Startseite Differential proteolysis of insulin-like growth factor binding protein-1 (IGFBP-1) in pregnancy
Artikel
Lizenziert
Nicht lizenziert Erfordert eine Authentifizierung

Differential proteolysis of insulin-like growth factor binding protein-1 (IGFBP-1) in pregnancy

  • Frank A. Hills EMAIL logo , Ray K. Iles und Mark H. Sullivan
Veröffentlicht/Copyright: 19. November 2012

Abstract

The insulin-like growth factors and their binding proteins are important for placental and foetal growth. In this study, we have investigated the presence of proteolytic activity directed against insulin-like growth factor binding protein-1 (IGFBP-1) in pregnancy. In addition, the effect of protease activity on IGFBP-1 immunoreactivity and IGF binding was characterised. 125I-IGFBP-1 was incubated with maternal and foetal serum, amniotic fluid and placental extracts. Breakdown of 125I-IGFBP-1 was determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and autoradiography. The size distribution of endogenous IGFBP-1 was determined by Western immunoblotting. Protease inhibitor studies characterised the proteolytic activity, and Western ligand blotting with 125I-IGF-I was used to determine IGF binding capacity of proteolysed IGFBP-1. Amniotic fluid samples collected after labour onset contained proteolytic activity that generated 12- and 19-kDa IGFBP-1 fragments that did not bind to 125I-IGF-I. This activity was not detected in amniotic fluid collected prior to labour onset or in other tissues. Activity was blocked by aprotinin, leupeptin, phenyl methyl sulphonyl fluoride, and Kunitz soybean trypsin inhibitor but not by ethylene diamine tetraacetic acid or pepstatin. Incubation of IGFBP-1 with trypsin generated fragments of a similar size to the amniotic fluid protease. In conclusion, we have demonstrated the presence in vivo of a trypsin-like proteolytic activity that alters the IGF-binding function of IGFBP-1 in pregnancy.


Corresponding author: Frank A. Hills, Department of Natural Sciences Middlesex University, The Burroughs London NW4 4BT, UK, Tel.: +44 20 84115726

The authors stated that there are no conflicts of interest regarding the publication of this article.

We are grateful to SPARKS for financial support of this project.

References

[1] Anime-Nyame N, Hills FA, Sooranna SR, Steer PJ, Johnson MR. A longitudinal study of maternal plasma insulin-like growth factor binding protein-1 concentrations during normal pregnancy and pregnancies complicated by pre-eclampsia. Hum Reprod. 2000;15: 2215–9.10.1093/humrep/15.10.2215Suche in Google Scholar

[2] Bunn RC, Fowlkes JL. Insulin-like growth factor binding protein proteolysis. Trends Endocrinol Metab. 2003;14:176–81.10.1016/S1043-2760(03)00049-3Suche in Google Scholar

[3] Chevalier B, Lagarde A, Degrelle H, Belaisch-Allart J, Giraudet P, Gallet JP. Insulin-like growth factor binding protein-1 level in amniotic fluid: correlation with birth weight. Biol Neonate. 1998;73:404–6.10.1159/000014003Suche in Google Scholar PubMed

[4] Claussen M, Zapf J, Braulke T. Proteolysis of insulin-like growth factor binding protein-5 by pregnancy serum and amniotic fluid. Endocrinology. 1994;134:1964–6.10.1210/endo.134.4.7511097Suche in Google Scholar PubMed

[5] Coppock HA, White A, Aplin JD, Westwood M. Matrix metalloprotease-3 and -9 proteolyze insulin-like growth factor-binding protein-1. Biol Reprod. 2004;71:438–43.10.1095/biolreprod.103.023101Suche in Google Scholar PubMed

[6] Davies SC, Holly JMP, Coulson VJ, Cotterill AM, Abdulla AF, Whittacker PG, et al. The presence of cation-dependent proteases for insulin-like growth factor binding proteins (IGFBPs) does not alter the size distribution of insulin-like growth factors in pregnancy. Clin Endocrinol. 1991;34:501–6.10.1111/j.1365-2265.1991.tb00331.xSuche in Google Scholar PubMed

[7] Firth SM, Baxter RC. Cellular actions of the insulin-like growth factor binding proteins. Endocr Rev. 2002;23:824–54.10.1210/er.2001-0033Suche in Google Scholar PubMed

[8] Frost VJ, Macaulay VM, Wass JA, Holly JM. Proteolytic modification of insulin-like growth factor-binding proteins: comparison of conditioned media from human cell lines, circulating proteases and characterized enzymes. J Endocrinol. 1993;138:545–54.10.1677/joe.0.1380545Suche in Google Scholar PubMed

[9] Gibson JM, Aplin JD, White A, Westwood M. Regulation of IGF bioavailability in pregnancy. Mol Hum Reprod. 2001;7:79–87.10.1093/molehr/7.1.79Suche in Google Scholar PubMed

[10] Giudice LC, Farrell EM, Pham H, Lamson G, Rosenfeld RG. Insulin-like growth factor binding proteins in maternal serum throughout gestation and in the peurperium: effects of a pregnancy-associated serum protease activity. J Clin Endocrinol Metab. 1990;71:806–16.10.1210/jcem-71-4-806Suche in Google Scholar PubMed

[11] Giudice LC, Martina NA, Crystal RA, Tazuke S, Druzin M. Insulin-like growth factor binding protein-1 at the maternal-fetal interface and insulin-like growth factor-I, insulin-like growth factor-II, and insulin-like growth factor binding protein-1 in the circulation of women with severe preeclampsia. Am J Obstet Gynecol. 1997;176:751–7.10.1016/S0002-9378(97)70598-2Suche in Google Scholar

[12] Han VKM, Bassett N, Walton J, Challis JR. The expression of insulin-like growth factor (IGF) and IGF binding protein (IGFBP) genes in the human placenta and membranes: evidence for IGF-IGFBP interactions at the feto-maternal interface. J Clin Endocrinol Metab. 1996;81:2680–93.Suche in Google Scholar

[13] Hills FA, English J, Chard T. Circulating levels of IGF-I and IGF binding protein-1 throughout pregnancy: relation to birthweight and maternal weight. J Endocrinol. 1996;148:303–9.10.1677/joe.0.1480303Suche in Google Scholar

[14] Holmes RP, Holly JMP, Soothill PW. Maternal serum insulin-like growth factor binding protein-2 and -3 and fetal growth. Hum Reprod. 1999;14:1479–84.10.1093/humrep/14.7.1879Suche in Google Scholar

[15] Hossenlopp P, Segovia B, Lassarre C, Roghani M, Bredon M, Bionoux M. Evidence of enzymatic degradation of insulin-like growth factor binding proteins in the “150 K” complex during pregnancy. J Clin Endocrinol Metab. 1990;71:797–805.10.1210/jcem-71-4-797Suche in Google Scholar

[16] Hwa V, Oh Y, Rosenfeld RG. The insulin-like growth factor binding protein (IGFBP) superfamily. Endocr Rev. 1999;20:761–87.Suche in Google Scholar

[17] Irwin JC, Suen LF, Cheng BH, Martin R, Cannon P, Deal CL, et al. Human placental trophoblasts secrete a disintegrin metalloproteinase very similar to the insulin-like growth factor binding protein-3 protease in human pregnancy serum. Endocrinology. 2000;141:666–74.10.1210/endo.141.2.7292Suche in Google Scholar

[18] Kalus W, Zweckstetter M, Renner C, Sanchez Y, Georgescu J, Grol M, et al. Structure of the IGF-binding domain of the insulin-like growth factor binding protein-5 (IGFBP-5: implications for IGF and IGF-I receptor interactions). EMBO J. 1998;17:6558–72.10.1093/emboj/17.22.6558Suche in Google Scholar

[19] Kobayashi H, Suzuki K, Sugino D, Terao T. Urinary trypsin inhibitor levels in amniotic fluid of normal human pregnancy: decreased levels observed at parturition. Am J Obstet Gynecol. 1999;180:141–7.10.1016/S0002-9378(99)70164-XSuche in Google Scholar

[20] Lamson G, Giudice LC, Rosenfeld RG. A simple assay for proteolysis of IGFBP-3. J Clin Endocrinol Metab. 1991;72:1391–3.10.1210/jcem-72-6-1391Suche in Google Scholar PubMed

[21] Laroche D, Herlicoviez M, Pasquet C, Travert G, Fernandez Y. Amniotic fluid immunoreactive trypsin in pregnancies with normal and pathological outcomes. Acta Obstet Gynecol Scand. 1987;66:587–90.10.3109/00016348709022061Suche in Google Scholar PubMed

[22] Lassare C, Binoux M. Insulin-like growth factor binding protein-3 is functionally altered during pregnancy. Endocrinology. 1994;134:1254–62.10.1210/endo.134.3.7509737Suche in Google Scholar PubMed

[23] Lee SE, Han BD, Park IS, Romero R, Yoon BH. Evidence supporting proteolytic cleavage of insulin-like growth factor binding protein-1 (IGFBP-1) protein in amniotic fluid. J Perinat Med. 2008;36:316–23.10.1515/JPM.2008.067Suche in Google Scholar

[24] Loechel F, Fox JW, Murphy G, Albrechtsen R, Wewer UM. ADAM 12-S cleaves IGFBP-3 and IGFBP-5 and is inhibited by TIMP-3. Biochem Biophys Res Commun. 2000;278:511–5.10.1006/bbrc.2000.3835Suche in Google Scholar

[25] Maile LA, Holly JMP. Insulin-like growth factor binding protein (IGFBP) proteolysis: occurrence, identification, role and regulation. Growth Horm IGF Res. 1999;9:85–95.10.1054/ghir.1999.0096Suche in Google Scholar

[26] Neumann GM, Bach LA. The N-terminal disulphide linkages of human insulin-like growth factor-binding protein-6 (hIGFBP-6) and hIGFBP-1 are different as determined by mass spectrometry. J Biol Chem. 1999;274:14587–94.10.1074/jbc.274.21.14587Suche in Google Scholar

[27] Nunn SE, Peehl DM, Cohen P. Acid-activated insulin-like growth factor binding protein protease activity of cathepsin D in normal and malignant prostatic epithelial cells and seminal plasma. J Cell Physiol. 1997;171:196–204.10.1002/(SICI)1097-4652(199705)171:2<196::AID-JCP10>3.0.CO;2-CSuche in Google Scholar

[28] Okajima T, Iwashita M, Takeda Y, Sakamoto S, Tanabe T, Yasuda T, et al. Inhibitory effects of insulin-like growth factor (IGF)-binding proteins-1 and -3 on IGF-activated glucose consumption in mouse BALB/c 3T3 fibroblasts. J Endocrinol. 2003;136:457–70.10.1677/joe.0.1360457Suche in Google Scholar

[29] Pocknee RC, Abramovich DR. Origin and levels of trypsin in amniotic fluid throughout pregnancy. Br J Obstet Gynaecol. 1982;89:142–4.10.1111/j.1471-0528.1982.tb04681.xSuche in Google Scholar

[30] Robinson PG, Smith PA, Elliott RB. A simple method for the quantitative determination of stool trypsin and chymotrypsin. Clin Chim Acta. 1975;62:225–9.10.1016/0009-8981(75)90231-4Suche in Google Scholar

[31] Rutanen EM, Karkkainen TH, Lehtovirta J, Uotila JT, Hinkula MK, Hartikainen AL. Evaluation of a rapid strip test for insulin-like growth factor binding protein-1 in the diagnosis of ruptured fetal membranes. Clin Chim Acta. 1996;253:91–101.10.1016/0009-8981(96)80001-ESuche in Google Scholar

[32] Rutanen E-M, Koistinen R, Wahlstrom T, Bohn H, Ranta T, Seppala M. Synthesis of placental protein 12 by human decidua. Endocrinology. 1985;116:1304–9.10.1210/endo-116-4-1304Suche in Google Scholar

[33] Sifakis S, Akolekar R, Kappou D, Mantas N, Nicolaides KH. Maternal serum insulin-like growth factor-binding protein-1 (IGFBP-1) at 11-13 weeks in pre-eclampsia. Prenat Diagn. 2011;31:196–201.10.1002/pd.2682Suche in Google Scholar PubMed

[34] Wang HS, Perry LA, Kanisius J, Iles RK, Holly JMP, Chard T. Purification and assay of insulin-like growth factor binding protein-1: measurement of circulating levels throughout pregnancy. J Endocrinol. 1991;128:161–8.10.1677/joe.0.1280161Suche in Google Scholar PubMed

Received: 2012-4-26
Accepted: 2012-10-16
Published Online: 2012-11-19
Published in Print: 2013-05-01

©2013 by Walter de Gruyter Berlin Boston

Artikel in diesem Heft

  1. Masthead
  2. Masthead
  3. Review
  4. The diagnosis of rupture of fetal membranes (ROM): a meta-analysis
  5. Original Articles – Obstetrics
  6. Differential proteolysis of insulin-like growth factor binding protein-1 (IGFBP-1) in pregnancy
  7. Hyperoxic resuscitation after hypoxia-ischemia induces cerebral inflammation that is attenuated by tempol in a reporter mouse model with very young mice
  8. Prenatal maternal stress predicts cord-blood ferritin concentration
  9. Puerperal curettage after cesarean section delivery
  10. Psychological reactions related to fetal magnetic resonance imaging: a follow-up study
  11. Ethnic disparity in amniotic fluid levels of hyaluronan, histone H2B and superoxide dismutase in spontaneous preterm birth
  12. Mode of delivery in a subsequent pregnancy following previous instrumental delivery
  13. Original Articles – Fetus
  14. Pregnancy and neonatal outcome following an antenatal diagnosis of cleft lip and palate
  15. Genetic low nephron number hypertension is associated with altered expression of osteopontin and CD44 during nephrogenesis*
  16. Pharmacovigilance in pregnancy: adverse drug reactions associated with fetal disorders
  17. Expectant management in type II selective intrauterine growth restriction and abnormal chord insertion in monochorionic twins
  18. Can prenatal detection of Down syndrome be improved by enhancing obstetricians’ skills of performing adequate foetal cardiac examination at the primary level?a
  19. Original Articles – Newborn
  20. The national perinatal mortality rate in the State of Qatar during 2011; trends since 1990 and comparative analysis with selected high-income countries: The PEARL Study Project*
  21. Determinants of successful breastfeeding initiation in healthy term singletons: a Swiss university hospital observational study
  22. Congress Calendar
  23. Congress Calendar
Heruntergeladen am 13.11.2025 von https://www.degruyterbrill.com/document/doi/10.1515/jpm-2012-0086/html?lang=de
Button zum nach oben scrollen