THYROID-HORMONE RAPIDLY INCREASES CHOLESTEROL 7-ALPHA-HYDROXYLASE MESSENGER-RNA LEVELS IN HYPOPHYSECTOMIZED RATS
THYROID-HORMONE RAPIDLY INCREASES CHOLESTEROL 7-ALPHA-HYDROXYLASE MESSENGER-RNA LEVELS IN HYPOPHYSECTOMIZED RATS
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DOI：
10.1016/0005-2760(94)90068-x
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发表时间：
1994-10-06
期刊：
影响因子：
--
通讯作者：
ZHAO, ZH
中科院分区：
文献类型：
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作者：
NESS, GC;PENDLETON, LC;ZHAO, ZH
本文研究了三碘甲腺原氨酸对去垂体大鼠肝脏胆固醇7α-羟基酶mRNA的诱导作用。与正常对照组相比，这些大鼠的胆固醇7α-羟基酶mRNA水平显著降低。在给予三碘甲腺原氨酸后30分钟内，可检测到该基因的表达增加。当三碘甲腺原氨酸的剂量为每100克体重0.25微克时，肝细胞核甲状腺激素受体的占有率为50%，导致羟基酶mRNA水平显著增加。胆固醇7α-羟基酶的半衰期约为30min，不受甲状腺激素的影响。在三碘甲腺原氨酸引起超诱导后，给予蛋白质合成抑制剂放线菌酮。肝脏HMG-CoA还原酶mRNA水平在这些研究中检测的2小时内不受这些激素剂量的影响，而去垂体大鼠肝脏中的HMG-CoA还原酶基因水平也很低。结果提示，甲状腺激素可能对肝脏胆固醇7α-羟基酶基因的表达起主要作用。这在一定程度上可以解释甲状腺激素的降胆固醇作用。
The induction of hepatic cholesterol 7 alpha-hydroxylase mRNA by triiodothyronine was investigated in hypophysectomized rats. These rats exhibited markedly decreased levels of cholesterol 7 alpha-hydroxylase mRNA compared to normal controls. An increase in this mRNA could be detected within 30 min after giving triiodothyronine. A triiodothyronine dose of 0.25 mu g per 100 g of body weight, which produces 50% occupancy of hepatic nuclear thyroid hormone receptors, caused significant increases in hydroxylase mRNA levels. The half-life of cholesterol 7 alpha-hydroxylase mRNA was about 30 min and was not affected by thyroid hormone. Administration of the protein synthesis inhibitor, cycloheximide, after triiodothyronine caused superinduction. Hepatic HMG-CoA reductase mRNA levels, which are also low in livers from hypophysectomized rats, were unaffected by these doses of hormone within the 2 h time-frame examined in these studies. The results suggest that thyroid hormone may exert a primary affect on the expression of the hepatic cholesterol 7 alpha-hydroxylase gene. This could explain, in part, the hypocholesterolemic effect of thyroid hormone.