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. 1980 Oct;66(4):646–654. doi: 10.1172/JCI109900

Influence of thyroid hormone status on mevalonate metabolism in rats.

K R Feingold, M H Wiley, G MacRae, M D Siperstein
PMCID: PMC371637  PMID: 7419712

Abstract

Mevalonate, an essential intermediate in cholesterol synthesis, is metabolized either to cholesterol or, by the shunt pathway, to CO2. Previous investigations have demonstrated that the kidneys are the chief site of circulating mevalonate metabolism and that sex hormones as well as insulin markedly influence circulating mevalonate metabolism. The present study examined in rats the influence of thyroid hormone status on mevalonate metabolism in vivo and in vitro. L-thyroxine administration increased renal conversion of circulating mevalonate to cholesterol, 41% in the females and 22% in the males. Conversely, hypothyroidism induced by 6 N propyl-2-thiouracil reduced renal conversion of circulatng mevalonate to cholesterol by 45% in females and 27% in males; thyroid hormone replacement in these animals returned cholesterogenesis in the kidneys to supranormal levels. Neither L-thyroxine nor hypothyroidism altered circulating mevalonate conversion to cholesterol in the liver or carcass. In vitro studies confirmed the in vivo observations. Changes in thyroid hormone produced only minor changes in the shunt pathway of mevalonate metabolism. This study demonstrates that the major effect of the thyroid hormone on the metabolism of circulating mevalonate is to alter the conversion of mevalonate to cholesterol, an effect localized solely to the kidneys.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BYERS S. O., ROSENMAN R. H., FRIEDMAN M., BIGGS M. W. Rate of cholesterol synthesis in hypo- and hyperthyroid rats. J Exp Med. 1952 Nov;96(5):513–516. doi: 10.1084/jem.96.5.513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Edmond J., Popják G. Transfer of carbon atoms from mevalonate to n-fatty acids. J Biol Chem. 1974 Jan 10;249(1):66–71. [PubMed] [Google Scholar]
  3. FLETCHER K., MYANT N. B. Influence of the thyroid on the synthesis of cholesterol by liver and skin in vitro. J Physiol. 1958 Dec 4;144(2):361–372. doi: 10.1113/jphysiol.1958.sp006107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Hellstrom K. H., Siperstein M. D., Bricker L. A., Luby L. J. Studies of the in vivo metabolism of mevalonic acid in the normal rat. J Clin Invest. 1973 Jun;52(6):1303–1313. doi: 10.1172/JCI107301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. KRITCHEVSKY D. Influence of thyroid hormones and related compounds on cholesterol biosynthesis and degradation: a review. Metabolism. 1960 Nov;9:984–994. [PubMed] [Google Scholar]
  6. Linder J. R., Beitz D. C. Sterol synthesis and CO2 production from mevalonate in calves. J Lipid Res. 1978 Sep;19(7):836–840. [PubMed] [Google Scholar]
  7. Ness G. C., Dugan R. E., Lakshmanan M. R., Nepokroeff C. M., Porter J. W. Stimulation of hepatic beta-hydroxy-beta-methylglutaryl coenzyme A reductase activity in hypophysectomized rats by L-triiodothyronine. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3839–3842. doi: 10.1073/pnas.70.12.3839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Popják G., Boehm G., Parker T. S., Edmond J., Edwards P. A., Fogelman A. M. Determination of mevalonate in blood plasma in man and rat. Mevalonate "tolerance" tests in man. J Lipid Res. 1979 Aug;20(6):716–728. [PubMed] [Google Scholar]
  9. Raskin P., Siperstein M. D. Mevalonate metabolism by renal tissue in vitro. J Lipid Res. 1974 Jan;15(1):20–25. [PubMed] [Google Scholar]
  10. Righetti M., Wiley M. H., Murrill P. A., Siperstein M. D. The in vitro metabolism of mevalonate by sterol and non-sterol pathways. J Biol Chem. 1976 May 10;251(9):2716–2721. [PubMed] [Google Scholar]
  11. Siperstein M. D., Fagan V. M. Feedback control of mevalonate synthesis by dietary cholesterol. J Biol Chem. 1966 Feb 10;241(3):602–609. [PubMed] [Google Scholar]
  12. Wiley M. H., Howton M. M., Siperstein M. D. Sex differences in the sterol and nonsterol metabolism of mevalonate. J Biol Chem. 1979 Feb 10;254(3):837–842. [PubMed] [Google Scholar]
  13. Wiley M. H., Howton M. M., Siperstein M. D. The quantitative role of the kidneys in the in vivo metabolism of mevalonate. J Biol Chem. 1977 Jan 25;252(2):548–554. [PubMed] [Google Scholar]

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