CHARACTERISTICS OF HUMAN FETAL HEPATIC RECEPTORS FOR INSULIN (INS) AND SOMATOMEDIN-C (SM-C)

Abstract

The roles of Ins and Sm-C as stimulators of cellular metabolism and growth in the human fetus remain controversial. Since the effects of these hormones are initiated by their interaction with specific cell surface receptors, the binding and structural characteristics of the Ins and Sm-C receptors were examined in second trimester fetal hepatic membranes (FHM). A membrane-rich homogenate was prepared from frozen human fetal livers provided by the National Diabetes Research Interchange. Hormone binding was assessed by incubating the FHM for 14h at 4C with either ¹²⁵I-Ins or ¹²⁵I-Sm-C (generously provided by J VanWyk, Chapel Hill, NC) with and without native hormone. Specific binding by FHM at 12,16, and 20 weeks gestation was 10-11% for ¹²⁵I-Ins and 5-7% for ¹²⁵I-Sm-C. Dose response curves for the Ins receptor generated curvilinear Scatchard plots with 50% of the ¹²⁵I-Ins displaced by 0.75-1.2 × 10⁻⁹ M native Ins. When FHM were affinity labeled using the crosslinking agent, disuccinimidyl suberate and analyzed by SDS-polyacrylamide gel electrophoresis followed by autoradiography, the receptors for both Sm-C and Ins had apparent MWs > 250K. After disulfide bond reduction a 135K radioactive band predominated. The results of binding studies and affinity-labeling were similar at all three gestational ages. Conclusions: 1) Second trimester human FHM possess specific Ins receptors with subunit structures similar to that described in adult tissues. 2) There is no change in Ins receptor binding or subunit structure over 12-20 weeks gestation. 3) Sm-C receptors structurally similar to the Ins receptor are also present on human HFM.

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