Joseph V. Martin IBN 98-09943 The goal of the proposal is to clarify how thyroid hormones influence the adult mammalian brain. During growth and development, hormones from the thyroid gland enter many cell types (including brain cells) and alter protein synthesis. In adulthood, the cellular metabolic rate is accelerated by thyroid hormones entering cells of many tissues, but not in the brain. However, some of the potentially most debilitating complications of thyroid glandular disease in adulthood are due to neurological disorders, ranging from anxiety and sleep problems to seizures or coma. The preliminary evidence demonstrates that thyroid hormones bind to and influence the function of brain GABAa receptors. These proteins on the outside of neuronal membranes are responsible for cellular effects of the major inhibitory neurotransmitter (local chemical messenger between neurons), gamma-aminobutyric acid or GABA. Further preliminary work indicates effects of thyroid hormones on the whole brain electrical activity, as measured in the electroencephalogram (EEG). Experiments will be performed in rats to determine the types of effects that thyroid hormones have on the GABAa receptor binding and the subsequent cellular response. Small amounts of thyroid hormones will be injected directly into selected brain areas to ascertain the sensitivity of the sites in mediating thyroid hormonal effects on EEG and temperature regulation. The results of these studies will elucidate the biological significance of a brain action of thyroid hormones that more closely resembles the action of a neurotransmitter than the typical action of thyroid hormones in other tissues.
