High-affinity receptor for insulin-like growth factor II in rat liver: properties and regulation in vivo.

Receptors for insulin-like growth factor II (IGF-II) have been identified in many tissue types and have been shown to differ widely in their specificities and affinities. We have characterized the IGF-II receptor in rat liver microsomal membranes, both in the intact membrane and in a solubilized extract. Binding was time- and temperature-dependent and was unaffected by changes in pH in the range 6-9. Half-maximal displacement was obtained with 0.33 ng IGF-II/ml standard, and Scatchard analysis showed a class of receptors with an affinity for IGF-II of 1.33 +/- 0.36 X 10(10) litres/mol which increased threefold in the presence of Ca (1 mmol/l) to 3.74 +/- 0.89 X 10(10) litres/mol. There was also a threefold decrease in the rate of dissociation in the presence of Ca. Cross-reactivity with IGF-I was less than 1% and there was no cross-reactivity with insulin. Infusion of rat GH or prolactin for 1 week, at the rate of 175-200 micrograms/day, into female rats had no effect on IGF-II binding in control animals, but rat GH infusion caused a 60% increase (P less than 0.001) in binding in hypophysectomized rats by increasing the number of receptors. These studies demonstrate that rat liver microsomal membranes contain a highly specific, high-affinity receptor for IGF-II which may be under partial GH control.