Apolipoprotein gene expression in the rat is regulated in a tissue-specific manner by thyroid hormone.
We have studied the regulation of rat intestinal and hepatic apolipoprotein gene expression, in vivo, after alterations in thyroid hormone status. When compared to those of chow-fed controls, rates of synthesis of intestinal apoA-I and apoB-48 decreased 60-66% in hypothyroid animals and increased three- to fourfold after triiodothyronine (T3) administration. These changes were not accompanied by changes in mRNA abundance. By contrast, intestinal apoA-IV synthesis rates and mRNA abundance were both unaltered over the range of thyroid hormone manipulations tested. Hepatic apoA-I and apoA-IV synthesis rates decreased by 70-80% in hypothyroid animals, while synthesis rates and mRNA abundance increased coordinately six- to eightfold when hypothyroid rats were made hyperthyroid. Hepatic apoE synthesis rates increased twofold in hypothyroid rats and decreased sevenfold in hyperthyroid animals. ApoE mRNA abundance, however, was comparable in all groups. Hypothyroid animals had reduced synthesis rates of hepatic apoB-100 and apoB-48. After induction of hyperthyroidism, apoB-100 synthesis (studied from 5 to 60 min) was undetectable (less than 0.01%) without further change in apoB-48 synthesis and without alterations in either apoB mRNA abundance or transcript size. Despite undetectable hepatic apoB-100 synthesis rates in hyperthyroid animals, total plasma triglyceride secretion rates (after Triton WR-1339 injection) were normalized compared to a 50% decrease in hypothyroid rats. Taken together, the data provide evidence for tissue-specific, independent regulation of apolipoprotein gene expression in vivo. Furthermore, the data suggest that aspects of hepatic triglyceride assembly and secretion and apolipoprotein gene expression may be coordinately responsive to alterations in thyroid hormone status.
Davidson
N O
NO
Department of Medicine, University of Chicago, IL 60637.
Carlos
R C
RC
Drewek
M J
MJ
Parmer
T G
TG
D000818:Animals; D016632:Apolipoprotein A-I; D001053:Apolipoproteins / Q000096:biosynthesis / Q000235:genetics*; D001054:Apolipoproteins A / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007413:Intestinal Mucosa / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D010949:Plasma / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013963:Thyroid Hormones / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism
D016632:Apolipoprotein A-I; D001053:Apolipoproteins; D001054:Apolipoproteins A; D012333:RNA, Messenger; D013963:Thyroid Hormones; D014280:Triglycerides