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 Roberts, Lothar Henninghausen, Derek LeRoith

Research output: Contribution to journalArticle

166 Citations (Scopus)

Abstract

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
Volume97
Issue number10
StatePublished - May 15 1996
Externally publishedYes

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Somatomedins
Human Mammary Glands
Insulin-Like Growth Factor I
Transgenic Mice
Lactation
Insulin-Like Growth Factor Binding Proteins
Insulin-Like Growth Factor Binding Protein 3
Breast
Pregnancy
Alveolar Epithelial Cells
Calcinosis
Peptide Hormones
Puberty
In Situ Hybridization
Intercellular Signaling Peptides and Proteins
Nursing
Steroids
Genes
whey acidic proteins

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Neuenschwander, S., Schwartz, A., Wood, T. L., Roberts, C., Henninghausen, L., & LeRoith, D. (1996). Involution of the lactating mammary gland is inhibited by the IGF system in a transgenic mouse model. Journal of Clinical Investigation, 97(10), 2225-2232.

Involution of the lactating mammary gland is inhibited by the IGF system in a transgenic mouse model. / Neuenschwander, Stefan; Schwartz, Arnold; Wood, Teresa L.; Roberts, Charles; Henninghausen, Lothar; LeRoith, Derek.

In: Journal of Clinical Investigation, Vol. 97, No. 10, 15.05.1996, p. 2225-2232.

Research output: Contribution to journalArticle

Neuenschwander, S, Schwartz, A, Wood, TL, Roberts, C, Henninghausen, L & LeRoith, D 1996, 'Involution of the lactating mammary gland is inhibited by the IGF system in a transgenic mouse model', Journal of Clinical Investigation, vol. 97, no. 10, pp. 2225-2232.
Neuenschwander S, Schwartz A, Wood TL, Roberts C, Henninghausen L, LeRoith D. Involution of the lactating mammary gland is inhibited by the IGF system in a transgenic mouse model. Journal of Clinical Investigation. 1996 May 15;97(10):2225-2232.
Neuenschwander, Stefan ; Schwartz, Arnold ; Wood, Teresa L. ; Roberts, Charles ; Henninghausen, Lothar ; LeRoith, Derek. / Involution of the lactating mammary gland is inhibited by the IGF system in a transgenic mouse model. In: Journal of Clinical Investigation. 1996 ; Vol. 97, No. 10. pp. 2225-2232.
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