Epithelial-specific and stage-specific functions of insulin-like growth factor-I during postnatal mammary development.
Postnatal development of the mammary gland requires interactions between the epithelial and stromal compartments, which regulate actions of hormones and growth factors. IGF-I is expressed in both epithelial and stromal compartments during postnatal development of the mammary gland. However, little is known about how local expression of IGF-I in epithelium or stroma regulates mammary growth and differentiation during puberty and pregnancy-induced alveolar development. The goal of this study was to investigate the mechanisms of IGF-I actions in the postnatal mammary gland and test the hypothesis that IGF-I expressed in stromal and epithelial compartments has distinct functions. We established mouse lines with inactivation of the igf1 gene in mammary epithelium by crossing igf1/loxP mice with mouse lines expressing Cre recombinase under the control of either the mouse mammary tumor virus long-terminal repeat or the whey acidic protein gene promoter. Epithelial-specific loss of IGF-I during pubertal growth resulted in deficits in ductal branching. In contrast, heterozygous reduction of IGF-I throughout the gland decreased expression of cyclins A2 and B1 during pubertal growth and resulted in alterations in proliferation of the alveolar epithelium and milk protein levels during pregnancy-induced differentiation. Reduction in epithelial IGF-I at either of these stages had no effect on these indices. Taken together, our results support distinct roles for IGF-I expressed in epithelial and stromal compartments in mediating growth of the postnatal mammary gland.
Loladze
Aimee V
AV
Department of Neural and Behavioral Sciences, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.
Stull
Malinda A
MA
Rowzee
Anne M
AM
Demarco
Jean
J
Lantry
James H
JH
Rosen
Clifford J
CJ
Leroith
Derek
D
Wagner
Kay-Uwe
KU
Hennighausen
Lothar
L
Wood
Teresa L
TL
D000818:Animals; D002364:Caseins / Q000235:genetics; D016213:Cyclins / Q000235:genetics; D004848:Epithelium / Q000502:physiology; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D019426:Integrases / Q000502:physiology; D008321:Mammary Glands, Animal / Q000254:growth & development*; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000032:analysis; D011995:Recombination, Genetic; D012741:Sexual Maturation / Q000502:physiology; D017154:Stromal Cells / Q000502:physiology
D002364:Caseins; D016213:Cyclins; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; C045073:Cre recombinase; D019426:Integrases