Skip to main content
Log in

Immunohistochemical localization of the insulinlike growth factor binding protein-1 in female reproductive tissues by monoclonal antibodies

  • Original Article
  • Published:
Endocrine Pathology Aims and scope Submit manuscript

Abstract

Human insulinlike growth factor binding protein-1 (hlGFBP-1) is a secretory protein that modulates the receptor-binding and biological actions of the insulinlike growth factor I (IGF-I). Human endometrium expresses the mRNA for IGFBP-1, and this protein is secreted by the secretory phase and pregnancy endometrium as well as by ovarian granulosa cells in vitro. In this study, we examined the cellular localization of IGFBP-1 in female reproductive tissues by using a purified monoclonal antibody Mab 6303 with an immunoperoxidase technique. Proliferative- and early secretory-phase endometrium as well as all extrauterine tissues except decidualized cells at the implantation site on the ovaries of ovarian pregnancies were negative for IGFBP-1. In midsecretory-phase endometrium, focal staining was first observed in the cytoplasm of glandular epithelial cells, with weaker staining in the stromal cells. In late secretoryphase endometrium, strong immunostaining was observed in predecidualized stromal cells, with weak focal staining remaining in some of the glandular epithelial cells. In early pregnancy, intense staining was detected in the cytoplasm of decidualized stromal cells of zona compacta in each sample, whereas the nondecidualized stromal cells remained unstained. Strong to medium staining was detected simultaneously in the glandular epithelial cells in 70% of the early pregnancy specimens. In term pregnancy, IGFBP-1 was localized in decidual cells of placental bed and decidua parietalis. Immunolocalization of IGFBP-1 to both endometrial epithelial and stromal cells, although only stromal cells express the gene of IGFBP-1 [14], supports the hypothesis of paracrine actions between these cells. The localization of IGFBP-1 to decidualized cells at the extrauterine implantation sites implies its association with decidual differentiation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Adashi EY, Resnick LE, Hernandez ER, May JV, Knecht M, Svoboda ME, van Wyk JJ. Insulin-like growth factor-1 as an amplifier of follicle-stimulating hormone action: studies on mechanism(s) and site(s) of action in cultured rat granulosa cells. Endocrinology 122:1583–1591, 1988.

    Article  CAS  Google Scholar 

  2. Ballard J, Baxter R, Binoux M, Clemmons D, Drop S, Hall K, Hintz R, Rechler M, Rutanen E, Schwander J. On the nomenclature of the IGF binding proteins. Acta Endocrinol (Copenh) 121:751–752, 1989.

    Article  CAS  Google Scholar 

  3. Baxter RC. The somatomedins: insulin-like growth factors. Adv Clin Chem 25:49–115, 1986.

    Article  CAS  Google Scholar 

  4. Baxter RC, Martin JI. Binding proteins for the insulin-like growth factors: structure, regulation and function. Prog Growth Factor Res 1:49–68, 1989.

    Article  CAS  Google Scholar 

  5. Baxter RC, Martin JL, Wood MH. Two immunoreactive binding proteins for insulinlike growth factors in human amniotic fluid: relationship to fetal maturity. J Clin Endocrinol Metab 65:423–431, 1987.

    Article  CAS  Google Scholar 

  6. Bell SC, Smith S. The endometrium as a paracrine organ. In: Chamberlain GVP, ed. Contemporary obstetrics and gynaecology. London: Butterworths, 273–298, 1988.

    Google Scholar 

  7. Bohn H, Kraus W. Isolierung und Charakterisierung eines neuen plazentaspezifischen Proteins (PP12). Arch Gynecol 229:279–291, 1980.

    Article  CAS  Google Scholar 

  8. Brewer MT, Stetler GL, Squires CH, Thompson RC, Busby WH, Clemmons DR. Cloning, characterization, and expression of a human insulin-like growth factor binding protein. Biochem Biophys Res Commun 152:1289–1297, 1988.

    Article  CAS  Google Scholar 

  9. Brinkman A, Groffen C, Kortleve DJ, Geurts van Kessel A, Drop SLS. Isolation and characterization of a cDNA encoding the low molecular weight insulin-like growth factor binding protein (IBP-1). EMBO J 7:2417–2423, 1988.

    Article  CAS  Google Scholar 

  10. Busby WH Jr, Klapper DG, Clemmons DR. Purification of a 31,000-dalton insulin-like growth factor binding protein from human amniotic fluid. Isolation of two forms with different biologic actions. J Biol Chem 263: 14203–14210, 1988.

    CAS  Google Scholar 

  11. Elgin RG, Busby WH Jr, Clemmons DR. An insulin-like growth factor (IGF) binding protein enhances the biologic response to IGF-I. Proc Natl Acad Sci USA 84:3254–3258, 1987.

    Article  CAS  Google Scholar 

  12. Hill DJ, Clemmons DR, Wilson S, Han VKM, Strain AJ, Milner RDG. Immunological distribution of one form of insulin-like growth factor (IGF)-binding protein and IGF peptides in human fetal tissues. J Mol Endocrinol 2:31–38, 1989.

    Article  CAS  Google Scholar 

  13. Julkunen M, Koistinen R, Aalto-Setälä K, Seppälä M, Jänne OA, Kontula K. Primary structure of human insulin-like growth factorbinding protein placental protein 12 and tissue-specific expression of its mRNA. FEBS Lett 236:295–302, 1988.

    Article  CAS  Google Scholar 

  14. Julkunen M, Koistinen R, Suikkari A-M, Seppälä M, Jänne OA. Identification by hybridization histochemistry of human endometrial cells expressing mRNAs encoding a uterine β-lactoglobulin homologue and insulin-like growth factor-binding protein-1. Mol Endocrinol 4:700–707, 1990.

    Article  CAS  Google Scholar 

  15. Lee Y-L, Hintz RL, James PM, Lee PDK, Shively JE, Powell DR. Insulin-like growth factor (IGF) binding protein complementary deoxyribonucleic acid from human HEP G2 hepatoma cells: predicted protein sequence suggests an IGF binding domain different from those of the IGF-1 and IGF-II receptors. Mol Endocrinol 2:404–411, 1988.

    Article  CAS  Google Scholar 

  16. Lewitt MS, Baxter RC. Regulation of growthhormone-independent insulin-like growth factor-binding protein (BP-28) in cultured human fetal liver explants. J Clin Endocrinol Metab 69:246–252, 1989.

    Article  CAS  Google Scholar 

  17. Novak ER, Woodruff JD. Novak’s gynecologic and obstetric pathology with clinical and endocrine relations. Philadelphia: Saunders, 1974.

    Google Scholar 

  18. Pekonen F, Suikkari A-M, Makinen T, Rutanen E-M. Different insulin-like growth factor binding species in human placenta and decidua. J Clin Endocrinol Metab 67:1250–1257, 1988.

    Article  CAS  Google Scholar 

  19. Povoa G, Enberg G, Jörnvall H, Hall K. Isolation and characterization of a somatomedin-binding protein from mid-term amniotic fluid. EurJ Biochem 144:199–204, 1984.

    Article  CAS  Google Scholar 

  20. Rechler MM, Nissley SP. The nature and regulation of the receptors for insulin-like growth factors. Rev Physiol 47:425–442, 1985.

    Article  CAS  Google Scholar 

  21. Ritvos O, Ranta T, Jalkanen J, Suikkari A-M, Voutilainen R, Bohn H, Rutanen E-M. Insulin-like growth factor (IGF) binding protein from human decidua inhibits the binding and biological action of IGF-I in cultured choriocarcinoma cells. Endocrinology 122:2150–2157, 1988.

    Article  CAS  Google Scholar 

  22. Rutanen E-M, Kärkkäinen T, Lundqvist C, Pekonen F, Ritvos O, Tanner P, Welin M, Weber T. Monoclonal antibodies to the 27-34K insulin-like growth factor binding protein. Biochem Biophys Res Commun 152:208–215, 1988.

    Article  CAS  Google Scholar 

  23. Rutanen E-M, Koistinen R, Sjöberg J, Julkunen M, Wahlstrom T, Bohn H, Seppälä M. Synthesis ot placental protein 12 by human endometrium. Endocrinology 118:1067–1071, 1986.

    Article  CAS  Google Scholar 

  24. Rutanen E-M, Koistinen R, Wahlström T, Bohn H, Ranta T, Seppälä M. Synthesis of placental protein 12 by human decidua. Endocrinology 116:1304–1309, 1985.

    Article  CAS  Google Scholar 

  25. Rutanen E-M, Pekonen F, Mäkinen T. Soluble 34K binding protein inhibits the binding of insulin-like growth factor I to its cell receptors in human secretory phase endometrium: evidence for autocrine/paracrine regulation of growth factor action. J Clin Endocrinol Metab 66:173–180, 1988.

    Article  CAS  Google Scholar 

  26. Suikkari A-M, Jalkanen J, Koistinen R, Butzow R, Ritvos O, Ranta T, Seppälä M. Human granulosa cells synthesize low molecular weight insulin-like growth factor binding protein. Endocrinology 124:1088–1090, 1989.

    Article  CAS  Google Scholar 

  27. Wahlström T, Bohn H, Seppälä M. Immunohistological studies on pregnancy proteins. In: Grudzinskas JG, Teisner B, Seppälä M, eds. Pregnancy proteins: biology, chemistry and clinical applications. Sydney: Academic Press, 415–422, 1982.

    Google Scholar 

  28. Wahlstrom T, Seppälä M. Placental protein 12 (PP12) is induced in the endometrium by progesterone. Fertil Steril 41:781–784, 1984.

    Article  CAS  Google Scholar 

  29. Waites GT, James RFL, Bell SC. Immunohistological localization of the human endometrial secretory protein pregnancy-associated endometrial α1-globulin, an insulin-like growth factor-binding protein during the menstrual cycle. J Clin Endocrinol Metab 67:1100–1104, 1988.

    Article  CAS  Google Scholar 

  30. Waites GT, James RFL, Bell SC. Human ‘pregnancy-associated endometrial α1-globulin’, an insulin-like growth factor-binding protein: immunohistological localization in the decidua and placenta during pregnancy employing monoclonal antibodies. J Endocrinol 120:351–357, 1989.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rutanen, EM., Gonzalez, E., Said, J. et al. Immunohistochemical localization of the insulinlike growth factor binding protein-1 in female reproductive tissues by monoclonal antibodies. Endocr Pathol 2, 132–138 (1991). https://doi.org/10.1007/BF02915453

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02915453

Keywords

Navigation