Expression of ovine insulin-like growth factor-1 (IGF-1) stimulates alveolar bud development in mammary glands of transgenic mice.
To determine whether murine mammary growth is modulated by local insulin-like growth factor-1 (IGF-1) production, expression of recombinant IGF-1 was directed to the mammary glands of transgenic mice using an ovine prepro IGF-1 cDNA under control of the mouse mammary tumor virus-long terminal repeat (MMTV-LTR) promoter. Bioactivity of recombinant IGF-1 in transgenic mouse milk extracts was demonstrated by a concentration-dependent increase in [3H]thymidine incorporation in clonal bovine mammary epithelial cells (MAC-T) compared with control mouse milk extracts; moreover, addition of excess recombinant human insulin-like growth factor binding protein-3 (rhlGFBP-3) abolished the increase in [3H]thymidine incorporation attributed to recombinant IGF-1 in transgenic mouse milk. Recombinant IGF-1 was produced in mammary tissue of virgin and pregnant transgenic mice, and secreted into milk of lactating mice. However, recombinant IGF-1 was not detected in serum from transgenic mice; and ligand blot analysis of serum insulin-like growth factor binding proteins (IGFBPs) indicated no differences owing to transgene presence. In peripubertal virgin mice at 49 d of age, the frequency of appearance of mammary alveolar buds was significantly higher in MMTV-IGF-1 than in CD-1 mice, and was unaffected by ovariectomy or estradiol treatment. In conclusion, mammary synthesis of recombinant IGF-1 enhances the rate of development of alveolar buds in mammary glands of virgin transgenic mice.
Weber
M S
MS
Department of Dairy Science, Virginia Polytechnic Institute and State University, Blacksburg, USA.
Boyle
P L
PL
Corl
B A
BA
Wong
E A
EA
Gwazdauskas
F C
FC
Akers
R M
RM
D000818:Animals; D002417:Cattle; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008321:Mammary Glands, Animal / Q000254:growth & development*; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D012756:Sheep; D020079:Terminal Repeat Sequences / Q000235:genetics; D013936:Thymidine / Q000378:metabolism; D019076:Transgenes
D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D013936:Thymidine