Cytochrome p-450 gene expression in the functional units of the fetal liver

Abstract

Hepatocytes of the right and left lobes of the fetal liver are surrounded by different microenvironments. The right and left lobes of the fetal liver are perfused by vascular systems carrying different concentrations of oxygen and constitute distinct functional units. The aim of this study was to assess the expression of the phenobarbital-inducible cytochrome P-450 b,e genes in hepatocytes of the right and left fetal liver lobes in mice. Northern-blot analysis using [32P]cDNAs and quantitative dot-blot hybridization were performed to assess the size and levels of these mRNAs in the right and left fetal liver lobes. In fetal mice, the levels of cytochrome P-450, b,e mRNAs were higher in the left than in the right fetal liver lobe. During the last days of gestation and in the immediate postnatal period, the levels of liver cytochrome P-450 b,e mRNAs increased predominantly in the left liver lobe. In contrast, the levels of albumin and alpha-fetoprotein mRNAs (genes studied to assess the specificity of these findings) were similar in each of functional units of the fetal liver. Phenobarbital induction of cytochromes P-450 b,e mRNAs was not observed in either of the fetal liver lobes. Postnatally, phenobarbital induced these cytochromes similarly in the right and left liver lobes. Therefore, the microenvironment surrounding fetal hepatocytes seems to influence the expression of the cytochrome P-450 b,e genes. This lobar heterogeneity of expression disappears as the pattern of adult liver circulation is attained.

Ontogeny of CYP3A and P‐Glycoprotein in the Liver and the Small Intestine of the Göttingen Minipig: An Immunohistochemical Evaluation

“…In foetal sheep, monkey and mouse livers, a higher CYP content was reported for the left lobe in comparison with the right lobe. A higher oxygenation due to more extensive vascularization of the foetal left liver lobe is thought to be the reason for this observation [28][29][30]. However, this conclusion could not be drawn from our results.…”

“…For the evaluation of the CYP3A4‐ and CYP3A7 homologues in the liver, intensity of staining was evaluated with a score ranging from 0 to 5. As differences in blood perfusion and CYP content have been described between right and left foetal liver lobes in several species both were evaluated separately in the minipig foetuses.…”

Demonstration by in situ hybridization of the zonal modulation of rat liver cytochrome P-450b and P-450e gene expression after phenobarbital.

“…5 A shows that only PB induced these mRNA. Maximal induction with PB was attained by [16][17][18][19][20][21][22][23][24] h, as was previously…”

“…In some experiments, poly (At) RNA was isolated from total RNA using poly (U) paper (Hybond -m AP paper; Amersham Corp., Chicago, IL). The levels ofcytochromes P-450b,e mRNA afterpOHPB administration were measured by quantitative dot blot hybridization (14,21). A Minifold II system and nitrocellulose filters were used.…”

Effects of interleukin-1β and indomethacin on expression of interleukin-1β gene in brain hemispheres

“…The results of hybridization were quantitatively analyzed on an Ultroscan-XL laser densitometer (LKB). The data from different filters were standardized using internal controls [4]. The results were statistically processed using the nonparametric Wilcoxon--Mann--Whitney test.…”