Thyroid-Dependent Maturation of Neonatal Brain but Not Lung Epidermal Growth Factor Receptors

Abstract

Although the role of thyroid hormones in enhancing lung and brain maturation during the perinatal period is well established, the cellular mechanisms involved in these processes are incompletely understood. Flypothyroidism retards the development of fetal pulmonary insulin, neonatal pulmonary ß-adrenergic and neonatal brain insulin receptors. In this study, we investigated the effect of hypo- or hyperthyroidism on the development of neonatal brain and lung epidermal growth factor (EGF) receptors. The rabbit pups were rendered hypothyroid by adding 0.05 % propylthiouracil to the drinking water starting at 23 days of gestation and thereafter. The neonatal hyperthyroid state was achieved by intramuscular administration of 100 µg/kg of synthroid to the rabbit doe on the 29th and 30th day of pregnancy. Neonatal plasma free thyroxine (T4) concentrations were quantitated by a radioimmunoassay. Brain and lung plasma membranes were isolated by differential centrifugation. EGF receptor characteristics were studied using 125I-EGF binding assays and Scatchard analysis. The plasma free T4 concentrations were 0.36 ± (SEM) 0.02 (n = 6), p < 0.01 (n = 7) and 1.76 ± 0.1 (n = 6) ng/dl in the control, hypothyroid and hyperthyroid pups, respectively. The percent specific binding of l25I-EGF to 200 pg of brain plasma membrane (BPM) protein was significantly lower in the hypothyroid (0.62 ± 0.03, n = 7, p <0.01), and higher in the thyroxine-treated (1.58 ± 0.08, n = 6, p < 0.01) group when compared to control (1.08 ± 0.06, n = 6) animals. Flowever, the percent specific binding of l25I-EGF to 100 pg of lung plasma membrane (LPM) protein was similar in all three groups (2.24 ± 0.28, control; 2.01 ± 0.5, hypothyroid, and 2.26 ± 0.3, hyperthyroid). The number of EGF receptors per milligram of BPM protein (X 10-^10) were lower in the hypothyroid (2.24 ± 0.03, n = 5) and higher in the hyperthyroid (6.6 ± 0.02, n = 4) group when compared to control (4.4 ± 0.05, n = 4) with no apparent difference in Kd. There was no difference in the number of EGF binding sites per milligram of LPM protein (X 10-10) within the groups (6.6 ± 0.8. n = 6, control; 7.9 ± 0.4, n = 4, hypothyroid, and 7.3 ± 0.3, n = 4, hyperthyroid). Presence of high affinity receptors for EGF in the neonatal brain as well as lung supports the hypothesis that EG F may play an important role in neonatal brain and lung maturation. Thyroxine may influence neonatal brain but not lung maturation through its interaction with the development of EGF receptors.