M. Massimi et al., Differential expression of apolipoprotein E messenger RNA within the rat liver lobule determined by in situ hybridization, HEPATOLOGY, 29(5), 1999, pp. 1549-1555
Apolipoprotein (Apo) E plays a key role in the metabolism of lipoproteins.
It also modulates immunoregulation, cell growth and differentiation and the
response to nerve injury. The liver is a major site of ApoE synthesis. Mos
t of the circulating ApoE is thought to be of hepatic origin with most synt
hesized in hepatocytes, We showed that total liver ApoE messenger RNA (mRNA
) levels were greater in normal adult female rats than in male and that gen
der-specific patterns of liver ApoE mRNA expression were present by in situ
hybridization. In the male liver, the signal was strongest in the portal a
rea, decreasing toward the central vein with the weakest signal in pericent
ral hepatocytes, resulting in a hepatic lobular gradient of expression. In
female liver, a strong periportal signal also was observed that decreased i
n Zone 2, similar to that in males, but which then increased in pericentral
hepatocytes resulting in a bowl-like distribution in marked contrast with
that of the male. The results suggest that ApoE mRNA level is regulated dif
ferentially in hepatocytes within the liver plate and that the regulation i
s gender-dependent. Further, the results suggest that in males, hepatocytes
in the portal area are the major contributors of ApoE to the plasma and/or
sinusoidal pool, whereas in females, both portal and central area hepatocy
tes play an equal role.