We have previously reported that a chronic pulsatile infusion of growth hormone (GH) to growth-restricted (IUGR) ovine fetuses increased fetal circulating IGF-I levels without increasing fetal growth. We hypothesised a cortisol-induced up-regulation of fetal hepatic GH-R mRNA levels, secondary increases in IGF-I mRNA levels and circulating IGF-I levels, but a down-regulation of the type 1 IGF receptor (IGF-1R) as an explanation. We therefore measured mRNA levels of genes of the somatotrophic axis by real-time RT-PCR in fetal and placental tissues of fetuses with IUGR (induced by uteroplacental embolisation from 110-116 d gestation) that received either a pulsatile infusion of GH (total dose 3.5 mg/d) or vehicle from 117-126 d, and in control fetuses (n=5 per group). Tissues were collected at 127 d (term, 145 d). Fetal cortisol concentrations were significantly increased in IUGR fetuses. However, in liver, GH-R, but not IGF-I or IGF-1R, mRNA levels were decreased in both IUGR groups. In contrast, in placenta, GH-R, IGF-I and IGF-1R expression were increased in IUGR vehicle-infused fetuses. GH infusion further increased placental GH-R and IGF-1R, but abolished the increase in IGF-I, mRNA levels. GH infusion reduced IGF-I expression in muscle and increased GH-R but decreased IGF-1R expression in kidney. IUGR increased hepatic IGFBP-1, and placental IGFBP-2 and -3 mRNA levels with no further effect of GH infusion. In conclusion, the modest increases in circulating cortisol concentrations in IUGR fetuses did not increase hepatic GH-R mRNA expression, and therefore do not explain the increased circulating IGF-I levels that we found with GH infusion, which are likely due to reduced clearance rather than increased production. We demonstrate tissue-specific regulation of the somatotrophic axis in IUGR fetuses, and a discontinuity between GH-R and IGF-I gene expression in GH-infused fetuses that is not explained by alterations in phosphorlyated STAT5b.