The ontogeny of apolipoprotein expression in rat liver. mRNA levels in developing liver and cultured fetal rat hepatocytes.
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.
Hall
G P
GP
Department of Physiology, University of Western Australia, Nedlands.
Redgrave
T G
TG
Yeoh
G C
GC
D000367:Age Factors; D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics; D001053:Apolipoproteins / Q000235:genetics*; D001054:Apolipoproteins A / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D002478:Cells, Cultured; D005260:Female; D005333:Fetus / Q000378:metabolism*; D006728:Hormones / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017208:Rats, Wistar
D016632:Apolipoprotein A-I; D001053:Apolipoproteins; D001054:Apolipoproteins A; D001057:Apolipoproteins E; D006728:Hormones; D012333:RNA, Messenger; C022205:apolipoprotein A-IV