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Endocrine and Metabolism Unit, University of Southampton School of Medicine, Southampton General Hospital, Southampton SO16 6YD, United Kingdom
Increased plasma fibrinogen concentrations are a
recognized risk factor for coronary heart disease, and increased
fibrinogen levels in adults are associated with parameters of reduced
early growth. We studied fibrinogen gene expression in adult offspring of dams fed either a 20% (control) or an 8% protein diet
[maternal low-protein (MLP) rats] during pregnancy and
lactation and determined whether any effects were consistent between
left and right liver lobes, since the fetal liver has a unique blood
supply that produces differential stimuli to the left and right lobes.
In MLP offspring, there was a reduction in all three fibrinogen mRNA
copy numbers in the left liver lobe [left vs. right lobes for
-,
-, and
-fibrinogen (×106 copies/ng total
RNA): 8.04 vs. 23.16, P < 0.001; 4.74 vs. 13.07, P
< 0.001; and 4.61 vs. 16.38, P = 0.007, respectively], with a parallel reduction in fibrinogen
concentration in the left liver lobe (8.53 ± 0.33 vs. 10.41 ± 0.65 arbitrary units, P = 0.014, left and right lobes,
respectively). No such effect was observed in offspring of control
dams. To investigate the underlying mechanism, glucocorticoid receptor
function and mRNA levels were studied, since expression of fibrinogen
genes is regulated by glucocorticoid hormones. The binding affinity of
the high-affinity glucocorticoid receptor was reduced only in the left
liver lobe of the MLP offspring (P = 0.02, left. vs. right),
with a parallel reduction in this lobe in glucocorticoid receptor mRNA
level (P = 0.006, left vs. right). In conclusion, maternal
dietary protein restriction reduces fibrinogen gene expression,
fibrinogen protein, and mRNA level and binding affinity of
glucocorticoid receptors only in the left liver lobe of the adult offspring.
low protein; liver; mRNA; glucocorticoids
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