Benzodiazepine Receptor and Thyroid Hormones: In Vivo and In Vitro Modulation

Abstract

In rats rendered hyperthyroid by chronic treatment with L-triiodothyronine (T₃) hormone there was a 21 and 27% decrease, respectively, in the number of binding sites for [³H]flunitrazepam ([³H]FNZ) and [³H]ethyl-β-carboline-3-carboxylate ([³H]β-CCE) without changes in affinity for the two ligands. Two weeks after thyroidectomy there was a 44% increase in [³H]FNZ sites and a 17% increase in [³H]β-CCE binding sites. In vitro we found that T₃ produces a decrease in B_max and an increase in K_D, both changes being characteristic of a mixed type of inhibition. Thyroid status dramatically affected the K_i of T₃ in displacing [³H]FNZ from sites on isolated membranes of the cerebral cortex: in hypothyroid rats the K_i value was 0.9 μM, whereas in hyperthyroid rats it was 83 μM, a 92-fold difference. In control rats, the K_i was 11 μM These findings are discussed in relation to a possible modulation of benzodiazepine receptors by thyroid hormones.