Abstract
Hereditary factors in inbred mouse strains affected the rate of sterol synthesis from acetate and the level of hydroxymethylglutaryl coenzyme A reductase in liver in two ways. During the forenoon, rates of sterol synthesis and levels of HMG-CoA reductase activity were two- to five-fold higher in C57L/J and DBA/2J mice than in mice of strains A/HeJ or SWR/J. Due to an apparent difference in the circadian cycle of the two strains, these differences between C57BL/6J and A/HeJ strains were not as great at 4:30 pm, and in some cases the relative order of the values was reversed at this time. Low doses of dietary cholest-4-en-3-one inhibited sterol synthesis and HMG-CoA reductase in livers of all strains tested, whereas high doses or prolonged feeding of the steroid caused a relatively rapid elevation of both sterol synthesis and enzyme activity to above normal levels in several mouse strains including C57L/J. Sterol synthesis and enzyme activity in strain A/HeJ mice were depressed by dietary cholest-4-en-3-one under all conditions tested except when the steroid was fed at a low level for a prolonged period. LAF1 offspring of the cross C57L/J×A/HeJ responded to dietary cholest-4-en-3-one as did the A/HeJ parental strain. Analysis of the effects of cholest-4-en-3-one upon sterol synthesis in backcross offspring of the mating LAF1/J×C57L/J did not permit precise estimation of the number of genes that determine the difference in response to the dietary steroid but did suggest that the number may be relatively small.
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References
Bobek, P., and Ginter, E. (1966). Metabolism of lipids in rats exposed to heat under conditions of a normal and a high fat-high cholesterol diet. J. Nutr. 89 373.
Boyd, G. S., and Oliver, M. F. (1960). Various effects of thyroxine analogues on the heart and serum cholesterol in the rat. J. Endocrinol. 21 25.
Bruell, J. H., Daroczy, A. F., and Hellerstein, H. K. (1962). Strain and sex differences in serum cholesterol levels in mice. Science 135 1071.
Bucher, N. L. R., Overath, P., and Lynen, F. (1960). β-Hydroxy-β-methylglutaryl coenzyme A reductase, cleavage and condensing enzymes in relation to cholesterol formation in rat liver. Biochim. Biophys. Acta 40 491.
Chai, C. K., Amin, A., and Reineke, E. P. (1957). Thyroidal iodine metabolism in inbred and F1 hybrid mice. Am. J. Physiol. 188 499.
Dayton, S., Dayton, J., Drimmer, F., and Kendall, F. E. (1960). Rates of acetate turnover and lipid synthesis in normal, hypothyroid and hyperthyroid rats. Am. J. Physiol. 199 71.
Fletcher, K., and Myant, N. B. (1958). Influence of the thyroid on the synthesis of cholesterol by liver and skin in vitro. J. Physiol. 144 361.
Gruder, W., Nolte, I., and Wieland, O. (1968). The influence of thyroid hormones on β-hydroxy-β-methylglutaryl coenzyme A reductase of rat liver. European J. Biochem. 4 273.
Harold, F. M., Abraham, M. S., and Chaikoff, I. L. (1956). Metabolism of Δ4-cholestenone-4-C14 in the rat. J. Biol. Chem. 221 435.
Hilz, H., Knappe, J., Ringelmann, E., and Lynen, F. (1958). Methylglutaconase, eine neue Hydratase, die am Stoffwechsel verzweigter Carbonsäuren beteiligt ist. Biochem. Z. 329 476.
Hoag, W. G., Meier, H., Dickie, M., Les, E. P., and Dorey, J. (1966). The effect of nutrition on fertility of inbred DBA/2J mice. Lab. Animal Care 16 228.
Kandutsch, A. A., and Saucier, S. E. (1969). Prevention of cyclic and triton-induced increases in hydroxymethylglutaryl coenzyme A reductase and sterol synthesis by puromycin. J. Biol. Chem. 224 2299.
Linn, T. C. (1967). The effect of cholesterol feeding and fasting upon β-hydroxy-β-methylglutarylcoenzyme A reductase. J. Biol. Chem. 242 990.
Rand, P. G., and Quakenbush, F. W. (1965). Cholesterol levels in the hypercholesterolemic rat. Diurnal variations. J. Nutr. 87 485.
Regen, D., Riepertinger, C., Hamprecht, B., and Lynen, F. (1966). The measurement of β-hydroxy-β-methylglutaryl-Co A reductase in rat liver; effects of fasting and refeeding. Biochem. Z. 346 78.
Rosenfeld, R. S., Zumoff, B., and Hellman, L. (1964). Cholestenone metabolism in man. Arch. Biochem. Biophys. 96 84.
Shefer, S., Milch, S., and Mosbach, E. H. (1964). Biosynthesis of 5α-cholestan-3β-ol in the rabbit and guinea pig. J. Biol. Chem. 239 1731.
Siperstein, M. D., and Fagan, M. (1966). Feedback control of mevalonate synthesis by dietary cholesterol. J. Biol. Chem. 241 602.
Steinberg, D., and Fredrickson, D. S. (1956). Inhibitors of cholesterol biosynthesis and the problem of hypercholesterolemia. Ann. N.Y. Acad. Sci. 64 579.
Steinberg, D., Fredrickson, D. S., and Avigan, J. (1958). Effects of Δ4-cholestenone in animals and man. Proc. Soc. Exptl. Biol. Med. 97 784.
Tomkins, G. M., Sheppard, H., and Chaikoff, I. L. (1953). Cholesterol synthesis by liver. IV. Suppression by steroid administration. J. Biol. Chem. 203 781.
Werbin, H., Chaikoff, I. L., and Phillips, B. P. (1964). Conversion of cholesterol to 5α-cholestan-3β-ol in germfree guinea pigs. Biochemistry 3 1558.
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This paper was presented at a symposium entitled “Genetic Control of Mammalian Metabolism” held at The Jackson Laboratory, Bar Harbor, Maine, June 30–July 2, 1969. The symposium was supported in part by an allocation from NIH General Research Support Grant FR 05545 from the Division of Research Resources to The Jackson Laboratory.
Supported in part by NIH Research Grant CA 02758 and NIH Training Grant Tol CA 05013, both from the National Cancer Institute. Some of this work was presented by R.M.P. in partial fulfillment of the requirement for a M.S. degree.
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Packie, R.M., Kandutsch, A.A. Rates of sterol synthesis and hydroxymethylglutaryl coenzyme a reductase levels, and the effects of cholest-4-en-3-one on these parameters, in the livers of inbred strains of mice. Biochem Genet 4, 203–214 (1970). https://doi.org/10.1007/BF00484031
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DOI: https://doi.org/10.1007/BF00484031