The effects of chronic neonatal hyperthyroidism in rats on the ontogenic pattern of serum corticosterone and growth hormone (GH) were studied. Thyroxine (T4) treated and saline injected rat pups were sacrificed under basal and stress conditions. In comparison to saline control animals, daily T4 administration (0.4 micrograms/gram body weight) produced a sustained elevation in basal corticosterone levels by day 12 and a significant elevation of serum corticosterone in response to stress by day 4. The serum GH levels in non-stressed animals were moderately decreased in response to T4 administration as compared to saline injected animals with a greater reduction in GH measured in samples obtained from stressed animals. The results indicate that chronic T4 administration influences the developmental pattern of serum corticosterone and GH under both non-stress and stress conditions.

Experimental hyperthyroidism in the neonatal rat is known to accelerate cerebellar DNA biosynthesis resulting ultimately in a deficit in cell number at maturity. Because of the known shift to an earlier age in the developmental curve for cerebellar thymidine kinase activity in rats treated with thyroxine, we studied the activity of uridine kinase and DNA biosynthesis during rat cerebellar development under hyperthyroid conditions. Body weight and cerebellar wet weight in treated animals were noted to be significantly decreased below control values on days 4 and 12, respectively. Cerebellar DNA was significantly elevated above control values on days 4 and 6 (132 and 129 % of control, respectively). Subsequently, DNA content fell significantly below control values through day 18. Uridine kinase activity was found to be increased significantly above control values at ages 2, 4, and 6 days (maximum 119% of control at age 4 days) following which activity fell significantly below control values by 15 days of age. Uridine kinase activity from both treated and control animals fell only moderately after the time of peak activity between 9 and 15 days of age, although the peak of the developmental curve for the enzyme appeared earlier in the treated animals. The data show a less pronounced early stimulation of cerebellar uridine kinase by thyroxine compared with previously reported thyroxine enhancement of thymidine kinase activity, although both enzymes are affected by thyroxine throughout cerebellar ontogenesis. The study thus provides evidence that uridine kinase is sensitive to hormonal stimulation during early stages of active cerebellar cell division, and that the enzyme may relate most closely in brain to the synthesis of RNA as well as the sustaining of cell function after the most active phase of cellular proliferation. In addition, the study emphasizes the use of enzyme-hormone relationships during development to provide information concerning critical interrelationships between metabolic pathways contributing to nucleic acid biosynthesis.