Thyroid hormone regulation of rat hepatocyte proliferation and polyploidization

The liver of adult mammals contains various classes of polyploid hepatocyte s produced by a process that is partially regulated by hormones. However, i t is not well understood how the hormones affect the rate of hepatocyte pro liferation under physiological conditions. Here we have studied the specifi c roles of 3,5,3'-triiodothyronine (T-3), growth hormone (GH), and sex ster oids on the percentage of diploid nuclei in S phase and on the population o f liver tetraploid (4C) cell nuclei in several rat model systems. Gonadal s teroids had no effect on the 8 phase but account for gender differences in the 4C nuclei. Hypophysectomy in adult male rats produced a moderate decrea se in 4C nuclei that was reversed by treatment with 25 mu g T-3.kg(-1).day( -1), whereas treatment with 200 mu g human recombinant GH (hGH).kg(-1).day( -1) was ineffective. Rats made hypothyroid by methimazole treatment of dams and pups until death showed a low 8 phase and only 5% of 4C nuclei at 70 d ays of age. T-3 significantly increased the 8 phase 24 h after administrati on and restored the adult normal level of 4C nuclei after 10 days of treatm ent. hGH did not affect the 4C nuclei or the S phase in the hypothyroid rat s. These results suggest that the processes of hepatocyte proliferation and polyploidization of the rat liver are under endocrine control, with thyroi d hormones playing the essential regulatory role.