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) and insulin-like growth factor I (IGF-I) mRNA abundances were measured in sheep fetuses after experimental manipulation of fetal plasma thyroid hormone concentrations by fetal thyroidectomy (TX) and exogenous infusion of triiodothyronine (T(3)) and cortisol. TX abolished the normal prepartum rise in hepatic 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 at 142-145 days. Raising plasma T(3) to prepartum values by exogenous infusion 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 intact fetuses at 142-145 days. In TX fetuses, cortisol infusion increased hepatic GHR mRNA but not total IGF-I mRNA abundance at 127-130 days. These findings show that thyroid hormones have an important role in the regulation of hepatic GHR and IGF-I gene expression in fetal sheep during late gestation and suggest that T(3) mediates the maturational effects of cortisol on the hepatic somatotropic axis close to term.
Forhead
A J
AJ
Department of Physiology, University of Cambridge, Cambridge CB2 3EG, United Kingdom. alf1000@cam.ac.uk
Li
J
J
Saunders
J C
JC
Dauncey
M J
MJ
Gilmour
R S
RS
Fowden
A L
AL
D000818:Animals; D005260:Female; D005786:Gene Expression Regulation; D006854:Hydrocortisone / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008099:Liver / Q000196:embryology* / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D011986:Receptors, Somatotropin / Q000235:genetics*; D012756:Sheep; D013963:Thyroid Hormones / Q000502:physiology*; D013965:Thyroidectomy; D014284:Triiodothyronine / Q000494:pharmacology
D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D013963:Thyroid Hormones; D014284:Triiodothyronine; D007334:Insulin-Like Growth Factor I; D006854:Hydrocortisone