Probing IUGR induced alterations in acid labile subunit

Intrauterine growth restriction (IUGR) is associated with a multitude of complications including an increased risk of developing adult insulin resistance. The mechanism behind this increased risk likely stems from epigenetic modifications. Acid labile subunit (ALS) is responsible for regulating the tissue bioavailability of IGF-1. IGF-1 bioavailability is vital in regulating myriad of functions, including adult glucose regulation. In this study western blotting was used to compare serum levels of ALS in IUGR rats to that of control animals. In addition, STAT5 occupancy of GH-response elements found in association with ALS and IGF-1 was used as a means of developing a chromatin immunoprecipitation (ChIP) assay to facilitate further exploration into the interactions between transcription factors and chromatin. Serum ALS protein levels were significantly increased in female rats at day 21 and at day 120. ALS serum protein levels in males were not significantly different in control and IUGR animals. Development of a fast ChIP assay gave some preliminary insight into differential occupancy of GH-response elements, by STAT5, where it appears that in female IUGR tissue there is a shift in occupancy toward the ALS regulatory element and away from one of the IGF-1 regulatory elements. In conclusion, it appears that female IUGR animals have greater levels of serum ALS and a potential shift in STAT5 binding of the ALS and IGF-1 response elements in favor of ALS expression. The improved ChIP assay reported here should help facilitate further investigation into the transcriptional regulation of ALS, IGF-1 and other important genes.