Receptors for insulin-like growth factors I and II in developing embryonic mouse limb bud.
Insulin-like growth factors (IGF) or somatomedins (SM) have been classically defined as promoting the actions of growth hormone in skeletal growth. IGF is divided into two groups, IGF-I and II, and are presumed to act via IGF type I (higher affinity for IGF-I and II and very low affinity for insulin) and II (higher affinity for IGF-II than I and no affinity for insulin) receptors, respectively. Recently, a switchover role of IGF-II to I during fetal to adult growth has been suggested. We have investigated the possible transitional role of IGF-II to I in a developing mouse embryonic limb bud organ culture model. In this in vitro system, limb bud develops from the blastoma stage to a well-differentiated cartilage tissue. Both IGF type I and II receptors were found to be present in limb buds at all stages of differentiation. Type I receptor decreased with differentiation while Type II receptor increased. The effect of IGF-I on [3H]thymidine and [35S]sulfate uptake by the tissue increased with differentiation while the effect of IGF-II on [3H]thymidine uptake of the undifferentiated tissue was abolished with differentiation of the tissue. The increase of the IGF-I response with decreased type I receptor may reflect an altered receptor sensitivity (occupancy) during differentiation. The decrease of the IGF-II response with increased type II receptor with differentiation may on the other hand suggest that IGF-II in differentiated tissue no longer acts as a classical growth factor. These results tend to support the hypothesis of the switchover role of IGF-I and II during fetal and adult growth, however, confirmation of the precise role of IGF-I and II in biological growth may have to wait until further studies clarifying the significance of the increased IGF type II receptor in differentiated tissue are made.
D000818:Animals; D003432:Cross-Linking Reagents; D005121:Extremities / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008970:Molecular Weight; D009024:Morphogenesis / Q000187:drug effects; D009924:Organ Culture Techniques; D011972:Receptor, Insulin / Q000378:metabolism*; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000378:metabolism*; D013388:Succinimides; D013431:Sulfates / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism
D003432:Cross-Linking Reagents; D017451:Receptors, Somatomedin; D013002:Somatomedins; D013388:Succinimides; D013431:Sulfates; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D011972:Receptor, Insulin; C019358:disuccinimidyl suberate; D013936:Thymidine