Regulation of epidermal growth factor receptor levels by thyroid hormone.
The binding of iodinated epidermal growth factor (125I-EGF) to membrane preparations from the livers of euthyroid and hypothyroid rats was examined to determine if thyroid hormones regulate EGF receptors. Binding in membrane preparations from hypothyroid livers was only 30-40% compared to that of euthyroid controls. Treatment of hypothyroid animals with a single dose of L-T3 96 h prior to sacrifice restored EGF binding nearly to the control levels. Scatchard analysis of the binding data indicated that the decrease in EGF binding in hypothyroid membranes was due to a decrease in the number of the receptors. Affinity labeling/cross-linking of 125I-EGF to hepatic membranes with disuccinimidyl suberate followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography revealed a prominent band of Mr = 170,000, which was decreased in hypothyroid samples to the same extent as EGF binding. EGF-stimulated receptor kinase activity in detergent extracts of hepatic membranes also revealed a major phosphorylated protein species of Mr = 170,000, which was also decreased in samples from hypothyroid animals to approximately the same degree as EGF binding. Binding, affinity labeling/cross-linking, and phosphorylation measurements thus indicate that the levels of hepatic EGF receptor are regulated by thyroid status. These results raise the possibility that some in vivo affects of thyroid hormones may be mediated by alterations in EGF receptor levels.
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors; D005260:Female; D007037:Hypothyroidism / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008970:Molecular Weight; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D014284:Triiodothyronine / Q000494:pharmacology*
D011956:Receptors, Cell Surface; D014284:Triiodothyronine; D004815:Epidermal Growth Factor; D066246:ErbB Receptors