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A study of the hormonal regulation of tyrosine aminotransferase in cultured rat hepatocytes

Ho, Kevin Kuat Wei (1984) A study of the hormonal regulation of tyrosine aminotransferase in cultured rat hepatocytes. PhD thesis, Murdoch University.

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The effect of insulin on the inducibility of tyrosine aminotransferase has been investigated in cultured foetal (15-19 days) and postnatal (1-10 days) rat hepatocytes. Glucocorticoids induce the enzyme in cultured hepatocytes derived from rats of these different ages. Although insulin alone has no effect on enzyme activity, when cells are grown in its presence their response to glucocorticoids is markedly diminished. CyclicAMR is also an effective inducer of tyrosine aminotransferase in cultured foetal hepatocytes but less effective in cells derived from postnatal animals. Moreover, the response to cyclicAMP is unaffected by the presence of insulin in the culture media. When foetal hepatocytes are exposed to both glucocorticoids and cyclicAMP simultaneously, there is a synergistic (that is, more than additive) response to these agents, This response is also impaired by the presence of insulin.

In order to ascertain their mode of action, the effects of insulin and cyclicAMP on the glucocorticoid receptor of cultured foetal hepatocytes were investigated. The growth of these cells in the presence of insulin had no effect on glucocorticoid receptor activity. However, cyclicAMP increases receptor complexes. This effect of cyclicAMP does not appear to be simply an enhancement of receptor stability.

Finally, it has been shown that the effect of these agents on tyrosine aminotransferase activity is the result of alterations in the rate of synthesis of this enzyme. Exposure of the cells to either glucocorticoids or cyclicAMP results in a substantial increase in enzyme synthesis and, moreover, a synergistic response was evident when both were added to the culture media. Insulin alone had no effect. However, the enhancement of enzyme synthesis that results from exposure of the cells to glucocorticoid alone or with cyclicAMP is markedly diminished if the foetal hepatocytes are grown in the presence of insulin.

Item Type: Thesis (PhD)
Murdoch Affiliation(s): School of Environmental and Life Sciences
Notes: Note to the author: If you would like to make your thesis openly available on Murdoch University Library's Research Repository, please contact: Thank you.
Supervisor(s): Cake, Max, Yeoh, George and Oliver, Ivan
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