Control of ovine hepatic growth hormone receptor and insulin-like growth factor I by thyroid hormones in utero

By use of RNase protection assays, hepatic growth hormone receptor (GHR) an d insulinlike growth factor I (IGF-I) mRNA abundances were measured in shee p fetuses after experimental manipulation of fetal plasma thyroid hormone c oncentrations by fetal thyroidectomy (TX) and exogenous infusion of triiodo thyronine (T-3) and cortisol. TX abolished the normal prepartum rise in hep atic GHR abundance but had little effect on hepatic GHR gene expression at 127-130 days (term 145 +/- 2 days). By contrast, it upregulated basal IGF-I expression in immature fetal liver by increasing both Class 1 and Class 2 transcript abundance but had no further effects on IGF-I gene mRNA levels a t 142-145 days. Raising plasma T-3 to prepartum values by exogenous infusio n of either T-3 or cortisol into immature intact fetuses prematurely raised hepatic GHR and IGF-I mRNA abundances to values similar to those seen in i ntact fetuses at 142-145 days. In TX fetuses, cortisol infusion increased h epatic GHR mRNA but not total IGF-I mRNA abundance at 127-130 days. These f indings show that thyroid hormones have an important role in the regulation of hepatic GHR and IGF-I gene expression in fetal sheep during late gestat ion and suggest that T-3 mediates the maturational effects of cortisol on t he hepatic somatotropic axis close to term.