Insulin inhibits the glucocorticoid‐mediated increase in hepatocyte EGF binding

Lin, Qixiong; Blaisdell, Joyce; O’Keefe, Edward J.; Earp, H. Shelton

doi:10.1002/jcp.1041190304

Cited by 41 publications

(22 citation statements)

References 30 publications

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“…Our results extend the earlier observation of Lin et al (1984) of a 10-25% decrease in hepatocyte EGF binding between 24 and 48 h r in culture and parallel those of Fishman et al (19851, Dunn and Hubbard (1984) of 300,000 sites per cell in homogenates of freshly isolated liver. The ability of EGF to induce receptor down-regulation appeared to wane with time in culture and may result from the striking decrease in liver specific gene transcription that was detected by Clayton and Darnell (1983) in cultured mouse hepatocytes in the first 24 hr after plating.…”

Section: Discussionsupporting

confidence: 94%

Transforming growth factor beta (TGF‐β) inhibits hepatocyte DNA synthesis independently of EGF binding and egf receptor autophosphorylation

Russell

1988

Journal Cellular Physiology

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Subpicomolar concentrations of human platelet-derived transforming growth factor beta (TGF-beta) inhibited growth factor-stimulated DNA synthesis in primary cultures of adult rat hepatocytes. This inhibition was not the result of changes in the size of intracellular pools of 3H-thymidine and was not dependent on the state of confluence of the cells. A 24-hr exposure to TGF-beta either before or after insulin/EGF stimulation was as inhibitory on DNA synthesis between 48 and 72 hr of culture as was TGF-beta present throughout 72 hr of culture. From 12 hr in culture to 24 hr, hepatocyte EGF binding sites dropped from about 230,000 to 85,000 per cell with no significant change in Kd, but with a loss in capacity for EGF-induced receptor down-regulation. Maximally inhibitory concentrations of TGF-beta did not compete with EGF for the EGF receptor, and a 4- to 24-hr exposure to TGF-beta did not alter subsequent EGF binding. Coincubation of hepatocytes with TGF-beta and EGF did not influence the 60% reduction in EGF binding sites produced by EGF alone. In addition, TGF-beta did not prevent EGF-induced autophosphorylation of the 170,000 dalton EGF receptor in membranes from whole liver. Our studies suggest that TGF-beta regulates hepatocyte growth independently of changes in EGF receptor number, ligand affinity, or postbinding autophosphorylation.

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Section: Discussionsupporting

confidence: 94%

Transforming growth factor beta (TGF‐β) inhibits hepatocyte DNA synthesis independently of EGF binding and egf receptor autophosphorylation

Russell

1988

Journal Cellular Physiology

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“…This clearly indicated a time-dependent effect on c-fos mRNA expression by the glucocorticoid. This is consistent with its proposed time-dependent mechanism of increasing EGF binding (Lin et al 1984), induction of estrogen receptor mRNA (Ulisse et al 1994) or stabilization of a broad range of mRNAs in hepatocytes (Reid et al 1986). …”

Section: Discussionsupporting

confidence: 84%

Differential expression of c-fos and c-myc protooncogenes by estrogens, xenobiotics and other growth-stimulatory agents in primary rat hepatocytes

Lee

Edwards

2003

Arch Toxicol

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Mechanism(s) of tumour promotion in liver by estrogens and other xenobiotics such as alpha-hexachlorocyclohexane (HCH), 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT) and phenobarbital (PB), are not well understood although it is clear that growth stimulation is one important element in their action. To help in characterizing mechanisms of growth control by these compounds, their effects on the expression of immediate-early protooncogenes c- fos and c- myc have been examined and compared with other compounds that stimulate DNA synthesis in primary cultures of normal rat hepatocytes. Expression of c- fos was undetectable in cultures not exposed to growth factors. Although neither epidermal growth factor (EGF) nor 17beta-estradiol (E(2)) alone had marked effects on c- fos mRNA, the two acted synergistically to cause clear c- fos expression, maximal 1-2 h after growth factor addition and when test agents were added on the first day in culture. Neither insulin nor dexamethasone alone induced c- fos mRNA but stimulation of c- fos expression by EGF plus estradiol occurred earlier in the presence of insulin, and was augmented by preincubation of cells with dexamethasone. EGF + E(2)-induced c- fos mRNA was completely abolished by actinomycin D, suggesting that transcription is the major mechanism for c- fos induction by E(2) + EGF. Compounds that strongly stimulate hepatocyte DNA synthesis such as norepinephrine, pyruvate, prolactin, glutethimide, monensin, ammonium chloride, and normal rat serum when in combination with EGF, all failed (when added with EGF) to affect c- fos mRNA expression. Thus, induction of c- fos expression may be a component of estradiol's growth stimulatory effect in cultured hepatocytes but this is not the case for other compounds that strongly stimulate DNA synthesis. Unlike c- fos mRNA, c- myc mRNA was detectable in hepatocyte cultures without added growth factor, was augmented within 2 h of exposure to EGF, and was further increased by adding E(2), other estrogens or a variety of other stimulators of DNA synthesis in hepatocytes. This suggests that increased c- myc expression may be a common effect of many of these agents in combination with EGF.

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“…A loss of EGF receptor binding over time in untreated primary hepatocyte cultures has been reported by Lin et al (1984). We also found a reduction in specific 1251-EGF binding during the first 24 hr in culture, reaching 51% 12% of that seen at the beginning of the assay (0 hr;P = 0.05, n =6).…”

Section: Interaction Of Ne and Egfsupporting

confidence: 62%

Norepinephrine and epidermal growth factor: Dynamics of their interaction in the stimulation of hepatocyte DNA synthesis

Cruise

Michalopoulos

1985

Journal Cellular Physiology

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Primary cultures of adult rat hepatocytes are stimulated to enter DNA synthesis by norepinephrine (NE). This stimulation is maximal if the hepatocytes are incubated with NE for more than 12 hr, beginning no later than 2-4 hr after the cells are first plated. After 24 hr in culture, hepatocytes are unresponsive to NE stimulation. A strong synerergistic interaction between NE and epidermal growth factor (EGF) may be observed in cultures incubated with both EGF and NE, or pretreated with NE, then exposed to EGF. This interaction may be related to the finding that NE, in similarity with other factors that enhance EGF stimulation, reduces binding at the EGF receptor during the first 24 hr in culture.

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Insulin inhibits the glucocorticoid‐mediated increase in hepatocyte EGF binding

Cited by 41 publications

References 30 publications

Transforming growth factor beta (TGF‐β) inhibits hepatocyte DNA synthesis independently of EGF binding and egf receptor autophosphorylation

Transforming growth factor beta (TGF‐β) inhibits hepatocyte DNA synthesis independently of EGF binding and egf receptor autophosphorylation

Differential expression of c-fos and c-myc protooncogenes by estrogens, xenobiotics and other growth-stimulatory agents in primary rat hepatocytes

Norepinephrine and epidermal growth factor: Dynamics of their interaction in the stimulation of hepatocyte DNA synthesis

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