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Characteristics of Hepatic Receptors for Somatomedin C/Insulin-Like Growth Factor I and Insulin in the Developing Human^*

STEVEN D. CHERNAUSEK, DOROTHY C. BEACH, WALTER BANACH and MARK A. SPERLING

Division of Endocrinology, Department of Pediatrics, Children’s Hospital Medical Center, University of Cincinnati Medical Center Cincinnati, Ohio 45229

Insulin and the somatomedins (Sms) are putative regulators of cell proliferation and metabolism in the fetus. Since the liver is a potential target tissue of these hormones during fetal life, we characterized the hepatic receptors for Sm-C/insulin like growth factor I (Sm-C/IGF-I) and insulin during the second trimester of human fetal development. Membrane-enriched fetal liver homogenates specifically bound 8.9 ± 1.5% (±SD) of added [¹²⁵I]insulin and 5.1–7.2% of [¹²⁵I]Sm-C/IGF-I. Binding of both hormones was constant from 12–20 weeks gestation and was much greater than that in adult liver membranes. Analysis of dose-response data indicated high affinity between each receptor and its respective ligand (K_d for the Sm-C/IGF-I receptor, 2.2 x 10^–10 M; K_d for insulin receptor, 5.2 x 10^–10 and 7.7 x 10^–9 M). Limited cross-reactivity (1:1,000) of insulin with the Sm-C/IGF-I receptor and Sm-C/IGF-I with the insulin receptor was found. Affinity labeling studies showed that each receptor possessed an approximately 135,000-dalton subunit which was a part of a larger disulfide-linked complex. Thus, the human fetal liver has specific receptors for Sm-C/IGF-I and insulin that are similar to those described for other tissues in terms of both hormone-binding characteristics and subiinit structure, suggesting that these receptors mediate important cellular functions at this stage of fetal development.

^* This work supported in part by Biomedical Research Support Grant RR-05408-21, a grant from the Children’s Hospital Research Foundation, and USPHS Grant HD-12613.

To whom all correspondence and requests for reprints should be addressed.

Received September 15, 1986.

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