Role of IGF-I in normal mammary development

  title={Role of IGF-I in normal mammary development},
  author={David L. Kleinberg},
  journal={Breast Cancer Research and Treatment},
  • D. Kleinberg
  • Published 1 February 1998
  • Biology
  • Breast Cancer Research and Treatment
Growth hormone (GH) is now believed to be the pituitary factor that is responsible for mammary ductal morphogenesis. Mammary development at puberty occurs because of synergy between GH and estrogen on formation of terminal end buds (TEBs). TEBs extend into the substance of the mammary gland fat pad, resulting in ductal morphogenesis. Ultimately, the whole mammary fat pad accommodates a complex network of ducts. IGF-I or des(1-3) IGF-I mimic the actions of GH on TEB formation in… 

Growth hormone and insulin-like growth factor-I in the transition from normal mammary development to preneoplastic mammary lesions.

It is possible that inhibition of IGF-I action, or perhaps GH, in the mammary gland may eventually play a role in breast cancer chemoprevention by preventing actions of both estrogen and progesterone, especially in women at extremely high risk for developing breast cancer such as BRCA gene 1 or 2 mutations.

The Insulin-Like Growth Factors (IGFs) and IGF Binding Proteins in Postnatal Development of Murine Mammary Glands

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.

Mammary gland branching morphogenesis is diminished in mice with a deficiency of insulin-like growth factor-I (IGF-I), but not in mice with a liver-specific deletion of IGF-I.

It is proposed that paracrine, not endocrine, IGF-I is important for mammary branching morphogenesis, and that GH is required for Mammary gland ductal morphogenesis.

Elevated circulating IGF-I promotes mammary gland development and proliferation.

Animal studies have shown that IGF-I is essential for mammary gland development. Previous studies have suggested that local IGF-I rather than circulating IGF-I is the major mediator of mammary gland

Expression of the IGFs, IGF-IR and IGFBPs in the normal mammary gland and breast.

Data on local expression of the IGFs, IGF receptors and IGFBPs is reviewed and the possible roles for these molecules in normal growth of mammary and breast tissue are discussed.

IGF-2 is a mediator of prolactin-induced morphogenesis in the breast.

Developmental Changes in Insulin‐like Growth Factor I Receptor Gene Expression in the Mouse Mammary Gland

Results demonstrate that a developmental IGF‐IR gene expression pattern exists in the mouse mammary gland and that increases in gene expression at specific phases of development may reflect an important role for IGF‐I/IGF‐IR at those phases ofDevelopment.

Obesity Alters Gene Expression for GH/IGF-I Axis in Mouse Mammary Fat Pads: Differential Role of Cortistatin and Somatostatin

The results offer new information on the factors (GH/IGF-I axis) involved in the endocrine/metabolic dysregulation of MFPs in obesity, and suggest that CORT is not a mere SST sibling in regulating MG physiology.

IGF and Insulin Action in the Mammary Gland: Lessons from Transgenic and Knockout Models

Results obtained from the application of transgenic and knockout mice to determine the roles of insulin and insulin-like growth factors (IGF)3 in the regulation of mammary gland development, lactation and tumorigenesis are focused on.



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.

Intact and amino-terminally shortened forms of insulin-like growth factor I induce mammary gland differentiation and development.

The findings suggest that the inductive effect of GH on glandular differentiation is mediated by the GH-induced production of IGF-I or a related molecule within the mammary gland itself.

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.

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.

Primate mammary development. Effects of hypophysectomy, prolactin inhibition, and growth hormone administration.

It is found that physiological or slightly supraphysiological concentrations of hGH in animals with unmeasurable prolactin were incapable of restoring the capacity of E2 to induce full mammary growth and the possibility that heretofore unidentified pituitary substances may be mammogenic.

Targeted expression of des(1-3) human insulin-like growth factor I in transgenic mice influences mammary gland development and IGF-binding protein expression.

Histological analysis of mammary tissue from mice overexpressing des(1-3)hIGF-I showed incomplete mammary involution, ductile hypertrophy, and loss of secretory lobules associated with increased deposition of collagen, believed to occur through autocrine and paracrine effects of des( 1-3)-hIGf-I on both epithelial and stromal cells.

Mammary gland development with mammogen I in the castrate and the hypophysectomized rat.

IN 1936, REECE et al. (1) published the first experiments showing that the mammary glands of completely hypophysectomized animals did not respond to administration of ovarian hormones. Gomez and

Regulation by growth hormone of number of chondrocytes containing IGF-I in rat growth plate.

The findings suggest that IGF-I has a specific role in the clonal expansion of differentiated chondrocytes and exerts its function locally through autocrine or paracrine mechanisms.