Background/Aims: To investigate changes in free insulin-like growth factor I (IGF-I) and IGF-binding protein 1 (IGFBP-1) complexed IGF-I during human pregnancy. Methods: Overnight fasting serum was obtained in a longitudinal design from 11 women with non-complicated pregnancy at gestation weeks 6–10, 16–20, 24–28 and 35–38 and, for comparison, 5 weeks post-partum. All samples were analyzed for total and free IGF-I and IGF-II, IGFBP-3 and IGFBP-3 proteolysis, total and non-phosphorylated (np-) IGFBP-1, and IGFBP-1 complexed IGF-I. Results: Total IGF-I was increased in late pregnancy (week 35–38) (p < 0.001), whereas free IGF-I was significantly increased by 77% already at week 6–10 (p = 0.004) and by 140% (p = 0.002) at week 34–38, when compared to post-partum levels. At weeks 16–20 and 24–28, levels of free IGF-I were not significantly different from post-partum levels. Significant IGFBP-3 proteolysis was detectable from week 6–10 and throughout pregnancy (p < 0.05). Total and np-IGFBP-1 were significantly increased from 16–20 weeks of pregnancy (both p < 0.05) and IGFBP-1 complexed IGF-I was increased 2-fold from week 16–20 and throughout pregnancy (p < 0.05). However, the saturation of IGFBP-1 remained constant at 27–29% during the study. Conclusion: We found evidence of increased free IGF-I and increased IGF-I in binary complexes during pregnancy, possibly caused by IGFBP-3 proteolysis and decreased ternary complex formation.

1.
Frystyk J, Højlund K, Rasmussen KN, Jørgensen SP, Wildner-Christensen M, Ørskov H: Development and clinical evaluation of a novel immunoassay for the binary complex of IGF-I and IGF-binding protein-1 in human serum. J Clin Endocrinol Metab 2002;87:260–266.
2.
Baxter RC: Insulin-like growth factor binding proteins as glucoregulators. Metabolism 1995;44(suppl 4):12–17.
3.
Mirlesse V, Frankenne F, Alsat E, Poncelet M, Hennen G, Evain Brion D: Placental growth hormone levels in normal pregnancy and in pregnancies with intrauterine growth retardation. Pediatr Res 1993;34:439–442.
4.
Wilson DM, Bennett A, Adamson GD, et al: Somatomedins in pregnancy: A cross-sectional study of insulin-like growth factors I and II and somatomedin peptide content in normal human pregnancies. J Clin Endocrinol Metab 1982;55:858–861.
5.
Caufriez A, Frankenne F, Englert Y, et al: Placental growth hormone as a potential regulator of maternal IGF-I during human pregnancy. Am J Physiol 1990;258:E1014–E1019.
6.
Caufriez A, Frankenne F, Hennen G, Copinschi G: Regulation of maternal insulin-like growth factor I by placental growth hormone in pregnancy. Possible action of maternal IGF-I on fetal growth. Horm Res 1994;42:62–65.
7.
Luthman M, Bremme K, Jonsdottir I, Hall K, Roos P, Werner S: Serum levels and molecular sizes of growth hormone during pregnancy in relation to levels of lactogens, insulin-like growth factor I and insulin-like growth factor binding protein-1. Gynecol Obstet Invest 1991;31:67–73.
8.
Koistinen R, Kalkkinen N, Huhtala ML, Seppälä M, Bohn H, Rutanen EM: Placental protein 12 is a decidual protein that binds somatomedin and has an identical N-terminal amino acid sequence with somatomedin-binding protein from human amniotic fluid. Endocrinology 1986;118:1375–1378.
9.
Westwood M, Gibson JM, Davies AJ, Young RT, White A: The phosphorylation pattern of insulin-like growth factor-binding protein-1 in normal plasma is different from that in amniotic fluid and changes during pregnancy. J Clin Endocrinol Metab 1994;79:1735–1741.
10.
Gargosky SE, Pham HM, Wilson KF, Liu F, Giudice LC, Rosenfeld RG: Measurement and characterization of insulin-like growth factor binding protein-3 in human biological fluids: Discrepancies between radioimmunoassay and ligand blotting. Endocrinology 1992;131:3051–3060.
11.
Lassarre C, Lalou C, Perin L, Binoux M: Protease-induced alteration of insulin-like growth factor binding protein-3 as detected by radioimmunoassay. Agreement with ligand blotting data. Growth Regul 1994;4:48–55.
12.
Lassarre C, Binoux M: Insulin-like growth factor binding protein-3 is functionally altered in pregnancy plasma. Endocrinology 1994;134:1254–1262.
13.
Frystyk J, Dinesen B, Ørskov H: Non-competitive time-resolved immunofluorometric assay for determination of human insulin-like growth factor I and II. Growth Regul 1995;5:169–176.
14.
Frystyk J, Skjærbæk C, Dinesen B, Ørskov H: Free insulin-like growth factors (IGF-I and IGF-II) in human serum. FEBS Lett 1994;348:185–191.
15.
Hossenlopp P, Seurin D, Segovia Quinson B, Hardouin S, Binoux M: Analysis of serum insulin-like growth factor binding proteins using Western blotting: Use of the method for titration of the binding proteins and competitive binding studies. Anal Biochem 1986;154:138-143.
16.
Flyvbjerg A, Kessler U, Dorka B, Funk B, Ørskov H, Kiess W: Transient increase in renal insulin-like growth factor binding proteins during initial kidney hypertrophy in experimental diabetes in rats. Diabetologia 1992;35:589–593.
17.
Frystyk J, Vestbo E, Skjærbæk C, Mogensen CE, Ørskov H: Free insulin-like growth factors in human obesity. Metabolism 1995;44(suppl 4):37–44.
18.
Skjærbæk C, Frystyk J, Kaal A, et al: Circadian variation in serum free and total insulin-like growth factor (IGF)-I and IGF-II in untreated and treated acromegaly and growth hormone deficiency. Clin Endocrinol (Oxf) 2000;52:25–33.
19.
Skjærbæk C, Frystyk J, Ørskov H, et al: Differential changes in free and total insulin-like growth factor I after major, elective abdominal surgery: The possible role of insulin-like growth factor-binding protein-3 proteolysis. J Clin Endocrinol Metab 1998;83:2445–2449.
20.
Hossenlopp P, Segovia B, Lassarre C, Roghani M, Bredon M, Binoux M: Evidence of enzymatic degradation of insulin-like growth factor-binding proteins in the 150K complex during pregnancy. J Clin Endocrinol Metab 1990;71:797–805.
21.
Hasegawa T, Hasegawa Y, Takada M, Tsuchiya Y: The free form of insulin-like growth factor I increases in circulation during normal human pregnancy. J Clin Endocrinol Metab 1995;80:3284–3286.
22.
Suikkari AM, Baxter RC: Insulin-like growth factor-binding protein-3 is functionally normal in pregnancy serum. J Clin Endocrinol Metab 1992;74:177–183.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.