFs) in this process we developed a transgenic model using the whey acidic protein (WAP) gene to direct expression of rat IGF-I and human IGF binding protein-3 (IGFBP-3) to mammary tissue during late pregnancy and throughout lactation. High levels of expression of transgenic IGF-I and IGFBP-3 were seen in lobular-alveolar cells by in situ hybridization. There was no obvious effect on mammary development during pregnancy and lactation; indeed, mothers were capable of nursing their pups normally and the only structural difference seen in the mammary glands at peak lactation was an overall smaller size of the alveoli. We also evaluated the role of IGF-I and IGFBP-3 in the remodeling of mammary tissue during involution. Compared with control animals, the process of involution was modified in both transgenic lines. The degree of apoptotic cells was lower in the WAP-IGF-I and WAP-BP-3 expressing mice. In addition, there was a more quiescent pattern of involution with residual lobular secretory ability and a muted host inflammatory reaction with fewer lumenal microcalcifications. These results demonstrate that IGF-I and IGFBP-3 may modulate the involutionary process of the lactating mammary gland.

    Original languageEnglish (US)
    Pages (from-to)2225-2232
    Number of pages8
    JournalJournal of Clinical Investigation
    Issue number10
    StatePublished - May 15 1996


    • apoptosis
    • insulin-like growth factors
    • lactation
    • transgenic whey acidic protein gene

    ASJC Scopus subject areas

    • Medicine(all)

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