The research described in this proposal is intended to define the importance of thyrotropin-releasing hormone (TRH) in the maintenance of thyrotropin (TSH) and thyroid hormone secretion in the fetus and newborn. Studies will also be performed to characterize factors related to TRH production, metabolism, and distribution in the fetus. In particular, the role of the placenta as a site of fetal TRH degradation will be studied. The studies described here will also evaluate the possibility that TRH can be used to stimulate fetal thyroid function when it is clinically desirable to accelerate thyroid hormone induced maturational events. Indirect studies will also be performed in the fetus and the adult to evaluate the effects of anesthesia on TRH secretion as it relates to thyrotropin (TSH) secretion. These studies will use somatostatin, TRH analog antagonists, and passive immunization with antiserum directed against TRH. The guinea pig has long been used in fetal research but hypothalamic-pituitary-thyroid studies are limited by the lack of a guinea pig TSH radioimmunoassay (RIA). Such an assay would be extremely helpful in improving our understanding of fetal hypothalamic-pituitary-thyroid maturation in a species similar to the human in terms of placental type and degree of maturity at birth. A guinea pig TSH RIA will, therefore, be developed. Secretions of the canine prostate contain immunoreactive TRH and deamido TRH (a TRH metabolite). Studies will be performed to determine if TRH has an independent as opposed to a neuromodulator effect on prostate glandular or contractile function. Specific pharmacologic stimuli will be used to determine if this immunoreactive TRH is produced by neuronal or epithelial cells. Chromatographic studies will be performed to determine if there is a relationship between the cell type which produces immunoreactive TRH, i.e., neuronal vs. non-neuronal, and the type of immunoreactive TRH produced, i.e, TRH homologous peptide.
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