Sodium ipodate increases triiodothyronine action in vivo

Abstract

Sodium ipodate (IPO) has been shown to bind nuclear T₃ receptors (NT₃R) in vitro, but previous studies have conflicted in regard to demonstration of this interaction in vivo. We sought evidence for IPO-NT₃R binding in vivo by giving large doses of IPO to thyroidectomized (TDX) rats replaced with low doses of T₃. We predicted that IPO-NT₃R binding would inhibit T₃ induced increases in mitochondrial alpha glycerophosphate dehydrogenase activity (alpha-GPDH) in kidney, heart and liver. Three groups of ten euthyroid rats each received 13 daily injections of vehicle, or 6 or 12 mg/100 g body weight of IPO, respectively. Both doses of IPO resulted in decreases in serum T₃ and increases in serum TSH. Liver and kidney alpha-GPDH, however, were decreased only in the group receiving 6 mg IPO. In addition, three groups of 30 TDX rats were implanted with osmotic minipumps that contained T₃ in the following concentrations: 33, 69 and 96 ng/ul. Ten rats in each group received 13 daily injections of vehicle, or IPO (vide supra). The alpha-GPDH responses were complex in that there was significant interaction between T₃ and IPO effects in the kidney (A×B F ratio 5.13, p<0.001) and liver (A×B F ratio 2.85, p<0.05). The major finding, however, was that alpha-GPDH was not significantly reduced by IPO in any T3 replaced group. Rather, in all three organs, alpha GPDH was significantly increased above that produced by T₃ alone by at least one combination of IPO and T₃. Changes in serum TSH also suggested that IPO could enhance T₃ effects. We conclude that IPO-NT₃R binding is not a prominent mechanism via which the drug attenuates T₃ effects in vivo. The data suggest that IPO may enhance T₃ effects at the cellular level and that this enhancement may not be reflected by routinely monitored serum TSH. The latter observation may have clinical importance.