Immunolocalization and expression of insulin-like growth factor I (IGF-I) in the mammary gland during rat gestation and lactation

Abstract

We have studied the physiology and tissue expression of IGF-I and IGF-BP3 in pregnant and lactating rats. Specific assays (radioimmunoassays and a binding protein assay) were used to measure serum IGF-I, IGF-II, and IGF-BP levels. IGF-I and IGF-BP3 expression levels were determined in mammary gland and liver by slot-blotting. A sensitive and IGF-I-specific ribonuclease (RNAse) protection assay was further used to detect RNAs transcribed from the IGF-I gene. In the first half of pregnancy, the maternal serum IGF-I concentration rises while the IGF-BP level decreases. This may modify IGF-I availability, thus promoting rapid tissue growth and differentiation. In the second half of pregnancy, the mean serum IGF-I concentration falls sharply from 1140 ± 150 ng/ml at seven days of pregnancy to 470 ± 85 ng/ml at 20 days. Post-partum, serum IGF-I increases back to the level obtained in non-pregnant controls within 5 days. Serum levels of IGF-BP, during the same two periods, follow a similar pattern, decrease during pregnancy and increase after parturition. No IGF-II was detected at any time. From the onset of pregnancy to term, IGF-I gene expression in the mammary gland diminishes. In the liver, on the other hand, expression increases during very early pregnancy and diminishes thereafter, remaining below the level measured in non-pregnant animals from mid-pregnancy to term. The pattern of IGF-BP3 expression followed was similar in both organs, with a decrease during gestation. In lactating animals, expression of both the IGF-I and IGF-BP3 genes remains stable in the liver, at the level reached in late pregnancy. Not so in the mammary gland, where expression of both genes drops sharply. IGF-I was immunolocalized in the mammary gland to myoepithelial cells in non-pregnant, pregnant, and lactating animals. Our data suggest that IGF-I, both produced within the mammary gland and reaching it via the bloodstream, has a role in this organ's early development at the onset of pregnancy. IGF-I found in milk, on the other hand, is probably produced in the maternal liver rather than in the mammary gland.