IGF-I: An Essential Factor in Terminal End Bud Formation and Ductal Morphogenesis

@article{Kleinberg2004IGFIAE,
  title={IGF-I: An Essential Factor in Terminal End Bud Formation and Ductal Morphogenesis},
  author={David L. Kleinberg and Mark Feldman and Weifeng Ruan},
  journal={Journal of Mammary Gland Biology and Neoplasia},
  year={2004},
  volume={5},
  pages={7-17}
}
Growth hormone (GH)3 is essential for rodent mammary gland development during puberty.It binds to GH receptors in the stromal compartment of the mammary gland and stimulatesIGF-I mRNA expression. These findings lead to the hypothesis that GH acts through locallyproduced IGF-I, which in turn, causes development of terminal end buds (TEBs), the structuresthat lead the process of mammary gland development during puberty. Subsequent studieshave in large measure proven this hypothesis. They include… 

IGF-I, GH, and Sex Steroid Effects in Normal Mammary Gland Development

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A role for the IGFs and IGFBPs are supported as local mediators of postnatal mammary gland growth and differentiation in mice mammary glands in organ culture.

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Important functions for the family of IGFBPs during postnatal growth and differentiation of the mammary epithelium are suggested.

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  • D. YeeT. Wood
  • Biology, Medicine
    Journal of Mammary Gland Biology and Neoplasia
  • 2008
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IGF and Insulin Action in the Mammary Gland: Lessons from Transgenic and Knockout Models

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Insulin-Like Growth Factor I Is Essential for Terminal End Bud Formation and Ductal Morphogenesis during Mammary Development1.

The present study shows that, even when GH is present, no mammary development is possible unless IGF-I is present.

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

It is demonstrated that IGF-I and IGFBP-3 may modulate the involutionary process of the lactating mammary gland by influencing the remodeling of mammary tissue during involution.

Evidence that the mammary fat pad mediates the action of growth hormone in mammary gland development.

Data indicate that bGH works as well on mammary stromal tissue as on tissue with glands and suggests that GH acts on theStromal compartment of the mammary gland to induce IGF-I mRNA and possibly IGF- I itself, which, in turn, causes differentiation of epithelial ducts into terminal end buds.

Evidence that the growth hormone receptor mediates differentiation and development of the mammary gland.

It is shown that nonlactogenic rat (r) GH is far more potent than rPRL in inducing rat mammary development, suggesting that GH receptors play a central role in this process.

Estradiol enhances the stimulatory effect of insulin-like growth factor-I (IGF-I) on mammary development and growth hormone-induced IGF-I messenger ribonucleic acid.

These studies indicate that IGF-I can have a small independent effect on mammary development, but like GH, E2 is required for a full effect, and that the action of E2 on Mammary development may take place at multiple sites.

The Insulin-Like Growth Factors (IGF) and IGF Type I Receptor during Postnatal Growth of the Murine Mammary Gland: Sites of Messenger Ribonucleic Acid Expression and Potential Functions* * This work was supported, in part, by NIH Grant DK-48103 (to T.L.W.).

In situ hybridization analyses determined that IGF-I, IGF-II, and IGF-IR messenger RNAs were expressed in the highly proliferative terminal end buds during pubertal ductal growth and correlated with the pattern of rapidly proliferating cells, suggesting a potential autocrine or paracrine role for IGF- II as a mitogen for ductal epithelial cells.

Early Mammary Development: Growth Hormone and IGF-1

  • D. Kleinberg
  • Biology
    Journal of Mammary Gland Biology and Neoplasia
  • 2004
This minireview focuses on the hormonal control of early mammary development with special emphasis on the roles of growth hormone and IGF-1.

Differential expression of the growth hormone receptor and growth hormone-binding protein in epithelia and stroma of the mouse mammary gland at various physiological stages.

GHR and GHBP mRNAs and proteins are expressed in both the epithelium and the stroma of mammary glands of virgin, pregnant, and lactating mice and indicate that the actions of GH in the mammary gland are both direct through its binding tothe epithelia, and indirect by binding to theStroma and stimulation of IGF-I production which, in turn, affects mammary epithelial development.