Author:
Breier B H,Ambler G R,Sauerwein H,Surus A,Gluckman P D
Abstract
Abstract
While the GH receptor (GHR) plays a key role during adult life, its role during fetal development is not well understood. Recent data suggest that GHRs are present in ovine fetal hepatic tissue at mid-gestation. However, the levels of GHR expression are markedly lower in fetal hepatic tissue in comparison with postnatal values. The present study investigates whether the neonatal induction of the hepatic GHR and plasma levels of IGF-I follow a pattern of strictly age-related development or whether birth-associated processes stimulate this increase.
Stereotaxic electrolytic lesioning of the fetal paraventricular nuclei was employed to prolong gestation markedly. We compared the hepatic binding of ovine placental lactogen (oPL) and oGH and plasma levels of IGF-I in these post-mature fetuses with those in pre-term fetuses, pregnant mothers and lambs which were of the same conceptional age as the post-mature fetuses. While specific binding of both 125I-labelled oGH and 125I-labelled oPL to hepatic microsomal membranes was fully reversible in all groups, the specific binding of 125I-labelled oGH was significantly (P<0·001) lower than specific binding of 125I-labelled oPL in all groups of animals. There was no difference in specific I-labelled oGH or 125I-labelled oPL binding in livers or plasma levels of IGF-I in post-mature fetuses in comparison with pre-term fetuses. In contrast, a major increase (P<0·001) in 125I-labelled oGH and 125I-labelled oPL binding and plasma IGF-I levels was observed in lambs. In pregnant females, specific 125I-labelled oGH and 125I-labelled oPL binding and plasma IGF-I levels were significantly (P<0·01) higher compared with the two fetal groups. A significant (P<0·001) correlation was observed between specific binding with 125I-labelled oGH and 125I-labelled oPL (r=0·95, intercept=4·5, slope=2·36). Detailed competitive binding studies showed that the potency of unlabelled oPL in competing with 125I-labelled oPL or 125I-labelled oGH was consistently higher in comparison with unlabelled oGH. The differences in cross-reactivity of oPL and oGH at the distinct developmental stages were related to the differences in affinity between the two ligands and major developmental increases in capacity.
The present study shows major parallel induction of oPL and oGH binding to hepatic microsomal membranes and plasma IGF-I concentrations after birth. The postnatal increase in the hepatic GHR is inhibited if delivery is prevented by stereotaxic destruction of the fetal paraventricular nuclei. Our observation that oGH and oPL binding is co-ordinately induced after birth in hepatic tissue supports the emerging evidence that the two ligands may bind to the same membrane receptor or to related protein(s).
Journal of Endocrinology (1994) 141, 101–108
Subject
Endocrinology,Endocrinology, Diabetes and Metabolism
Cited by
45 articles.
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