Transcriptional and posttranscriptional regulation of hepatic beta 2-adrenergic receptor gene expression during development.
Hepatic responsiveness to beta 2-adrenergic stimulation is dynamically regulated during early development as well as following hepatic injury and disease. In the present study, the molecular mechanisms that underlie the decline in the steady-state levels of hepatic beta 2-adrenergic receptor mRNA that occurs during development in the male rat were investigated. As determined by nuclear run-on assays, an age-associated reduction in beta 2-adrenergic receptor gene transcription was observed. The transcription rate of the beta 2-adrenergic receptor gene in postnatal day 18 liver was approximately 50% lower than that of fetal liver. Stability of beta 2-adrenergic receptor gene transcripts was highest (t1/2 approximately 6h) in hepatocytes isolated from fetal rats and was lowest (t1/2 approximately 6h) in hepatocytes from postnatal day 14 rats. In fetal hepatocytes, but not postnatal day 2 hepatocytes, cycloheximide appeared to stabilize beta 2-adrenergic receptor gene transcripts in the presence of actinomycin D. These findings establish the molecular basis of reduced steady-state levels of beta 2-adrenergic receptor mRNA in liver during early postnatal development and suggest multilevel regulatory control of hepatic beta 2-adrenergic receptor gene expression.
Baeyens
D A
DA
Department of Biology, Univerisity of Arkansas, Little Rock 72204.
Cornett
L E
LE
D000818:Animals; D000831:Animals, Newborn; D015152:Blotting, Northern; D002478:Cells, Cultured; D018076:DNA, Complementary; D005314:Embryonic and Fetal Development; D005260:Female; D005333:Fetus / Q000378:metabolism* / Q000502:physiology; D005786:Gene Expression Regulation; D008099:Liver / Q000166:cytology / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000235:genetics*; D014158:Transcription, Genetic
D018076:DNA, Complementary; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta