Thyroid Hormone Treatment of Hypothyroid Rats Restores the Regenerative Capacity and the Mitochondrial Membrane Permeability Properties of the Liver after Partial Hepatectomy

Abstract

We have investigated the effect of thyroid hormone on recovery of liver mass and on the mitochondrial membrane permeability properties during rat liver regeneration after 70% partial hepatectomy (PH). In the euthyroid state, liver weight starts to recover 24 h after PH and is completely restored 96 h after PH. Cyclosporin A (CsA)-sensitive mitochondrial permeability transition (MPT) occurs 24 h after PH, and it has been suggested to act in the signaling mechanism for hepatocyte proliferation. In this study we show that hypothyroidism delays recovery of the liver mass, being only 50% of the initial weight 96 h after PH, and alters the duration and mode of MPT occurrence, first inducing a CsA-insensitive swelling 24 h after PH, followed by a CsA-sensitive swelling 96 h after PH. The occurrence of both CsA-sensitive and -insensitive swelling is shown to be associated with an increase in mitochondrial calcium content. Concurrent with mitochondrial swelling, external release of matrix proteins from mitochondria, such as aspartate aminotransferase and malate dehydrogenase, is shown to be CsA insensitive 24 h after PH and CsA sensitive 96 h after PH. After thyroid hormone administration to hypothyroid rats, the liver regenerative capacity is restored, and the duration and mode of MPT occurrence as well as changes in mitochondrial calcium content become similar to those observed in the euthyroid condition. The results of the present study suggest the involvement of a mitochondria-mediated pathway in regulation of the liver regenerative process by thyroid hormone.

Supplementation of curcumin and vitamin E enhances oxidative stress, but restores hepatic histoarchitecture in hypothyroid rats

“…Hypothyroidism is a prevalent disorder associated with low oxygen utilization and low tissue proliferation rate (Moro et al, 2004). In the present study, PTU was observed to induce decrease in hepatocyte nuclei in Group II rats, which was evident from the decreased nuclear count.…”

Thyroid Status Affects Rat Liver Regeneration After Partial Hepatectomy by Regulating Cell Cycle and Apoptosis

“…It has been demonstrated that a single dose of T3 enhances DNA-synthesis and regenerative capacity of the liver after PH [38,39]. Consistent with these findings, recently it has been reported that although hypothyroid rats are able to regenerate their liver mass completely, the recovery is significantly delayed; whereas T3 administration to hypothyroid rats restores the liver regenerative capacity [40].…”

The Nuclear Receptor Constitutively Active/Androstane Receptor Regulates Type 1 Deiodinase and Thyroid Hormone Activity in the Regenerating Mouse Liver

“…It is also well established that thyroid hormone can increase the growth of the liver after PH because injection of T3 into mice after PH increases the rate of liver regeneration (Moro et al, 2004;Alisi et al, 2005). It does not appear that CAR directly regulates the levels of T3, although ability of CAR to regulate the levels of rT3 may be akin to regulation of T3 itself.…”