Delineation of atypical insulin receptors from classical insulin and type I insulin-like growth factor receptors in human placenta.
Insulin-like growth factor (IGF)-binding sites copurifying with human placental insulin receptors during insulin-affinity chromatography consist of two immunologically distinct populations. One reacts with monoclonal antibody alpha IR-3, but not with antibodies to the insulin receptor, and represents Type I IGF receptors; the other reacts only with antibodies to the insulin receptor and is precipitated with a polyclonal receptor antibody (B-10) after labelling with 125I-multiplication-stimulating activity (MSA, rat IGF-II). The latter is a unique sub-population of atypical insulin receptors which differ from classical insulin receptors by their unusually high affinity for MSA (Ka = 2 x 10(9) M-1 compared with 5 x 10(7) M-1) and relative potencies for insulin, MSA and IGF-I (40:5:1 compared with 150:4:1). They represent 10-20% of the total insulin receptor population and account for 25-50% of the 125I-MSA binding activity in Triton-solubilized placental membranes. Although atypical and classical insulin receptors are distinct, their immunological properties are very similar, as are their binding properties in response to dithiothreitol, storage at -20 degrees C and neuraminidase digestion. We conclude that atypical insulin receptors with moderately high affinity for IGFs co-exist with classical insulin receptors and Type I IGF receptors in human placenta. They provide an explanation for the unusual IGF-II binding properties of human placental membranes and may have a specific role in placental growth and/or function.
Jonas
H A
HA
University of Melbourne Department of Medicine, Royal Melbourne Hospital, Victoria, Australia.
Cox
A J
AJ
Harrison
L C
LC
D000911:Antibodies, Monoclonal; D004229:Dithiothreitol / Q000494:pharmacology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D009439:Neuraminidase / Q000494:pharmacology; D010920:Placenta / Q000032:analysis*; D011233:Precipitin Tests; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000187:drug effects; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D009439:Neuraminidase; D004229:Dithiothreitol