Malik, Raza; (2004) Characterisation of tri-iodothyronine as a primary mitogen for the liver. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Hepatocyte proliferation can be induced in one of two distinct processes, COMPENSATORY REGENERATION and DIRECT HYPERPLASIA. In compensatory regeneration, the initial event is hepatic injury (chemical/viral) or surgical resection with a reduction in liver mass. These events are followed by proliferation, initially of hepatocytes and then other cell populations of the liver, to rapidly restore the normal precisely regulated liver mass. In contrast, in direct hyperplasia, hepatocytes are stimulated to proliferate by primary mitogens in the absence of liver injury or resection, resulting in an increase in liver mass to above the normal value. In this thesis we have characterised the effects of thyroid hormone as a primary mitogen for the rat liver, with particular reference to its potential exploitation within the fields of hepatic and transplant surgery. We have demonstrated that a single injection of tri-iodothyronine, initiates proliferation in hepatocytes, and 96h later over 30% of the hepatocytes (predominantly midzonal) have gone through S-phase and cell division. The less well-recognised property of T3 was the potential of the intact liver to grow in vivo to a size and more importantly to a functional capacity greater than normal. We have shown that the simultaneous co-administration of tri-iodothyronine with 70% partial hepatectomy increases the proliferative response of hepatocytes following surgery, and thus enhances regeneration during one of the strongest known stimuli to hepatocyte proliferation. In the final chapters we have attempted to identify a mechanism for this intriguing phenomenon and tried to develop an in vitro model of T3 function. The overall aim of this project was to determine whether regimes administering thyroid hormone could provide a useful enhancement of liver function in man.

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