Precocious induction of tyrosine aminotransferase mRNA by hydrocortisone in cultured fetal rat hepatocytes at different developmental stages

Hoffmann, Birgit; Paul, Dieter

doi:10.1002/jcp.1041430220

Cited by 9 publications

(4 citation statements)

References 31 publications

(26 reference statements)

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“…Appropriate controls showed that in cultured normal fetal hepatocytes the TAT and the MT-I genes gained the competence for glucocorticoid induction (Figure 3b), thus resembling the situation in newborn animals. This indicates that the defined culture conditions used here supported the maintenance and the 'maturation' of the hepatocyte phenotype (Hoffmann and Paul, 1990) mRNA levels of genes expressed in livers of newborn normal (cfh) and homozygous deletion mutant (C14C6S) mice. The experiments were carried out as described in Materials and methods.…”

Section: Resultsmentioning

confidence: 63%

“…Transcription in normal and c 14CoS fetal hepatocytes in primary culture Previous studies had indicated that fetal hepatocytes in primary culture undergo differentiation and 'maturation' leading to precocious induction of the TAT gene in response to hydrocortisone (Hoffmann and Paul, 1990;Shelly et al, 1989). Therefore we examined the transcriptional patterns of cultured primary fetal hepatocytes from normal and cJ4CoS mice.…”

Section: Resultsmentioning

confidence: 99%

“…Previous work had shown that fetal liver cells, when placed into primary culture, undergo 'maturation' and become precociously susceptible to the positive regulatory effects of glucocorticoids (Hoffmann and Paul, 1990). Such maturation processes occurring in culture may be the consequence of the disintegration of the three-dimensional architecture of liver tissue (Clayton et al, 1985).…”

Section: Discussionmentioning

confidence: 99%

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Transcriptional control in hepatocytes of normal and c14CoS albino deletion mice.

Tönjes¹,

Xanthopoulos²,

Darnell³

et al. 1992

The EMBO Journal

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The transcription rates of the albumin and alpha‐fetoprotein (alpha FP) genes were reduced to marginally detectable levels in livers of newborn or fetal c14CoS albino deletion mutant mice, which lack the hepatocyte specific developmental regulation (hsdr‐1) locus on chromosome 7 and die shortly after birth. However, steady‐state levels of these two mRNAs in livers of mutant mice were similar to those in normal mice, where these genes are actively transcribed. In c14CoS mice, transcription rates of transcription factor genes HNF‐1, C/EBP and HNF‐4 were reduced, albeit to different extents. These effects are specific because transcription of the HNF‐3, DBP, LAP and Jun‐B genes remained normal in mutant mice. Steady‐state levels of all of these mRNAs reflected the transcriptional activities. Levels of HNF‐1 and HNF‐4 mRNAs showed much greater depression than that of C/EBP in mutant liver. The availability of this group of transcription factors may be reduced in c14CoS hepatocytes and therefore caused depressed transcription rates of their target genes such as those encoding albumin and alpha FP. However, the normal steady‐state levels of albumin and alpha FP mRNAs in mutant mice remains unexplained. Fetal c14CoS hepatocytes in primary culture did acquire competence for glucocorticoid inducible transcription of the albumin, alpha FP, HNF‐4 and metallothionein genes but not of the tyrosine aminotransferase (TAT) gene. These results indicate that the hsdr‐1 locus is dispensable for the glucocorticoid induced transcription of these genes but not of TAT. The effects caused by the c14CoS deletion are pleiotropic in controlling the expression of numerous genes at distinct levels in the liver.

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Section: Resultsmentioning

confidence: 63%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Transcriptional control in hepatocytes of normal and c14CoS albino deletion mice.

Tönjes¹,

Xanthopoulos²,

Darnell³

et al. 1992

The EMBO Journal

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“…The fetal rat hepatocytes proliferate in primary culture in response to epidermal growth factor (EGF) and insulin, 1-3 whereas dexamethasone or hydrocortisone and glucagon have been implicated in the regulation of the maturation of these rat hepatocytes. [4][5][6] GGTase (E.C.2.3.2.2), a membrane-bound enzyme indirectly involved in transport of aminoacids and peptides across the membrane, [7][8] was found to be significantly high in rat fetal livers and low in adults. [9][10][11] In vivo, GGTase activity was shown to increase during proliferation of hepatocytes after D-galactosamine injury.…”

Section: Introductionmentioning

confidence: 99%

Tyrosine aminotransferase and gamma‐glutamyl transferase activity in human fetal hepatocyte primary cultures under proliferative conditions

Rehman¹,

Qamar

Khan³

et al. 2003

Cell Biochemistry & Function

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The ontogeny of gamma-glutamyl transferase (GGTase; E.C.2.3.2.2) and tyrosine aminotransferase (TAT; E.C.2.6.1.5) activities in 14 to 36 weeks gestational and neonatal hepatocytes during development of human fetal liver was studied. Subsequently, 20-24 weeks gestational hepatocytes were cultured in media supplemented with epidermal growth factor (EGF) and insulin with or without glucagon and dexamethasone to investigate the proliferation and differentiation of fetal hepatocyte in vitro using GGTase and TAT as biochemical markers. During the development of the liver, the activity of GGTase increased continuously from the first trimester through the third trimester and decreased (p < 0.001) in neonates. A low basal level of TAT activity was seen only during the third trimester, which then increased significantly (p < 0.001) in neonates. Fetal hepatocytes, in the presence of EGF and insulin, undergo proliferation from the fourth to 10th day with an increase in cell number (p < 0.001) and concomitant increase (p < 0.001) in GGTase activity. As the cells attain confluence, enzyme activity decreased significantly (p < 0.001) from the 10th to 16th day. Maximal TAT activity (p < 0.001) was observed at 48 h of culture, which decreased, but not significantly, during cell proliferation and the enzyme activity was regained as the cultures attained confluence. Furthermore, TAT activity was induced synergistically (p<0.001) in the presence of glucagon and dexamethasone, while GGTase was inhibited (p<0.001). These results indicate that GGTase increases with proliferation, whereas TAT, once it has been expressed, is not suppressed during cell proliferation. In conclusion, human fetal hepatocytes undergo enzymic differentiation by 48 h of culture, and proliferate with an increase in GGTase in the presence of growth factors with maintenance of differentiated status up to the studied 16 days of culture.

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Regulation of albumin expression in fetal rat hepatocytes cultured under proliferative conditions: Role of epidermal growth factor and hormones

Juan¹,

Benito²,

Fabregat³

1992

Journal Cellular Physiology

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Sustained production of plasma proteins, notably albumin, is a reliable indicator of the differentiated state of hepatocytes. In this work, we have developed a fetal hepatocyte culture system where studying the regulation of albumin expression in proliferating liver cells. Our results show that under proliferative conditions (i.e., in the presence of EGF) fetal hepatocytes maintain albumin production above control quiescent non-treated cells. Glucagon and noradrenaline have no effect on the proliferation induced by EGF in cultured fetal hepatocytes; however, they act synergistically with the growth factor, increasing intracellular albumin levels. The maximum response is obtained by treatment of cells with EGF and noradrenaline. The stimulatory noradrenergic effect is mimicked by agents that increase cyclic AMP levels (forskolin plus IBMX). However, vasopressin or phorbol esters have no effect on albumin production, neither alone nor in combination with EGF. Dexamethasone, which does not alter the proliferative induction of EGF, increases albumin content. This effect is independent of the proliferative status of the cells and is not enhanced by glucagon, noradrenaline, or cyclic AMP increasing agents. The hormonal changes observed in albumin production partially correlate with changes in mRNA levels. This is the first time that cyclic AMP increasing agents are shown to act synergistically with EGF, increasing the expression of this liver specific gene.

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Precocious induction of tyrosine aminotransferase mRNA by hydrocortisone in cultured fetal rat hepatocytes at different developmental stages

Cited by 9 publications

References 31 publications

Transcriptional control in hepatocytes of normal and c14CoS albino deletion mice.

Transcriptional control in hepatocytes of normal and c14CoS albino deletion mice.

Tyrosine aminotransferase and gamma‐glutamyl transferase activity in human fetal hepatocyte primary cultures under proliferative conditions

Regulation of albumin expression in fetal rat hepatocytes cultured under proliferative conditions: Role of epidermal growth factor and hormones

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