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Thyroid-dependent maturation of neonatal brain but not lung epidermal growth factor receptors
Insights
Thyroid hormones influence brain and lung development by affecting epidermal growth factor (EGF) receptors. Hypothyroidism reduces EGF receptors in the neonatal brain, while hyperthyroidism increases them, suggesting a role for EGF in maturation.
Area of Science:
- Endocrinology
- Developmental Biology
- Neuroscience
Background:
- Thyroid hormones are crucial for perinatal lung and brain maturation.
- Cellular mechanisms underlying these developmental processes are not fully understood.
- Hypothyroidism is known to impair the development of various receptors in fetal and neonatal tissues.
Purpose of the Study:
- To investigate the impact of experimentally induced hypo- and hyperthyroidism on epidermal growth factor (EGF) receptor development in neonatal rabbit brains and lungs.
- To elucidate the role of thyroid status in regulating EGF receptor expression and function during neonatal development.
Main Methods:
- Rabbit pups were made hypothyroid using propylthiouracil or hyperthyroid using thyroxine administration during gestation.
- Plasma free thyroxine (T4) levels were measured using radioimmunoassay.
- Brain and lung plasma membranes were isolated, and EGF receptor characteristics were analyzed using 125I-EGF binding assays and Scatchard analysis.
Main Results:
- Hypothyroidism significantly decreased EGF receptor binding and number in neonatal brain plasma membranes, while hyperthyroidism increased them.
- In contrast, EGF receptor binding and number in lung plasma membranes remained unaffected by altered thyroid states.
- Scatchard analysis indicated no significant change in the dissociation constant (Kd) for EGF receptors in the brain.
Conclusions:
- Neonatal brain EGF receptor development is sensitive to thyroid hormone levels.
- Thyroid hormones may modulate brain maturation through the regulation of EGF receptor expression.
- The findings support a role for EGF in neonatal brain and lung development, with thyroid status specifically impacting brain EGF receptor dynamics.
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. Hypothyroidism retards the development of fetal pulmonary insulin, neonatal pulmonary beta-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 micrograms/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 less than 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 125I-EGF to 200 micrograms of brain plasma membrane (BPM) protein was significantly lower in the hypothyroid (0.62 +/- 0.03, n = 7, p less than 0.01), and higher in the thyroxine-treated (1.58 +/- 0.08, n = 6, p less than 0.01) group when compared to control (1.08 +/- 0.06, n = 6) animals. However, the percent specific binding of 125I-EGF to 100 micrograms 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 EGF may play an important role in neonatal brain and lung maturation.(ABSTRACT TRUNCATED AT 400 WORDS)