Kinetics of deoxyribonucleic acid synthesis and replication of thyrotrophs and somatotrophs during development of hypothyroidism and l-triiodothyronine treatment of hypothyroid rats

The rates of DNA synthesis and cell replication were measured in somatotrophs (St) and thyrotrophs (T₃) in vivo during the development of hypothyroidism and during T₃ treatment of hypothyroid rats. Groups of rats were killed at different times after [3H]thymidine injection for 30 days after thyroidectomy and during 20 days of T₃ treatment (10 μg/100 g BW day) of rats thyroidectomized for 30 days. The number of St and Tt per pituitary was determined by a method combining cell counting and DNA measurement in dispersed cells as well as the percentage distribution of cells at the electron microscopic level. [₃H]Thymidine incorporation into pituitary DNA was measured, and the distribution of incorporated counts among anterior pituitary cells was assessed by electron microscopic autoradiography. [3H]Thymidine incorporation into St and Tt DNA and the relative specific activity of these cell populations were then calculated. After thyroidectomy, the number of St decreased at a constant fractional rate (1.3% day1), and the percentage of labeled St decreased from 66.7% to 40.9% of labeled pituitary cells within 2 days and to only 3.5% after 30 days. St specific activity decreased progressively from 402 to 23 dpm/106 cells after 30 days. In contrast, Tt number increased 4rfold within 15 days, and this was accompanied by an increase in labeled Tt from 4.2% to 43.3% of labeled pituitary cells and a 5.2-fold increase in Tt specific activity. T₃ treatment of thyroidectomized rats resulted in oppositely directed changes in these parameters. Tt number per pituitary decreased at a constant fractional rate (3.3% day’), and this was accompanied by a progressive decrease in labeled Tt from 41.7% to 5.3% of labeled pituitary cells. Tt specific activity also decreased progressively to 11% of control after 20 days of T₃ treatment. T₃ treatment resulted in a 2-fold increase in St number within 10 days of daily T₃ injections. Labeled St increased from 4.2% to a plateau of 52-58% of labeled pituitary cells after 5 days of T₃ injection and thereafter. St specific activity increased markedly to 18.7-fold greater than control after 2 days and 40-fold greater than control after 5 days of T₃ injection. St specific activity then decreased towards control values. The different components of the cell cycle were also measured under the same experimental conditions by flow cytofluorometry. No changes from control were observed in the percentage of anterior pituitary cells in the d, S, or G2 stages of the cell cycle. This indicates that the observed changes in the rate of DNA synthesis were accompanied by comparable changes in the rates of cell division. Thyroidal state thus appears to exert both stimulatory and inhibitory influences on DNA synthesis and cell replication in these cell lines. In hypothyroidism, DNA synthesis is increased in Tt and decreased in St. During T₃ treatment, DNA synthesis and cell replication are decreased in Tt and increased in St. While replication of these cell populations is influenced by the thyroidal state, these studies do not distinguish whether the observed changes are direct effects of thyroid hormone or are secondary to other changes that occur in these thyroidal states.