Differential regulation of hepatic apolipoprotein A-I and A-II gene expression by thyroid hormone in rat liver.
Apolipoproteins A-I and A-II (apo A-I, apo A-II) are major protein components of high density lipoproteins. Thyroid hormone has a differential effect on the expression of the apo A-I and apo A-II genes in rat liver. Apo A-I gene expression is stimulated by thyroid hormone, whereas apo A-II mRNA abundance is decreased in chronic hyperthyroidism. To determine the regulatory steps involved in this differential effect of thyroid hormone on hepatic apo A-I and apo A-II gene expression, we studied the effect of short term and chronic hyperthyroidism on apo A-I and apo A-II gene transcription rates, nuclear RNA abundance and total cellular mRNA levels. After a single receptor saturating dose of L-triiodothyronine (T3) apo A-II gene transcription was transiently increased to 164% +/- 13% of basal values (P < 0.05) without affecting nuclear apo A-II RNA abundance. Apo A-I gene transcription, however, increased to 158% +/- 8% of baseline levels (P < 0.05) and remained elevated for at least 24 h. Nuclear and total cellular apo A-I mRNA increased more than expected from the increased transcription rate suggesting nuclear RNA stabilization and/or more efficient processing of the primary transcripts. In chronic hyperthyroidism, total cellular apo A-II mRNA abundance decreased to 62% +/- 18% (P < 0.05) and apo A-II gene transcription and apo A-II nuclear RNA were moderately reduced. By contrast, apo A-I nuclear and total cellular RNA were increased several fold by post-transcriptional mechanisms, whereas apo A-I gene transcription was drastically decreased. We conclude that the apo A-I and apo A-II genes in rat liver respond differently to both acute and chronic hyperthyroidism and that their expression is regulated at transcriptional and posttranscriptional levels.
Strobl
W
W
Department of Pediatrics, Univ. of Vienna, Austria.
Chan
L
L
Patsch
W
W
D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics* / Q000378:metabolism; D016633:Apolipoprotein A-II / Q000235:genetics* / Q000378:metabolism; D002908:Chronic Disease; D005786:Gene Expression Regulation; D006980:Hyperthyroidism / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic; D014284:Triiodothyronine / Q000494:pharmacology / Q000502:physiology*
D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D012333:RNA, Messenger; D014284:Triiodothyronine