Epithelial-specific and stage-specific functions of insulin-like growth factor-I during postnatal mammary development

Endocrinology. 2006 Nov;147(11):5412-23. doi: 10.1210/en.2006-0427. Epub 2006 Aug 10.


Postnatal development of the mammary gland requires interactions between the epithelial and stromal compartments, which regulate actions of hormones and growth factors. IGF-I is expressed in both epithelial and stromal compartments during postnatal development of the mammary gland. However, little is known about how local expression of IGF-I in epithelium or stroma regulates mammary growth and differentiation during puberty and pregnancy-induced alveolar development. The goal of this study was to investigate the mechanisms of IGF-I actions in the postnatal mammary gland and test the hypothesis that IGF-I expressed in stromal and epithelial compartments has distinct functions. We established mouse lines with inactivation of the igf1 gene in mammary epithelium by crossing igf1/loxP mice with mouse lines expressing Cre recombinase under the control of either the mouse mammary tumor virus long-terminal repeat or the whey acidic protein gene promoter. Epithelial-specific loss of IGF-I during pubertal growth resulted in deficits in ductal branching. In contrast, heterozygous reduction of IGF-I throughout the gland decreased expression of cyclins A2 and B1 during pubertal growth and resulted in alterations in proliferation of the alveolar epithelium and milk protein levels during pregnancy-induced differentiation. Reduction in epithelial IGF-I at either of these stages had no effect on these indices. Taken together, our results support distinct roles for IGF-I expressed in epithelial and stromal compartments in mediating growth of the postnatal mammary gland.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Caseins / genetics
  • Cyclins / genetics
  • Epithelium / physiology
  • Female
  • Insulin-Like Growth Factor I / analysis
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / physiology*
  • Integrases / physiology
  • Mammary Glands, Animal / growth & development*
  • Mammary Tumor Virus, Mouse / genetics
  • Mice
  • Mice, Transgenic
  • RNA, Messenger / analysis
  • Recombination, Genetic
  • Sexual Maturation / physiology
  • Stromal Cells / physiology


  • Caseins
  • Cyclins
  • RNA, Messenger
  • Insulin-Like Growth Factor I
  • Cre recombinase
  • Integrases