Hypothyroidism-evoked shifts in hippocampal adrenergic receptors: implications to ischemia-induced hippocampal damage.
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 alpha1-adrenergic receptor binding, and (ii) a 11.2-fold increase in hepatic gamma-glutamyltranspeptidase activity; relative to the expression of these parameters in control rats. Membranes were isolated from hippocampi of control, PTU-induced hypothyroid and thyroxine-replaced rats and specific adrenergic receptor binding determined by radioligand binding techniques. Hypothyroidism resulted in a shift in the balance of alpha1 and beta2 adrenergic receptor binding by evoking: an increase in alpha1-adrenergic receptor binding to 1.57-fold of control levels; and, a decrease in beta2-adrenergic receptor binding to 64% of control levels. Thyroid hormone replacement carried out in PTU-treated hypothyroid rats at 30 microg/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.
Hemmings
S J
SJ
Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Shuaib
A
A
D000818:Animals; D006624:Hippocampus / Q000293:injuries / Q000503:physiopathology*; D007037:Hypothyroidism / Q000139:chemically induced / Q000503:physiopathology*; D007511:Ischemia / Q000503:physiopathology*; D008099:Liver / Q000502:physiology; D008297:Male; D011441:Propylthiouracil / Q000008:administration & dosage; D051381:Rats; D011916:Rats, Inbred F344; D011941:Receptors, Adrenergic / Q000378:metabolism*; D015427:Reperfusion Injury / Q000517:prevention & control; D013963:Thyroid Hormones / Q000097:blood / Q000378:metabolism / Q000502:physiology
D011941:Receptors, Adrenergic; D013963:Thyroid Hormones; D011441:Propylthiouracil