Sodium ipodate increases triiodothyronine action in vivo.
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 (AxB F ratio 5.13, p less than 0.001) and liver (AxB F ratio 2.85, p less than 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.
Hays
J H
JH
Clinical Physiology Branch, Walter Reed Army Institute of Research, Washington, D.C.
Eil
C
C
Smallridge
R C
RC
D000704:Analysis of Variance; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D007487:Ipodate / Q000494:pharmacology*; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D013965:Thyroidectomy; D013972:Thyrotropin / Q000097:blood; D014284:Triiodothyronine / Q000494:pharmacology*
D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D013972:Thyrotropin; D005993:Glycerolphosphate Dehydrogenase; D007703:Peptidyl-Dipeptidase A; D007487:Ipodate