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

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Abstract

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 the observations that mammarydevelopment was grossly impaired in female mice deficient in IGF-I (IGF-I(−/−) knockoutmice), and treatment of these mice with IGF-I plus estradiol (E2) restored pubertal mammarydevelopment while treatment with GH + E2 did not. Thus, the full phenotypic action of GHin mammary gland development is mediated by IGF-I. We have demonstrated one effect ofGH on the mammary gland that does not appear to be mediated by the action of IGF-I. GHincreased the level of estrogen receptor (ER) mRNA and protein in the nuclei of mammaryfat pad cells, but IGF-I did not. In addition to the critical role of the GH/IGF-I axis duringpubertal mammary development, other data suggest that IGF-I might also be of importanceduring pregnancy and lactation. In summary, the earliest phase of pubertal mammarydevelopment (formation of TEBs) requires IGF-I or GH in IGF-I sufficient animals. No other hormoneshave been shown to stimulate formation of TEBs unless GH or IGF-I is present. GH-inducedIGF-I is of major importance in ductal morphogenesis, and may, in fact, be necessary for laterstages of mammary development, as well.

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Authors and Affiliations

  1. Departments of Medicine, New York University School of Medicine and Department of Veterans Affairs Medical Center, New York, New York, 10010

    David L. Kleinberg, Mark Feldman & Weifeng Ruan

  2. DVA Medical Center, Room 16043W, 423 E. 23 Street, New York, New York, 10010

    David L. Kleinberg

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  1. David L. Kleinberg
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  2. Mark Feldman
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  3. Weifeng Ruan
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Kleinberg, D.L., Feldman, M. & Ruan, W. IGF-I: An Essential Factor in Terminal End Bud Formation and Ductal Morphogenesis. J Mammary Gland Biol Neoplasia 5, 7–17 (2000). https://doi.org/10.1023/A:1009507030633

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