Abstract
Extract: Forty-nine litters of eight Sprague-Dawley rat pups were divided into four pups treated with 0.6 mg hydrocortisone acetate on the day of birth and four littermate controls. The mean body weight, cerebellar weight, and cerebellar DNA were significantly depressed in treated pups by 3 days of age, with all three of these measurements of growth increasing in rate around 9 days of age, but remaining well below control values throughout 15 days of age. Body weight and cerebellar DNA were maximally depressed at age 12 days (37.7% and 46.6% of control values, respectively), and cerebellar wet weight was maximally depressed to 51.5% of the control value at 9 days of age. The activity of thymidine kinase, a salvage pathway enzyme for pyrimidine biosynthesis, was found to be depressed to 80.2% and 74.1% of the control value at 3 and 6 days of age, respectively and elevated to 134% and 158% over control values at ages 12 and 15 days. The depression of thymidine kinase activity by hydrocortisone at ages 3 and 6 days followed by the overshoot of enzyme activity after steroid-induced growth suppression had subsided suggests that the thymidine kinase may be considered as having an essential regulatory function in the rate of DNA synthesis in developing brain.
Speculation: Extrapolation of these hormone-enzyme relations in developing rat cerebellum to the clinical use of glucocorticoids in acceleration of lung maturation in human premature infants suggests the possibility that concomitant effects of the steroid may be detrimental to the development of brain areas which undergo cell replication at the time the drug is administered.
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Weichsel, M. Glucocorticoid Effect upon Thymidine Kinase in the Developing Cerebellum. Pediatr Res 8, 843–847 (1974). https://doi.org/10.1203/00006450-197410000-00005
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DOI: https://doi.org/10.1203/00006450-197410000-00005
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