These studies address the control of thyroid function, the presence and timing of appearance of thyroid hormone effects and the role of EGF mediating thyroid actions in the fetus. We utilize the chronically catheterized fetal-neonatal sheep as a model for human precocial development; specifically we study 1) the ontogenesis, metabolism, and role of extraneural thyrotropin releasing hormone (TRH) in fetal thyroid function, 2) the ontogenesis of thyroid hormone receptors and postreceptor actions in the fetus and newborn, and 3) the metabolism and thyroid dependency of epidermal growth factor (EGF) in the fetus and the role of EGF in fetal growth and development. Thyroidectomized (Tx), Tx + thyroid hormone (T3) treated, and sham operated fetuses are studied to assess the effect of thyroid state. TRH metabolism is assessed by measurements of TRH, TRH analogues, pre-pro TRH mRNA, TRH degrading enzymes and TRH metabolites versus gestation age and versus thyroid state. TRH plasma production rate (PPR) and plasma TRH threshold for TSH release are measured using steady-state kinetic methods. T3 nuclear receptors (T3NR) are measured by radioreceptor assay. T3NR mRNA levels are measured using cDNA probes for different receptor types. Postreceptor actions (growth factor levels, hormone receptors, enzyme activities, etc.) are measured by standard methods. All are related to gestation age and T3NR mRNA levels are measured using cDNA probes for different receptor types. Postreceptor action (growth factor levels, hormone receptors, enzyme activities, etc.) are measured by standard methods. All are related to gestation age and T3NR binding and T3NR mRNA types are related to postreceptor actions. Tissue EGF and EGF receptors (EGFR), EGF and EGFR mRNA levels, and EGF PPR are measured versus gestation age and thyroid state. The effects of EGF on growth and development of the athyroid fetus also are studied. Our results will add importantly to knowledge about the role of thyroid hormones in fetal-neonatal development and guide decision about management of disorder of thyroid function in pregnancy and therapy of the fetus with thyroid dysfunction.
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