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T3 as a primary hepatic mitogen.

Bungay, A.W.; (2008) T3 as a primary hepatic mitogen. Doctoral thesis , University of London. Green open access

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An exciting therapeutic goal would be to use agents in clinical practice which could increase the size of a patient's functioning hepatic tissue in times of liver disease such as in the recovery phase from liver transplantation. An increase in the size and function of the liver at times such as this would ensure a more rapid recovery and less associated liver related morbidity and mortality. As a group, the primary hepatomitogens might be employed to this end. Tri-iodothyronine (T3) is a non carcinogenic agent and a very plausible candidate to be used in this setting. T3 is one of a number of drugs which can bring about proliferation of hepatocytes in the adult liver without any preceding cell loss i.e. a process of direct hyperplasia as opposed to the compensatory regeneration one sees following hepatectomy. The work undertaken in this thesis aims to form a better understanding of the mechanism of action of the hepatomitogen tri-iodothyronine, T3. Thus far the mitogenic response is reliably modelled in vivo in the rodent but not in hepatocyte culture. This research attempts to demonstrate directly for the first time a mitogenic effect in human liver and starts with exploring T3 effects in perfused liver and then in vivo in the rodent model where gene array studies are performed to identify novel mediators of the hepatic T3 proliferative response. Potential mediators have their serial expression profiles studied over time after T3 stimulation by Real Time PCR. Finally, the role of mTOR (important in mediating cell growth and proliferative signalling pathways) is identified in mediating the hepatic mitogenic T3 response.

Type: Thesis (Doctoral)
Title: T3 as a primary hepatic mitogen.
Identifier: PQ ETD:591429
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest. Third party copyright material has been removed from the ethesis
UCL classification: UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Institute of Hepatology
URI: http://discovery.ucl.ac.uk/id/eprint/1444127
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