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

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Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

Although the pubertal surge of estrogen is the immediate stimulus to mammary development, the action of estrogen depends upon the presence of pituitary growth hormone and the ability of GH to stimulate production of IGF-I in the mammary gland. Growth hormone binds to its receptor in the mammary fat pad, after which production of IGF-I mRNA and IGF-I protein occurs. It is likely that IGF-I then works through paracrine means to stimulate formation of TEBs, which then form ducts by bifurcating or trifurcating and extending through the mammary fat pad. By the time pubertal development is complete a tree-like structure of branching ducts fills the rodent mammary fat pad. In addition to requiring IGF-I in order to act, estradiol also directly synergizes with IGF-I to enhance formation of TEBs and ductal morphogenesis. Together they increase IRS-1 phosphorylation and cell proliferation, and inhibit apoptosis. In fact, the entire process of ductal morphogenesis, in oophorectomized IGF-I(−/−) knockout female mice, can occur as a result of the combined actions of estradiol and IGF-I. IGF-I also permits progesterone action in the mammary gland. Together they have been shown to stimulate a form of ductal morphogenesis, which is anatomically different from the kind induced by IGF-I and estradiol. Although both progesterone and estradiol synergize with IGF-I by increasing IGF-I action parameters, there must be other, as yet unknown mechanisms that account for the anatomical differences in the different forms of ductal morphogenesis observed (hyperplasia in response to IGF-I plus estradiol and single layered ducts in response to IGF-I plus progesterone).

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Abbreviations

GH:

growth hormone

PRL:

prolactin

hPRL:

human prolactin

PR:

progesterone receptor

E2 :

estradiol

ERα:

estrogen receptor α

TGF-β:

transforming growth factor beta

EGF:

epidermal growth factor

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Authors and Affiliations

  1. Neuroendocrine Unit, New York University School of Medicine, New York, NY, 10016, USA

    David L. Kleinberg & Weifeng Ruan

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  1. David L. Kleinberg
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  2. Weifeng Ruan
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Correspondence to David L. Kleinberg.

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From the Bunnie Joan Sachs Laboratory, VA Medical Center, New York, NY, USA

Supported in part by grants from DOD W81XWH-07-1-0488 and the Foundation for Growth and Endocrinology

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Kleinberg, D.L., Ruan, W. IGF-I, GH, and Sex Steroid Effects in Normal Mammary Gland Development. J Mammary Gland Biol Neoplasia 13, 353–360 (2008). https://doi.org/10.1007/s10911-008-9103-7

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