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This version published online on April 1, 2004
Endocrinology, doi:10.1210/en.2003-1112
A more recent version of this article appeared on July 1, 2004
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Submitted on August 26, 2003
Accepted on March 23, 2004

Mammary Gland Branching Morphogenesis is Diminished in Mice (IGF-Im/m) with a Deficiency of Insulin-like Growth Factor-I (IGF-I) but not in Mice with a Liver-specific Deletion of IGF-I

R. GREGG RICHARDS, DIANE M. KLOTZ, MICHAEL P. WALKER, and RICHARD P. DIAUGUSTINE*

Hormones and Cancer Group, Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709

* To whom correspondence should be addressed. E-mail: diaugus2{at}niehs.nih.gov.

The development of the mouse mammary gland occurs postnatally. Hormonal activation of local growth factor pathways stimulates rapid elongation and branching of the rudimentary gland through the fatty stroma. Earlier studies showed that growth hormone (GH) is required for mammary gland ductal morphogenesis and that IGF-I mediates this action of GH. In the present study, we show that adult IGF-Im/m mutant mice exhibit a marked reduction in levels of mammary gland and liver igf1 transcripts when compared with controls. Whole mounts of the adult IGF-Im/m mammary glands revealed ducts that extended to the limits of the fat pad; however, the number of bifurcation branch points in the ductal tree of the mutants was reduced by half when compared with that of wild-type glands. In contrast, adult mutant mice with a liver-specific deletion of the igf1 gene obtained by Cre/loxP recombination strategy maintained the normal levels of mammary gland igf1 transcripts and did not exhibit a branching deficit in this organ. It was previously reported that this specific loss of liver IGF-I causes serum levels of IGF-I (endocrine) to decrease by ~75%, while the levels of tissue igf1 transcripts remain unchanged. On the basis of these findings, we propose that paracrine, not endocrine, IGF-I is important for mammary branching morphogenesis.
Key words: Mammary gland • IGF-I • IGF-Im/m mouse • liver -specific IGF-I knockout mouse




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