A unique placental lactogen receptor: implications for fetal growth.

To determine whether there are structural differences between the binding sites for placental lactogen (PL) and GH, we have compared the molecular weights of complexes formed by the covalent cross-linking of [125I]ovine (o) PL and [125I]oGH to hepatic membranes from fetal and pregnant sheep in mid- and late gestation and from postnatal nonpregnant sheep at 3 days to 7 months of age. Specific [125I]oPL binding sites in fetal liver were detected as early as midgestation, and cross-linking of [125I]oPL to fetal hepatic membranes yielded a major radiographic band with a mol wt of 60 +/- 5 K (mean +/- SD). Unlabeled oPL at low concentrations (0.9-9 nM) specifically competed with [125I]oPL for binding to the 60 K complex. In contrast, oGH and oPRL competed for binding to the 60 K complex only at much higher concentrations (greater than or equal to 90 nM). In addition, no specific cross-linking of [125I]oGH or [125I]oPRL to fetal hepatic membranes was observed. These findings suggest the presence of a distinct and unique PL binding site in ovine fetal liver. Since the mol wt of oPL is 22 K, the estimated mol wt of the oPL receptor protein is 38 +/- 5 K. During the first week after birth, there was a striking increase in the number of [125I]oGH binding sites. Cross-linking of [125I]oGH to postnatal liver yielded radiographic bands with apparent mol wts of 75 K and 140 K. The relative potencies of oPL, oGH, and oPRL in competing for binding to the 75 K and 140 K complexes were similar to the relative potencies of these hormones in competing for [125I]oGH binding sites in postnatal liver, suggesting that the 75 K and 140 K bands represent subunits of the oGH receptor bound covalently to [125I]oGH. Cross-linking of [125I]oPL to pregnant and postnatal nonpregnant liver yielded three radiographic bands with mol wts of 60 K, 75 K, and 140 K. The intensities of all three bands were reduced by low concentrations (0.9-9 nM) of oPL. Higher concentrations of oGH abolished the 75 K and 140 K bands but reduced the intensity of the 60 K band by only 20-30%. oPRL had minimal effect on band intensities. These observations suggest the presence of two functionally and structurally distinct receptors in pregnant liver: the oPL receptor, which has high affinity for oPL and low affinity for oGH and oPRL.(ABSTRACT TRUNCATED AT 400 WORDS)

Duke Scholars

Author Michael Scott Freemark Pediatrics, Endocrinology