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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1973 Dec;70(12 Pt 1-2):3839–3842. doi: 10.1073/pnas.70.12.3839

Stimulation of Hepatic β-Hydroxy-β-methylglutaryl Coenzyme A Reductase Activity in Hypophysectomized Rats by L-Triiodothyronine

Gene C Ness 1,2, Richard E Dugan 1,2, M R Lakshmanan 1,2, Carl M Nepokroeff 1,2, John W Porter 1,2
PMCID: PMC427340  PMID: 4521209

Abstract

Diurnally varying activity of hepatic β-hydroxy-β-methylglutaryl coenzyme A reductase (EC 1.1.1.34) was decreased to very low levels in hypophysectomized rats with no discernable diurnal rhythm retained. Administration of triiodothyronine (100 μg/100 g of body weight) produced a supranormal level of reductase activity, about 3-4 times the highest activity found in normal rats. Reductase activity began to rise about 30 hr after hormone administration, maintained a constant high level from 48 to 72 hr, and declined to the control level by 96 hr. The supranormal response was elicited equally well either during the day or at night. When normal animals received triiodothyronine, reductase activity was increased only to a level comparable to the highest level found in normal rats. Administration of hydrocortisone markedly inhibited the triiodothyronine-induced increase in reductase activity. This finding suggests that glucocorticoids might act to suppress and thus account for the smaller increase in reductase activity observed in normal rats given triiodothyronine. When actinomycin D was given before the triiodothyronine-induced rise in reductase activity, the increase was effectively blocked, indicating that the hormonal effect requires new RNA synthesis.

Keywords: hydrocortisone, RNA synthesis, cholesterol biosynthesis

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Selected References

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

  1. BUCHER N. L., OVERATH P., LYNEN F. beta-Hydroxy-beta-methyl-glutaryl coenzyme A reductase, cleavage and condensing enzymes in relation to cholesterol formation in rat liver. Biochim Biophys Acta. 1960 Jun 3;40:491–501. doi: 10.1016/0006-3002(60)91390-1. [DOI] [PubMed] [Google Scholar]
  2. Bortz W. M. Noradrenalin-induced increase in hepatic cholesterol synthesis and its blockade by puromycin. Biochim Biophys Acta. 1968 May 1;152(3):619–626. doi: 10.1016/0005-2760(68)90102-1. [DOI] [PubMed] [Google Scholar]
  3. Brown M. R., Hedge G. A. Multiple effects of glucocorticoids on TSH secretion in unanesthetized rats. Endocrinology. 1973 May;92(5):1305–1311. doi: 10.1210/endo-92-5-1305. [DOI] [PubMed] [Google Scholar]
  4. De Matteis F. Stimulation of liver cholesterol synthesis by actinomycin D. Biochem J. 1968 Oct;109(5):775–785. doi: 10.1042/bj1090775. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dugan R. E., Slakey L. L., Briedis A. V., Porter J. W. Factors affecting the diurnal variation in the level of -hydroxy- -methylglutaryl coenzyme A reductase and cholesterol-synthesizing activity in rat liver. Arch Biochem Biophys. 1972 Sep;152(1):21–27. doi: 10.1016/0003-9861(72)90188-9. [DOI] [PubMed] [Google Scholar]
  6. Edwards P. A. Effect of adrenalectomy and hypophysectomy on the circadian rhythm of -hydroxy- -methylglutaryl coenzyme A reductase activity in rat liver. J Biol Chem. 1973 Apr 25;248(8):2912–2917. [PubMed] [Google Scholar]
  7. FLETCHER K., MYANT N. B. Effects of thyroxine on the synthesis of cholesterol and fatty acids by cell-free fractions of rat liver. J Physiol. 1960 Nov;154:145–152. doi: 10.1113/jphysiol.1960.sp006569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Goldfarb S., Pitot H. C. Improved assay of 3-hydroxy-3-methylglutaryl coenzyme A reductase. J Lipid Res. 1971 Jul;12(4):512–515. [PubMed] [Google Scholar]
  9. Goldfarb S., Pitot H. C. Stimulatory effect of dietary lipid and cholestyramine on hepatic HMG CoA reductase. J Lipid Res. 1972 Nov;13(6):797–801. [PubMed] [Google Scholar]
  10. Guder W., Nolte I., Wieland O. The influence of thyroid hormones on beta-hydroxy-beta-methylglutaryl-coenzyme A reductase of rat liver. Eur J Biochem. 1968 Apr 3;4(2):273–278. doi: 10.1111/j.1432-1033.1968.tb00204.x. [DOI] [PubMed] [Google Scholar]
  11. HILZ H., KNAPPE J., RINGELMANN E., LYNEN F. Methylglutaconase, eine neue Hydratase, die am Stoffwechsel verzweigter Carbonsäuren beteiligt ist. Biochem Z. 1958;329(6):476–489. [PubMed] [Google Scholar]
  12. HUFF J. W., GILFILLAN J. L., HUNT V. M. EFFECT OF CHOLESTYRAMINE, A BILE ACID-BINDING POLYMER ON PLASMA CHOLESTEROL AND FECAL BILE ACID EXCRETION IN THE RAT. Proc Soc Exp Biol Med. 1963 Nov;114:352–355. doi: 10.3181/00379727-114-28674. [DOI] [PubMed] [Google Scholar]
  13. Hamprecht B., Nüssler C., Lynen F. Rhythmic changes of hydroxymethylglutaryl coenzyme a reductase activity in livers of fed and fasted rats. FEBS Lett. 1969 Jul;4(2):117–121. doi: 10.1016/0014-5793(69)80210-3. [DOI] [PubMed] [Google Scholar]
  14. Higgins M., Kawachi T., Rudney H. The mechanism of the diurnal variation of hepatic HMG-CoA reductase activity in the rat. Biochem Biophys Res Commun. 1971 Oct 1;45(1):138–144. doi: 10.1016/0006-291x(71)90061-1. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Kandutsch A. A., Saucier S. E. Prevention of cyclic and triton-induced increases in hydroxymethylglutaryl coenzyme A reductase and sterol synthesis by puromycin. J Biol Chem. 1969 May 10;244(9):2299–2305. [PubMed] [Google Scholar]
  17. Lakshmanan M. R., Nepokroeff C. M., Ness G. C., Dugan R. E., Porter J. W. Stimulation by insulin of rat liver -hydroxy- -methylglutaryl coenzyme A reductase and cholesterol-synthesizing activities. Biochem Biophys Res Commun. 1973 Feb 5;50(3):704–710. doi: 10.1016/0006-291x(73)91301-6. [DOI] [PubMed] [Google Scholar]
  18. Lakshmanan M. R., Phillips W. E., Brien R. L. Effect of p-chlorophenoxyisobutyrate (CPIB) fed to rats on hepatic biosynthesis and catabolism of ubiquinone. J Lipid Res. 1968 May;9(3):353–356. [PubMed] [Google Scholar]
  19. Shapiro D. J., Imblum R. L., Rodwell V. W. Thin-layer chromatographic assay for HMG-CoA reductase and mevalonic acid. Anal Biochem. 1969 Oct 1;31(1):383–390. doi: 10.1016/0003-2697(69)90279-6. [DOI] [PubMed] [Google Scholar]
  20. Shapiro D. J., Rodwell V. W. Diurnal variation and cholesterol regulation of hepatic HMG-CoA reductase activity. Biochem Biophys Res Commun. 1969 Nov 20;37(5):867–872. doi: 10.1016/0006-291x(69)90972-3. [DOI] [PubMed] [Google Scholar]
  21. Shapiro D. J., Rodwell V. W. Regulation of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase and cholesterol synthesis. J Biol Chem. 1971 May 25;246(10):3210–3216. [PubMed] [Google Scholar]
  22. 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]
  23. Slakey L. L., Craig M. C., Beytia E., Briedis A., Feldbruegge D. H., Dugan R. E., Qureshi A. A., Subbarayan C., Porter J. W. The effects of fasting, refeeding, and time of day on the levels of enzymes effecting the conversion of -hydroxy- -methylglutaryl-coenzyme A to squalene. J Biol Chem. 1972 May 25;247(10):3014–3022. [PubMed] [Google Scholar]
  24. TOMKINS G. M., CHAIKOFF I. L., BENNETT L. L. Cholesterol synthesis by liver. II. Effect of hypophysectomy. J Biol Chem. 1952 Dec;199(2):543–545. [PubMed] [Google Scholar]

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