The Ontogeny of Apolipoprotein Expression in Rat Liver

Abstract

The pattern of apolipoprotein (apo) A‐I, A‐IV and E expression in developing rat liver was established by determining steady‐state levels of the respective mRNAs. Apo A‐I and A‐IV altered in a coordinate fashion; the transcripts were detected from day 13 of gestation, whereas apo E was first detected on day 19 of gestation. Apo A‐I and A‐IV mRNA levels increased with developmental age until day 19, then declined until birth, after which they increased. In contrast, apo E mRNA levels progressively increased from day‐13 gestation until 3 days postnatal at which time it reached adult levels. In cultured hepatocytes established from immature (15‐day gestation) and near‐term (19‐day gestation) fetuses the difference in regulation between apo A‐I and A‐IV and apo E was also observed. In 3‐day‐old fetal hepatocyte cultures established from 19‐day gestation rats, dexamethasone, insulin, thyroxine and glucagon each substantially increased levels of apo A‐I and A‐IV mRNA but markedly decreased apo E mRNA. Thus fetal and adult hepatocytes respond similarly to the hormones tested with respect to apolipoprotein expression. Unexpectedly, 15‐day gestation hepatocytes expressed apo E in culture, even without hormone supplementation. The discrepancy between in vivo and in vitro data suggests that, in the fetus, apo E expression may be suppressed by high levels of circulating steroid, insulin and thyroxine and that establishment of the hepatocytes in culture removes the inhibition, thereby inducing apo E expression in these immature cells. The data are also consistent with the view that the same group of hormones may be responsible for regulating levels of apo A‐I and A‐IV in the perinatal period. Both apolipoproteins progressively increase as the fetus reaches term at a time when these hormones which induce their expression are also increasing.