scholarly journals Activation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in homogenates of developing rat brain

1979 ◽  
Vol 182 (2) ◽  
pp. 367-370 ◽  
Author(s):  
W A Maltese ◽  
J J Volpe

The specific activity of 3-hydroxy-3-methylglutaryl-CoA reductase increases when homogenates of developing rat brain are incubated at 37 degrees C or kept on ice. This increase is completely blocked by the addition of F- to the homogenization medium and the assay mixture. The capacity for activation of the reductase is greatest during the early postnatal period and declines as brain maturation proceeds. The data suggest that catalytic modification of the reductase may play a role in the regulation of cholesterol synthesis in the developing brain.

1985 ◽  
Vol 5 (8) ◽  
pp. 643-648 ◽  
Author(s):  
Anjana Mazumder ◽  
Kamal Das ◽  
Pranab K. Sarkar

The effect of T3 (triiodothyronine) on the induction of tubulin in hypothyroid developing rat brain has been examined using organ cultures of brains from late fetal, neonatal and postnatalrats. The neonatal brain displayed maximum sensitivity to T3. Hypothyroidism resulted in a 26% decline in the level of tubulin in the neonatal brain as opposed to a 5–15% decline in the fetal or postnatal brain. Exposure of the hypothyroi d neonatal brain to T3 for 2 h in culture led to a 61% rise in the level of tubulin in contrast to a 41% increase seen in the case of normal brain. Total protein synthesis was not significantly affected. The preferential decline of tubulin in the neonatal hypothyroid brain, its enhanced sensitivity to T3 compared to normal brain, and the coincidence of the period of sensitivity to that of brain maturation indicate that the regulation of the level of tubulin by T3 in the developing brain is a natural ontogenic phenomenon.


1980 ◽  
Vol 95 (4) ◽  
pp. 495-499 ◽  
Author(s):  
Kazumasa Ishiguro ◽  
Yukichi Suzuki ◽  
Tamotu Sato

Abstract. Changes of nuclear T3 receptors during brain maturation were studied in normal and hypothyroid rats. In normal rats, the higher receptor concentration present in the neonatal period (0.35 ± 0.04 ng T3/mg DNA) decreased at the age of 14 days (0.25 ± 0.02 ng T3/mg DNA), and remained at this level thereafter to 35 days of age (0.25 ± 0.03 T3/mg DNA). In contrast, hypothyroid rats showed a significantly higher concentration than that found in an age-matched control group at the age of 14 days (0.38 ± 0.07 ng T3/mg DNA), and maintained this level up to 35 days of age (0.37 ± 0.03 T3/mg DNA). The binding affinity was similar in both groups and throughout maturation (mean ± sd in normal groups: 1.9 ± 0.3 × 1010m−1, in hypothyroid groups: 1.7 ± 0.2 × 1010m−1). Plasma T3 concentrations showed changes reciprocal to those in the binding capacity of T3 receptors. These results indicate that nuclear T3 receptors in rat brain mature by the age of 14 days, in association with a decrease in binding capacity, and this process seems to be T3-dependent. The physiological role of the high concentration of T3 receptors observed in neonatal and hypothyroid rat brain during development is at present not clear.


1990 ◽  
Vol 123 (1) ◽  
pp. 95-99 ◽  
Author(s):  
Beatriz Ferreiro ◽  
Rosa Pastor ◽  
Juan Bernal

Abstract. The concentration and occupancy of the thyroid hormone receptor have been measured in rat brain nuclear extracts at the end of the fetal period and during the postnatal period. Receptor occupancy attained maximal values at postnatal day 15 (52% of total receptor binding sites occupied by T3) and correlated with plasma and cytosol total and free T3. The values for these parameters showed greater differences throughout development than did receptor occupancy. From gestational day 21 to postnatal day 15, total T3 increased in plasma from 0.18 to 1 nmol/l and in cytosol from 1 to 7.5 pmol/l. Free T3 increased in plasma from 1.2 to 6 pmol/l and in cytosol from 8 to 59 pmol/l. Nuclear free T3, calculated on the basis of receptor occupancy, and Kd increased in parallel, from 39.8 to 107 pmol/l at the same ages. Values for nuclear free T3 were between 2 and 5 times those in cytosol and between 10 and 40 times those in plasma, suggesting the presence of a small free T3 gradient from plasma to the nucleus. All of the above changes take place during the critical period of oligodendrocyte differentiation and the start of myelin gene expression, suggesting that thyroid hormone influences these important events of brain maturation.


1973 ◽  
Vol 132 (3) ◽  
pp. 653-656 ◽  
Author(s):  
Brendan M. Buckley ◽  
Dermot H. Williamson

The existence of acetoacetyl-CoA synthetase in rat brain cytosol is reported. The coupling of this enzyme with cytosolic acetoacetyl-CoA thiolase can provide acetyl-CoA for lipogenesis and cholesterol synthesis without the need for mitochondrial participation. This new route for acetoacetate utilization may be important in developing brain.


1971 ◽  
Vol 122 (5) ◽  
pp. 751-758 ◽  
Author(s):  
N. L. Banik ◽  
A. N. Davison

1. The effect of inhibition of cholesterol synthesis by a hypocholesterolaemic drug (AY-9944) was studied in rat brain during development. 2. At 2 weeks after administration of AY-9944 to young rats 7-dehydrocholesterol accounted for half the total sterol of myelin and other subcellular components. 3. At 4 weeks after injection of the drug 7-dehydrocholesterol had disappeared whereas the cholesterol content of myelin had increased by an equivalent amount. Our studies show that purified myelin has low 7-dehydrocholesterol reductase activity and suggest that 7-dehydrocholesterol is largely converted into cholesterol outside the myelin sheath. 4. Resultant cholesterol may be re-incorporated into myelin by an exchange process. 5. The metabolism of sterols in developing brain is discussed.


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