TRANSCRIPTIONAL AND POSTTRANSCRIPTIONAL REGULATION OF HEPATIC BETA-2-ADRENERGIC RECEPTOR GENE-EXPRESSION DURING DEVELOPMENT

Hepatic responsiveness to beta2-adrenergic stimulation is dynamically regulated during early development as well as following hepatic injury and disease. In the present study, the molecular mechanisms that unde rlie the decline in the steady-state levels of hepatic beta2-adrenergi c receptor mRNA that occurs during development in the male rat were in vestigated. As determined by nuclear run-on assays, an age-associated reduction in beta2-adrenergic receptor gene transcription was observed . The transcription rate of the beta2-adrenergic receptor gene in post natal day 18 liver was approximately 50% lower than that of fetal live r. Stability of beta2-adrenergic receptor gene transcripts was highest (t1/2 almost-equal-to 6 h) in hepatocytes isolated from fetal rats an d was lowest (t1/2 almost-equal-to 1 h) in hepatocytes isolated from p ostnatal day 14 rats. In fetal hepatocytes, but not postnatal day 2 he patocytes, cycloheximide appeared to stabilize beta2-adrenergic recept or gene transcripts in the presence of actinomycin D. These findings e stablish the molecular basis of reduced steady-state levels of beta2-a drenergic receptor mRNA in liver during early postnatal development an d suggest multilevel regulatory control of hepatic beta2-adrenergic re ceptor gene expression. (C) 1993 Wiley-Liss, Inc.