EXPRESSION OF GROWTH HORMONE-RESPONSIVE SERPIN MESSENGER-RNAS IN PERINATAL RAT-LIVER

Hormonal mechanisms controlling growth of the fetus are poorly underst ood, and generally growth hormone (GH) is not thought to influence per inatal growth. To examine the influence of GH in the expression of gen es in perinatal rat liver, we measured RNA levels of several GH respon sive and growth axis genes. Spi 2.1, Spi 2.2, Spi 2.3, insulin-like gr owth factors (IGF) I and II, and GH receptor MRNAS were measured in ra t liver total RNA from gestational days 19, 20, 21, and postnatal day 2. Spi 2.1 and 2.3 genes were faintly expressed on day 20, 6% and 13 /- 1% of adult levels on gestation day 21, and 6% and 31 +/- 6% of adu lt levels on day 2. Deoxyribonuclease I (Dnase I)-hypersensitive sites in the 5' flanking region of the Spi 2.1 gene, which are concordant w ith GH response, were not present in DNA extracted from livers at gest ation day 19 but were present at days 20, 21, and 2, suggesting the ge ne is transcriptionally competent after day 19 and that the areas of c hromatin vulnerable to DNase I digestion are the same in pre- and post natal life. Low levels of GH receptor mRNAs (approximately 10% of adul t) were present on all measured days. IGF-I mRNA was below quantitatab le levels in day 19 or 20 fetal samples and was only 2.7 +/- 0.1% of a dult levels on day 21. Levels on day 2 were 9.6 +/- 1.9% of adult. IGF -II mRNA was essentially constant throughout this period, with a minim al increase at day 21 of gestation. In conclusion, expression of some GH responsive genes in the fetus reflects both availability of GH rece ptor and the known surge of GH in late fetal life. GH action may there fore participate in late fetal gene expression.