Transcription-dependent and -independent regulation of hepatic ornithine decarboxylase activity by CNS beta-endorphin in rat pups.
We have previously shown that intracerebroventricular administration of relatively low doses of beta-endorphin suppresses basal levels of hepatic ODC activity as well as tissue ODC responsiveness to administered insulin in developing rats. Using Northern blotting analysis, the current studies examine whether these effects of CNS beta-endorphin may be mediated by changes in ODC gene expression. Subcutaneous administration of insulin (20 IU/kg body weight) rapidly and profoundly increased liver ODC activity. The time course of the response was characterized by proportionally increased levels of ODC mRNA, suggesting that insulin-induced stimulation of ODC activity is due to an increased transcription of ODC mRNA. Pretreatment with actinomycin D (2 mg/kg body weight, intraperitoneally) completely prevented the insulin-induced increase in ODC activity, confirming the requirement for the de novo synthesis of ODC mRNA for the effect. More importantly, intracerebroventricular but not subcutaneous injection of beta-endorphin (1 microgram) markedly diminished the stimulatory effect of insulin on hepatic ODC mRNA accumulation. The time course and magnitude of the inhibition of mRNA accumulation essentially mirrored that of the peptide on ODC activity. On the other hand, contrary to the inhibitory effect of beta-endorphin on basal ODC activity, the peptide did not lower basal ODC mRNA levels when given alone. Taken together, the results from these studies provide evidence for the existence of at least two separate mechanisms through which CNS beta-endorphin might downregulate ODC activity in peripheral organs of rat pups. The peptide can suppress insulin-induced ODC activity in the liver tissue by decreasing the rate of transcription of the ODC gene, whereas the inhibition of basal ODC activity appears to involve posttranscriptional mechanisms.
Bartolome
J V
JV
Department of Pharmacology, Duke University, Durham, NC 27710, USA.
Wang
S
S
Bartolome
M B
MB
D000818:Animals; D005260:Female; D007276:Injections, Intraventricular; D008099:Liver / Q000201:enzymology*; D008297:Male; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic; D001615:beta-Endorphin / Q000378:metabolism*
D001615:beta-Endorphin; D009955:Ornithine Decarboxylase