A local increase in the mammary IGF-1: IGFBP-3 ratio mediates the mammogenic effects of estrogen and growth hormone.
A single epithelium-free mammary fat pad was surgically prepared in each of twenty-five one-month-old, Friesian heifers. At 18 mo of age, heifers were randomly assigned to one of four treatment groups. Treatments were: control (C), growth hormone (GH), estrogen (E) or growth hormone + estrogen (GE). Hormones were administered for 40 hr before the animals were sacrificed to provide mammary samples of parenchyma (PAR), intact fat pad (MFP), and epithelium-free or "cleared" fat pad (CFP). IGF-1 and IGF binding protein-3 (IGFBP-3) mRNA was highest in CFP and MFP whereas the protein products were highest in PAR. IGFBP-2, a 28-kDa IGFBP and a 24-kDa IGFBP were more abundant in CFP and MFP. E and GH increased incorporation of [(3)H]thymidine into DNA of PAR. Incorporation of [(3)H]thymidine into the DNA of MFP or CFP was minimal. Coincident with the changes observed in mammary epithelial proliferation, E increased IGF-1 protein in MFP and PAR, and to a lesser extent in CFP. E tended to increase IGF-1 mRNA levels in MFP, but not CFP implying that the regulation of IGF-1 expression is modulated by adjacent epithelium. GH and E reduced IGFBP-3 protein in PAR and increased the 24-kDa IGFBP in CFP and MFP. Increased proliferation of mammary parenchymal cells was associated with increased IGF-1 and reduced IGFBP-3 protein in mammary tissue. An increase in the ratio of mammary IGF-1: IGFBP-3 likely increases the proportion of the mammary IGF-1 available to stimulate proliferation. These data also indicate that stromal: epithelial interactions regulate the IGF-1 axis in mammary tissue.
Berry
S D
SD
Dairy Science Group, AgResearch, Ruakura Research Centre, Hamilton, New Zealand.
McFadden
T B
TB
Pearson
R E
RE
Akers
R M
RM
D000818:Animals; D015152:Blotting, Northern / Q000662:veterinary; D015153:Blotting, Western / Q000662:veterinary; D002417:Cattle / Q000378:metabolism*; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D004967:Estrogens / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D005260:Female; D013006:Growth Hormone / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis* / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000096:biosynthesis*; D008321:Mammary Glands, Animal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay / Q000662:veterinary; D011897:Random Allocation; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D013936:Thymidine / Q000032:analysis / Q000737:chemistry
D004967:Estrogens; D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D013936:Thymidine