Effect of thyroxine on nerve growth factor concentration in neonatal mouse brain

Abstract The effect of T4 administration on central nervous system nerve growth factor (NGF) concentration was studied in 12 day old mice. Neonatal mice received T4 (0.4 or 1.6 ug/g body weight) daily for 11 days after birth. On the 12th day, NGF concentration was measured in cerebral cortex, cerebellum and brain stem using a specific radioimmunoassay for the biologically active beta subunit of NGF; this assay is sensitive to 10–15 pg NGF. T4 administration caused a dose related decrease in mean body weight to 86% and 77% of control body weight for the low and high T4 doses respectively. Mean cerebral cortex and cerebellum weights (corrected for body weight) were significantly increased in the T4 treated mice. Brain stem weight, however, was significantly decreased. T4 (0.4 ug/g body weight) caused a significant increase in mean NGF concentration (pg/mg protein) in cerebral cortex (26%; p Brain maturation in neonatal rodents occurs largely during the first 2–4 weeks of postnatal life; and thyroid hormones are essential for the orderly and sequential progress of this maturation. Thyroid hormone excess accelerates histological and biochemical maturation of the immature central nervous system (1–3) (CNS) whereas thyroid hormone deficiency results in significant delays in the attainment of biochemical and histological landmarks of maturation (1, 2, 4). The mechanism of this thyroid hormone effect is unknown. Specific nuclear binding sites for thyroid hormones are present in high concentrations in the immature CNS (5, 6). However thyroid hormone effects observed in other thyroid hormone responsive tissues, i.e., liver and kidney, following thyroid hormone binding to specific nuclear receptors are not observed in the immature brain (7). We have previously shown that thyroxine (T4) administration to mature male mice significantly increases nerve growth factor (NGF) content and concentration in cerebral cortex, cerebellum and brain stem (8). The present studies were conducted to determine whether thyroxine influences CNS NGF during the period of neonatal brain maturation to support the hypothesis that the thyroid hormone effects on CNS maturation may be mediated by NGF.