The importance of thyroid hormones in the regulation of the Growth Hormone (GH)-IGF-1 axis is well established. T3 stimulates rat GH gene transcnption and this effect is antagonized by IGF-I, a factor that is under GH control. In turn, T3 stimulates the release and synthesis of  IGF-1 in the rat liver. Although the impact of GH or IGF-1 administration on thyroid function has been studied with controversial results the effect of these growth factors on the specific metabolic response of T3 in target tissues has not been extensively explored. In previous studies we have demonstrated that IGF-1 and GH incorporated to cultured rat hepatocytes induced a dose-dependent reduction of mitochondrial alfa-glycerophosphate dehidrogenase (alfa-GPD) and cytosolic malic enzyme (ME) activities, two useful biomarkers of thyroid hormone action. Since the maxlmal enzyme activity induced by a high T3 concentration in the culture medium was significantly reduced in the presence of IGF -I, we speculated on the possibility that such response might be reflecting a diminished number of nuclear T3 binding sites. Accordingly, using an in vivo model we aimed to further explore the mechanism by which IGF-1 affects thyroid hormone action. Recombinant human IGF-1 (60, 120, 240 and 480 ug/100g b w ) was injected s.c. twice a day during two days to adult male Wlstar rats.  Mitochondrial alfa-GPD and cytosolic ME were measured in liver cellular fractions. Maximal binding capacity (MBC) of T3 to nuclear receptors and the apparent affinity constant (Ka) were carried out in isolated liver nuclei. A significant dose-dependent reduction of alfa-GPD and ME activities was induced by IGF-1. In turn, IGF~1 In a dose of 240 ug/l00g b.w. significantly (p<0. 01) reduced de number of T3 nuclear receptors (fmol T3/100ugDNA+/-SEM: 27.30 +/- 6.50 vs control 73.19 +/- 14.07; n: 7). The Ka of nuclear receptors for T3 remain unchanged 10  9 M-1+/- SEM: SEM 2 .9+/- 0 74 vs control 2.50 +/- 0.77; n: 7). We conclude that IGF-1 was able to impair the specific metabolic response of T3 in the liver of the rat. The mechanism of the effect involves at least in part a reduction of the nuclear T3 receptor number.  These results are furlher evidences supporting a role of IGF-1 in the regulation of the GH-IGF-l/thyroid hormone axis.