Hypothyroidism-evoked shifts in hippocampal adrenergic receptors: Implications to ischemia-induced hippocampal damage |
| |
Authors: | Hemmings Susan J. Shuaib Ashfaq |
| |
Affiliation: | (1) Department of Physiology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, Saskatchewan, Canada;(2) Department of Medicine, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, Saskatchewan, Canada |
| |
Abstract: | Hypothyroidism was induced in a group of male Fischer 344 rats by administration of 0.05% propylthiouracil (PTU) in the drinking water for 12 weeks. Control rats were not treated. Plasma levels of thyroid hormones indicated that PTU treatment had produced severe thyroid hormone deficiency. In PTU-treated rats compared to control rats, levels of total T3 and total T4 were reduced 54.5% and 53.7%; while levels of free T3 and free T4 were reduced 87.1% and 96.5%. Functional hypothyroidism was demonstrated by: (i) a 49.1% decrease in hepatic plasma membrane 1-adrenergic receptor binding, and (ii) a 11.2- fold increase in hepatic -glutamyltranspeptidase activity; relative to the expression of these parameters in control rats. Membranes were isolated from hippocampi of control, PTUinduced hypothyroid and thyroxine-replaced rats and specific adrenergic receptor binding determined by radioligand binding techniques. Hypothyrodism resulted in a shift in the balance of 1 and 2 adrenergic receptor binding by evoking: an increase in 1- adrenergic receptor binding to 1.57-fold of control levels; and, a decrease in 2-adrenergic receptor binding to 64% of control levels. Thyroid hormone replacement carried out in PTU-treated hypothyroid rats at 30 g/kg s.c. per day for the last 3 days of the 12 week PTU-treatment protocol, which reversed physical and functional hypothyroidism, reversed the observed changes in hippocampal adrenergic receptor binding, indicating them to be thyroid hormone, and not PTU, -dependent. This receptor shift evoked by hypothyroidism may, in part, explain the protective effect of hypothyroidism on ischemia-induced hippocampal damage by favoring inhibitory input and limiting excitotoxic input by catecholamines. |
| |
Keywords: | hypothyroidism rats hippocampus adrenergic receptors inhibitory protection ischemia |
本文献已被 SpringerLink 等数据库收录! |
|