Role of thyroid hormone in the expression of apolipoprotein A-IV and C-III genes in rat liver.
The genes coding for apolipoproteins A-I, C-III, and A-IV are closely linked to one another in the rat genome. Thyroid hormone stimulates apoA-I expression in rat liver by an unusual mechanism that enhances the maturation of mRNA. This hormone also increases apoA-IV mRNA abundance by a mechanism not yet studied, and its role in the expression of apoC-III has not been defined but may be of relevance to the metabolism of triglyceride-rich lipoproteins. We therefore measured the transcriptional activity of the apoA-IV and apoC-III genes and the abundance of their nuclear RNA and total cellular mRNA in livers of control rats and rats made hyper- and hypothyroid. After a single receptor-saturating dose of triiodothyronine (3 mg/100 g body weight), apoA-IV gene transcription increased at 20 min and reached a maximum of 260% of control at 6 h. Increases of transcription were reflected in increases of nuclear and total apoA-IV mRNA levels. ApoC-III gene transcription was temporarily increased to 160% at 2 h without changes in the abundance of its nuclear or total mRNA over 24 h. Lower hormone doses (20-500 micrograms/100 g body weight) stimulated apoA-IV mRNA transcription as well, but tended to reduce transcription from the apoC-III gene. Upon chronic administration of thyroid hormone, apoA-IV transcription decreased to 55% and nuclear apoA-IV RNA levels to 87% of control. However, total cellular apoA-IV mRNA levels increased to 279% of control, implying stabilization of mRNA in the cytoplasm. ApoC-III transcription decreased to 28% of control, but abundance of nuclear and total cellular apoC-III mRNA was reduced to a lesser extent. In hypothyroid rats, apoA-IV gene expression was decreased fourfold at the transcriptional level. In contrast, apoC-III gene transcription increased to 178% of control, but the abundance of nuclear and total cellular apoC-III mRNA did not differ from control rats. Thus, thyroid hormone affects the abundance of apoA-IV mRNA by changing its synthesis and its rate of degradation and enhances the efficiency of apoC-III mRNA maturation, thereby blunting the net effect of altered mRNA synthesis on mRNA abundance.
Lin-Lee
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YC
Department of Medicine, Baylor College of Medicine, Houston, TX 77030.
Strobl
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Soyal
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Radosavljevic
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Song
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Gotto
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Patsch
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D000818:Animals; D053305:Apolipoprotein C-III; D001054:Apolipoproteins A / Q000235:genetics*; D001056:Apolipoproteins C / Q000235:genetics*; D001483:Base Sequence; D015152:Blotting, Northern; D015870:Gene Expression / Q000187:drug effects*; D006980:Hyperthyroidism / Q000139:chemically induced / Q000378:metabolism; D007037:Hypothyroidism / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D011441:Propylthiouracil; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic / Q000187:drug effects; D014284:Triiodothyronine / Q000494:pharmacology*
D053305:Apolipoprotein C-III; D001054:Apolipoproteins A; D001056:Apolipoproteins C; D012333:RNA, Messenger; C022205:apolipoprotein A-IV; D014284:Triiodothyronine; D011441:Propylthiouracil