Down-regulation of nuclear T3 receptors by thyroid hormones in the rat anterior pituitary

Abstract

The concentration of T3 nuclear receptors may be modulated by thyroid hormones. We have examined the effect of thyroid hormone excess and deficiency in the rat on the in vitro binding of T3 to anterior pituitary nuclear receptors. Nuclei prepared from hypothyroid, hyperthyroid and control rats by homogenisation and centrifugation were incubated with [125I]T3 and unlabelled T3 at increasing concentrations. After incubation for 60 min at 37 degrees C, nuclei were separated by filtration and bound radioactivity counted. Scatchard analysis of binding data revealed no significant difference in binding affinity or capacity for T3 between nuclei from hypothyroid and control rats. Results from hyperthyroid and control animals revealed no change in affinity, but a marked reduction in binding capacity was observed, suggesting depletion of receptor number. This finding of down-regulation may represent a protective mechanism against the effects of high circulating thyroid hormone levels on the tissues.