IMMUNOLOCALIZATION AND EXPRESSION OF INSULIN-LIKE GROWTH-FACTOR-I (IGF-I) IN THE MAMMARY-GLAND DURING RAT GESTATION AND LACTATION

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 determin ed in mammary gland and liver by slot-blotting. A sensitive and IGF-I- specific ribonuclease (RNAse) protection assay was further used to det ect RNAs transcribed from the IGF-I gene. In the first half of pregnan cy, the maternal serum IGF-I concentration rises while the IGF-BP leve l decreases. This may modify IGF-I availability, thus promoting rapid tissue growth and differentiation. In the second half of pregnancy, th e 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-partu m, serum IGF-I increases back to the level obtained in non-pregnant co ntrols within 5 days. Serum levels of IGF-BP, during the same two peri ods, 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 dimin ishes. In the liver, on the other hand, expression increases during ve ry early pregnancy and diminishes thereafter, remaining below the leve l measured in non-pregnant animals from mid-pregnancy to term. The pat tern of IGF-BP3 expression followed was similar in both organs, with a decrease during gestation. In lactating animals, expression of both t he IGF-I and IGF-BP3 genes remains stable in the liver, at the level r eached in late pregnancy. Not so in the mammary gland, where expressio n of both genes drops sharply. IGF-I was immunolocalized in the mammar y gland to myoepithelial cells in non-pregnant, pregnant, and lactatin g animals. Our data suggest that IGF-I, both produced within the mamma ry 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, o n the other hand, is probably produced in the maternal liver rather th an in the mammary gland.