期刊
MOLECULAR ENDOCRINOLOGY
卷 14, 期 11, 页码 1739-1749出版社
OXFORD UNIV PRESS INC
DOI: 10.1210/me.14.11.1739
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资金
- NIDCD NIH HHS [DC-03441] Funding Source: Medline
Thyroid hormone (T-3) influences hepatic cholesterol metabolism, and previous studies have established an important role of this hormone in the regulation of cholesterol 7 alpha -hydroxylase (CYP7A), the rate-limiting enzyme in the synthesis of bile acids. To evaluate the respective contribution of thyroid hormone receptors (TR) alpha1 and beta in this regulation, the responses to 2% dietary cholesterol and T-3 were studied in TR alpha1 and TR beta knockout mice under hypo- and hyperthyroid conditions. Our experiments shaw that the normal stimulation in CYP7A activity and mRNA level by T-3 is lost in TR beta-/- but not in TR alpha1-/- mice, identifying TR beta as the mediator of T-3 action on CYP7A and, consequently, as a major regulator of cholesterol metabolism in vivo. Somewhat unexpectedly, T-3-deficient TR beta-/- mice showed an augmented CYP7A response after challenge with dietary cholesterol, and these animals did not develop hypercholesterolemia to the extent as did wild-type (wt) controls. The latter results lend strong support to the concept that TRs may exert regulatory effects in vivo independent of T-3.
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