Insulin-like growth factor receptor in fetal lamb liver: characterization and developmental changes.
Multiplication-stimulating activity (MSA), an insulin-like growth factor (IGF) (rat IGF II), binds to extracts of many tissues from fetal lambs. We now report the presence of high concentrations of a glycoprotein receptor with a high affinity for MSA-II in microsomes prepared from fetal lamb liver. The binding of radiolabeled MSA-II is inhibited by IGF but not by insulin, human, and ovine GH, ovine PRL, ovine placental lactogen, and mouse epidermal growth factor. The relative potencies of human IGF II, human IGF I, and MSA-II in competing with [125I]MSA-II for binding to this receptor are 100:17:3.5 by weight. Binding is pH, time, and temperature dependent. Gel permeation chromatography of the Triton X-100 soluble receptor indicates a hydrodynamic radius of 6.8 nm. Specific binding increases from mid- to late gestation and is associated with changes in both the affinity and concentration of receptors. Receptor concentration increases from 7.95 +/- 3.94 pmol/mg (mean +/- SE) at 78 days gestation to 15.8 +/- 4.3 pmol/mg at 134-140 days (P less than 0.05), whereas receptor affinity decreases from 1.14 +/- 0.34 X 10(9) liter/mol to 0.63 +/- 0.14 X 10(9) liter/mol over this period (P less than 0.05). The presence of very high concentrations of an IGF receptor in fetal lamb liver suggest that this organ may be a major target for IGF action in fetal life. The increase with advancing gestational age of the concentration of IGF receptors which have preferential specificity for IGF II may function to increase the responsiveness of the fetal lamb liver to IGF II stimulation and so compensate for the decline in plasma concentrations of this growth factor which occur near birth.
Owens
P C
PC
Waters
M J
MJ
Thorburn
G D
GD
Brinsmead
M W
MW
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002846:Chromatography, Affinity; D002850:Chromatography, Gel; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007335:Insulin-Like Growth Factor II; D007700:Kinetics; D008099:Liver / Q000196:embryology*; D008274:Magnesium / Q000494:pharmacology; D008862:Microsomes, Liver / Q000378:metabolism; D017830:Octoxynol; D010455:Peptides / Q000378:metabolism; D011092:Polyethylene Glycols; D011956:Receptors, Cell Surface / Q000502:physiology*; D017451:Receptors, Somatomedin; D012756:Sheep; D013696:Temperature; D013997:Time Factors
D010455:Peptides; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D011092:Polyethylene Glycols; D007335:Insulin-Like Growth Factor II; D017830:Octoxynol; D008274:Magnesium; D002118:Calcium