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By Rodolfo Paoletti, Dr. David Kritchevsky

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R O D W E L L E T A L . —■ —. - . / ■ £ N 240 S 200 g; 160 ^ 120 $ 80 * — 40 ^ fPÄRtTNESSN^^SS 28 20 ■ 12 4 I L _L 1 I, ILiI 0 8 0 0 1200 1600 2000 2400 0 4 0 0 TIME OF DAY F I G . 10. HMG-CoA reductase activity and incorporation of [ 3 H]leucine into purified reductase. Reproduced, with permission, from Higgins et al. (1971). , 1969; Shapiro and Rodwell, 1969; Kandutsch and Saucier, 1969). Rapid turnover of reductase protein was soon confirmed by more definitive techniques. , 1971) (Fig. 10) and material precipitated by antibody to purified reductase (Higgins and Rudney, 1973) rise and fall roughly in phase with the diurnal variation in reductase activity.

Elucidation of the factors responsible for these variable properties may yield insight into the nature of the enzyme in situ. VI. Diurnal Rhythm of Mammalian Liver HMG-CoA Reductase A. G E N E R A L DESCRIPTION The observations summarized here are restricted to rodents, and for the most part, to rats. , 1972), and certain rat and mouse hepatomas (Goldfarb and Pitot, 1971). It has b e e n repeatedly demonstrated in many laboratories. However, the existence of rhythmic variations in reductase activity in other species, particularly in humans, or in other tissues has not yet b e e n established.

R O D W E L L E T AL. 3 Inhibition of diurnal rise (%) 0 52 71 90 a From Nepokroeff et al. (1974). Glucagon (2 /ng/gm body weight) or hydrocortisone (25 /u,g/gm body weight) were administered subcutaneously to normal rats at 1400 hours and again at 1800 hours. Dibutyryl cyclic AMP (50 />tg/gm body weight) was given intraperitoneally at 1400 hours and again at 1800 hours. , 1973). , glucocorticoids) may, however, be responsible for control of the diurnal rhythm. Since diurnal rhythm studies have not as yet b e e n reported for rats deficient solely in thyroid hormone, their precise role cannot at present be deduced.

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