Porcine Fetal Hypothyroidism Induces Temporal and Tissue-Specific Alterations in the Insulin-Like Growth Factor System.

To characterize the interaction between the fetal thyroid and IGF system, we utilized a temporal model of porcine fetal hypothyroidism. N = 24 pregnant gilts were split into two treatment groups, with 12 gilts receiving a daily oral dose of 5 mg/kg methimazole (MMI) to induce fetal hypothyroidism, and 12 gilts serving as a control. Within each group, three gilts began treatment at gestational Days 34, 45, 55, or 65 of gestation, with gilts euthanized 21 days later to allow for fetal sample collection. Fetuses from the MMI groups were confirmed hypothyroid by the presence of goiter, as well as reduced circulating thyroxine levels at all four timepoints, and reduced circulating triiodothyronine levels at the two later timepoints. Samples of fetal liver and kidney were taken from four fetuses per litter for assessment of gene expression, and IGFBP levels were also assessed in serum. Among control fetuses, many of the IGFBPs were temporally regulated throughout gestation in the liver, kidney, and serum, with the expression of IGF1 also temporally regulated. Within each timepoint, temporal downregulations in the expression of hepatic IGFBP1, -2, -3, -4, -6, and -7, as well as renal IGFBP3 and -7 were observed in MMI fetuses, with no changes in the expression of either IGF ligand. In contrast, MMI treatment resulted in minimal changes in sera IGFBP levels. These results suggest a temporal and tissue-specific relationship between thyroid hormones and the IGF system in the fetal pig, but provide little evidence of systemic disruptions in the IGF system in response to fetal hypothyroidism.