Modulation of Thyroid Hormone Receptors by Non-Thyroidal Stimuli

Abstract

The ability of non-thyroidal stimuli to affect the binding affinity and capacity of solubilized nuclear receptors for thyroid hormones was studied in a normal homeostatic system (erythropoiesis) and a pathobiologic one (lung-ozone interaction). No significant effects on affinity were found, as Kd control values for receptors derived from rat bone marrow averaged 57 (±28) pM while experimental (hypoxic) values averaged 89 (±55) pM. Kd control values in rat lung were found to average 142 (±22) pM while average values derived from experimental protocols with ozone and methimazole were 267 (±44) pM and 161 (±35) pM respectively. Finally, Kd control values for receptors derived from cultured MEL cells averaged 19 (±2.6) pM while experimental values during exposure to DMSO or IGFl were 23 (±3.6) pM and 26 (±11) pM respectively. In contrast, binding capacity (expressed as fmoles of hormone bound per unit protein of solubilized receptor) was markedly perturbed in several tisses by various agents: ozone effects on lung were shown by an average control value of 3.3 (±0.4) as opposed to an experimental average of 28 (±1.9); and hypoxia effects on erythroid tissue were displayed by an