Role of the Thyroid Gland in the Control of Polyploid Cell Formation in the Rat Liver1

Abstract

The relationship of the thyroid gland to the control of polyploid cell formation in the rat liver was investigated in immature and in sexually mature male rats. The measurement of nuclear size and the counting of binucleated cells served as measures of polyploidy, and the presence of a polyploid DNA content was verified in one experiment by the chemical determination of the average amount of DNA per nucleus. In immature animals (50 and 68 g body weight), thyroidectomy interrupted body and liver growth, prevented the progressive accumulation of new polyploid nuclei and caused a pronounced reduction of the absolute and the relative numbers of polyploid nuclei present at the time of gland extirpation. These results were observed at postoperative intervals ranging up to 147 days. Thyroid lack also prevented the formation of binucleated cells from mononucleated diploid cells, but those already present were not reduced in numbers. Thyroidectomy in sexually mature animals (180 g body weight) prevented the accumulation of new polyploid nuclei, but did not decrease their relative numbers below the values found at the time of operation. The study of thyroidectomized castrates showed that this difference from the results observed in immature rats was not due to the presence of testicular hormones. Treatment of thyroidectomized rats with thyroxine led to body and liver growth and to the formation of increasing numbers of polyploid nuclei. Treatment with growth hormone produced similar results, despite the continuing absence of thyroid hormone. The effects of the hormones on the numbers of polyploid nuclei were roughly proportional to the amount of body and liver growth they induced. Hypophysectomy at 70 g body weight retarded but did not prevent the formation of new polyploid cells; 36 days after operation, the relative number of polyploid cells had increased. Treatment of hypophysectomized animals with thyroxine did not influence body or liver weight or the number of polyploid nuclei, whereas treatment with growth hormone increased all three. It was concluded that polyploid nuclei can arise in the absence of hormonal growth stimulation, but that thyroid hormone enhances their rate of formation, acting mainly through its effect on the release of anterior pituitary growth hormone. The results also suggest that a factor of pituitary origin, or under pituitary control, is responsible for the loss of polyploid nuclei following thyroidectomy in immature rats, and that the formation of polyploid cells during normal liver growth may be governed by antagonistic influences.