Binding of Proinsulin and Proinsulin Conversion Intermediates to Human Placental Insulin-Like Growth Factor I Receptors*

Insulin-like growth factor I (IGF-I) and proinsulin share similarities in both primary and tertiary structure. Proinsulin, endogenously secreted or exogenously administered, would, therefore, be expected to interact with IGF-I receptors. We determined the relative activities of IGF-I, insulin, proinsulin, and the proinsulin conversion intermediates in IGF-I radioreceptor assays using term human placental membranes. Insulin was approximately 0.5% as potent as IGF-I, and proinsulin was only 2% as potent as insulin. The six major proinsulin conversion intermediates were studied; all had activities intermediate between those of insulin and proinsulin. We conclude that the binding of proinsulin and the proinsulin conversion intermediates to IGF-I receptors is not of physiological significance at the concentrations occurring endogenously or after exogenous administration of proinsulin.