DNA SYNTHESIS AND THYMIDINE KINASE ACTIVITY DURING CEREBELLAR DEVELOPMENT: EFFECT OF THYROXINE

Abstract

Thyroid hormone administered from birth has been found to increase cerebellar DNA production in the rat by 6 days of age and to decrease DNA synthesis thereafter. This acceleration of development under hormonal influence has led to studies involving the relationship between thyroxine, DNA and activities of enzymes involving pyrimidine biosynthesis during cerebellar development. Using daily doses of thyroxine, we found rat cerebellar DNA to be increased significantly above control values by age 2 days until age 6 days. Following that, cerebellar DNA synthesis decreased to 78% of control values by age 12 days. The activity of thymidine kinase, a salvage pathway enzyme for pyrimidine biosynthesis, was found to be significantly elevated over control values by age 1 day. This elevation of enzyme activity in cerebella of treated animals continued until age 5 days, at a maximum of 137% of control values, following which activity fell significantly below control values by 9 days of age. Thyroxine thus appears to induce thymidine kinase activity in early cerebellar development and is apparently related to premature decrease of activity. These findings provide evidence that thymidine kinase may be subject to hormonal control, and may be a critical regulatory enzyme for cerebellar DNA biosynthesis.