Evidence against a major role of L-thyroxine at the pituitary level: studies in rats treated with iopanoic acid (telepaque).

To determine whether T4 has an intrinsic effect at the pituitary level, it would be important to block conversion of T4 to T3 completely. We have attempted to achieve this with iopanoic acid (IOP), a radiographic contrast agent. We have then measured in the same animals the effects of such treatment on the conversion of T4 to T3 or on the deiodination of T3 and on the pituitary response to a dose of T4 or T3. Plasma TSH levels and pituitary GH content were measured as biological end points. Thyroidectomized rats were injected with a single dose of T4 (1.7 micrograms/100 g BW) labeled with [125I]T4 (Exp A) or with a single dose of T3 (0.33 microgram/100 g BW) labeled with [125I]T3 (Exp B) and treated with IOP or solvent. Animals of Exp A were killed 24 h after iodothyronine injection and those of Exp B were killed 4, 12, and 24 h after injection of the iodothyronine. The concentrations of [125I]T4 and [125I]T3 were measured in several tissues, including the anterior pituitary, after extraction and paper chromatography and quantified with the aid of 131I-labeled markers added in vitro. Plasma and pituitary T3 and T4 plasma TSH, and pituitary GH were measured by specific RIAs. Results show that treatment with IOP markedly inhibits the conversion of T4 to T3 and the deiodination of T3. In IOP-treated thyroidectomized rats, the injection of T4 results in little, if any, effect at the pituitary level, despite an almost 3-fold increase in the percentage of injected T4 found in the gland. Treatment with IOP does not inhibit the effects of a T3 dose; if anything, they appear to be enhanced. It is concluded that, as assessed from biological responses involving the anterior pituitary, a dose of T4 has little if any effect other than that which can be attributed to the T3 generated from it.