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

Hormonal mechanisms controlling growth of the fetus are poorly understood, and generally growth hormone (GH) is not thought to influence perinatal growth. To examine the influence of GH in the expression of genes in perinatal rat liver, we measured RNA levels of several GH responsive and growth axis genes. Spi 2.1, Spi 2.2, Spi 2.3, insulin-like growth factors (IGF) I and II, and GH receptor MRNAS were measured in rat 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 adult levels on day 2. Deoxyribonuclease I (Dnase I)-hypersensitive sites in the 5' flanking region of the Spi 2.1 gene, which are concordant with GH response, were not present in DNA extracted from livers at gestation day 19 but were present at days 20, 21, and 2, suggesting the gene is transcriptionally competent after day 19 and that the areas of chromatin vulnerable to DNase I digestion are the same in pre- and postnatal life. Low levels of GH receptor mRNAs (approximately 10% of adult) were present on all measured days. IGF-I mRNA was below quantitatable levels in day 19 or 20 fetal samples and was only 2.7 +/- 0.1% of adult 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 minimal increase at day 21 of gestation. In conclusion, expression of some GH responsive genes in the fetus reflects both availability of GH receptor and the known surge of GH in late fetal life. GH action may therefore participate in late fetal gene expression.