, Volume 12, Issue 2, pp 292–297 | Cite as

Microvessel density and VEGF expression in pituitaries of pregnant women

  • Fabio RotondoEmail author
  • Angelo Rotondo
  • Mark Jentoft
  • Bernd W. Scheithauer
  • Luis V. Syro
  • Jorge H. Donado
  • James E. Tarara
  • Kalman Kovacs
Research paper


OBJECTIVE: In pregnant women, the pituitary is enlarged and the prolactin (PRL) secreting cells increase in size and number. This PRL cell hyperplasia is associated with hyperprolactinemia. The aim of the present work was to investigate adenohypophysial vascularization and immunoexpression of vascular endothelial growth factor (VEGF) in pituitaries of pregnant and post-partum women and compare the results with age-matched adenohypophyses of non-pregnant women who had no endocrine diseases. DESIGN: Pituitaries (n=18) obtained by autopsy from female patients of reproductive age who had died during pregnancy, after abortion or during post-partum were immunostained for CD-34 and VEGF using the streptavidinbiotin-peroxidase complex method. RESULTS: The results showed that microvessel densities and VEGF immunoexpression in the adenohypophyses of pregnant and post-partum women were similar to those found in the control pituitaries. CONCLUSION: It can be concluded that pituitary enlargement and PRL cell hyperplasia in pregnant women may occur without neovascularization and increased VEGF immunoexpression.

Key words

Angiogenesis Immunohistochemistry Pituitary Pregnancy Vascular endothelial growth factor 


  1. 1.
    Scheithauer BW, Sano T, Kovacs KT, Young WF Jr, Ryan N, Randall RV, 1990 The pituitary gland in pregnancy: a clinicopathologic and immunohistochemical study of 69 cases. Mayo Clin Proc 64: 461–474.CrossRefGoogle Scholar
  2. 2.
    Gonzalez JG, Elizondo G, Saldivar D, Nanez H, Todd LE, Villarreal JZ, 1988 Pituitary gland growth during normal pregnancy: an in vivo study using magnetic resonance imaging. Am J Med 85: 217–220.CrossRefGoogle Scholar
  3. 3.
    Goluboff LG, Ezrin C, 1969 Effect of pregnancy on the somatotroph and the prolactin cell of the human adenohypophysis. J Clin Endocrinol Metab 29: 1533–1538.CrossRefGoogle Scholar
  4. 4.
    Friesen HG, Fournier P, Desjardins P, 1973 Pituitary prolactin in pregnancy and normal and abnormal lactation. Clin Obstet Gynecol 16: 25–45.CrossRefGoogle Scholar
  5. 5.
    Erdheim J, Stumme E, 1909 über die Schwangerschaftsveränderung der Hypophyse. Beitr Pathol Anat Allg Pathol 46: 1–132.Google Scholar
  6. 6.
    Aubert ML, Grumbach MM, Kaplan SL, 1974 Heterologous radioimmunoassay for plasma human prolactin (hPRL); values in normal subjects, puberty, pregnancy and pituitary disorders. Acta Endocrinol 77: 460–476.PubMedCrossRefGoogle Scholar
  7. 7.
    Biswas S, Rodeck CH, 1976 Plasma prolactin levels during pregnancy. Br J Obstet Gynaecol 83: 683–687.CrossRefGoogle Scholar
  8. 8.
    Asa SL, Penz G, Kovacs K, Ezrin C, 1982 Prolactin cells in the human pituitary. A quantitative immunocytochemical analysis. Arch Pathol Lab Med 106: 360–363.PubMedGoogle Scholar
  9. 9.
    Stefaneanu L, Kovacs K, Lloyd RV, et al, 1992 Pituitary lactotrophs and somatotrophs in pregnancy: a correlative in situ hybridization and immunocytochemical study. Virchows Archiv B Cell Pathol 62: 291–296.CrossRefGoogle Scholar
  10. 10.
    Erikson L, 1989 Growth hormone in human pregnancy. Maternal 24-hour serum profiles and experimental effects of continuous GH secretion. Acta Obstet Gynecol Scand Suppl 147: 1–38.Google Scholar
  11. 11.
    Rotondo F, Scheithauer BW, Kovacs K, Bell DC, 2009 Rab 3B immunoexpression in human pituitary adenomas. Appl Immunohistochem Mol Morphol 17: 185–188.CrossRefGoogle Scholar
  12. 12.
    Rotondo F, Sharma S, Scheithauer BW, et al, 2010 Endoglin and CD-34 immunoreactivity in the assessment of microvessel density in normal pituitary and adenoma subtypes. Neoplasma 57: 590–593.CrossRefGoogle Scholar
  13. 13.
    Lloyd RV, Scheithauer BW, Kuroki T, Vidal S, Kovacs K, Stefaneanu L, 1999 Vascular endothelial growth factor (VEGF) expression in human pituitary adenomas and carcinomas. Endocr Pathol 10: 229–235.CrossRefGoogle Scholar
  14. 14.
    Folkman J, 1990 What is the evidence that tumors are angiogenesis dependent? J NatL Cancer Inst 82: 4–6.CrossRefGoogle Scholar
  15. 15.
    Denekamp J, 1993 Angiogenesis, neovascular proliferation and vascular pathophysiology as targets for cancer therapy. Br J Radiol 66: 181–196.CrossRefGoogle Scholar
  16. 16.
    Furuya M, Yonemitsu Y, 2008 Cancer neovascularization and proinflammatory microenvironments. Curr Cancer Drug Targets 8: 253–265.CrossRefGoogle Scholar
  17. 17.
    Pang RW, Poon RT, 2006 Clinical implications of angiogenesis in cancers. Vasc Health Risk Manag 2: 97–108.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Eichhorn ME, Kleespies A, Angele MK, Jaunch KW, Bruns CJ, 2007 Angiogenesis in cancer: molecular mechanisms, clinical impact. Langenecks Arch Surg 392: 371–379.CrossRefGoogle Scholar
  19. 19.
    Ribatti D, 2004 The involvement of endothelial progenitor cells in tumor angiogenesis. J Cell Mol Med 8:294–300.CrossRefGoogle Scholar
  20. 20.
    Schatteman GC, Awad O, 2004 Hemangioblasts, angioblasts and adult endothelial cell progenitors. Anat Rec A Discov Mol Cell Evol Biol 276: 13–21.CrossRefGoogle Scholar
  21. 21.
    Dome B, Timar J, Ladanyi A, et al, 2009 Circulating endothelial cells, bone-marrow-derived endothelial progenitor cells and proangiogenic hematopoietic cells in cancer: from biology to therapy. Crit Rev Oncol Hematol 69: 108–124.CrossRefGoogle Scholar
  22. 22.
    Bussolino F, Mantovani A, Persico G, 1997 Molecular mechanisms of blood vessel formation. Trends Biochem Sci 22: 251–256.CrossRefGoogle Scholar
  23. 23.
    Risau W. Mechanisms of angiogenesis. Nature 386: 671–674.Google Scholar
  24. 24.
    Hiraoka N, Allen E, Apel IJ, Gyetko MR, Weiss SJ, 1998 Matrix metalloproteinases regulate neovascularization by acting as pericellular fibrinolysins. Cell 95: 365–377.CrossRefGoogle Scholar
  25. 25.
    D’Amato RJ, Loughnan MS, Flynn E, Folkman J, 1994 Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci USA 91: 4082–4085.CrossRefGoogle Scholar
  26. 26.
    Bouck N, Stellmach V, Hsu SC, 1996 How tumors become angiogenic. Adv. Cancer Res 69: 135–174.CrossRefGoogle Scholar
  27. 27.
    Neufeld G, Cohen T, Gengnnovitch S, Poltorak Z, 1999 Vascular endothelial growth factor (VEGF) and its receptors. FASEB J 13: 9–22.CrossRefGoogle Scholar
  28. 28.
    Dvorak HF, 2002 Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. J Clin Oncol 20: 4368–4380.CrossRefGoogle Scholar
  29. 29.
    Ferrara N, Houck K, Jakeman L, Leung DW, 1992 Molecular and biological properties of the vascular endothelial growth factor family of proteins. Endocrine Rev 13: 18–32.CrossRefGoogle Scholar
  30. 30.
    Das R, Vonderhaar BK, 1997 Prolactin as a mitogen in mammary cells. J Mammary Gland Biol Neoplasia 2: 29–39.CrossRefGoogle Scholar
  31. 31.
    Clevenger CV, Furth PA, Hankinson SE, Schuler LA, 2003 Role of prolactin in mammary carcinoma. Endocr Rev 24: 1–27.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Clapp C, Lopez-Gomez FJ, Nava G, et al, 1998 Expression of prolactin mRNA and of prolactin-like proteins in endothelial cells: Evidence for autocrine effects. J Endocrinol 158: 137–144.CrossRefGoogle Scholar
  33. 33.
    Tabruyn SP, Nguyen NQ, Cornet AM, Martial JA, Struman I, 2005 The antiangiogenic factor, 16-kDa human prolactin, induces endothelial cell cycle arrest by acting at both the G0-G1 and the G2-M phases. Mol Endocrinol 19: 1932–1942.CrossRefGoogle Scholar
  34. 34.
    Lloyd RV, Vidal S, Horvath E, Kovacs K, Scheithauer BW, 2003 Angiogenesis in normal and neoplastic pituitary tissues. Microsc Res Tech 60: 244–250.CrossRefGoogle Scholar
  35. 35.
    Vidal S, Scheithauer BW, Kovacs K, 2000 Vascularity in nontumorous human pituitaries and incidental microadenomas: a morphometric study. Endocr Pathol 11: 215–227.CrossRefGoogle Scholar
  36. 36.
    Hickey MM, Simon MC, 2006 Regulation of angiogenesis by hypoxia and hypoxia-inducible factors. Curr Top Dev Biol 76: 217–257.CrossRefGoogle Scholar

Copyright information

© Hellenic Endocrine Society 2013

Authors and Affiliations

  • Fabio Rotondo
    • 1
    Email author
  • Angelo Rotondo
    • 1
  • Mark Jentoft
    • 2
  • Bernd W. Scheithauer
    • 2
  • Luis V. Syro
    • 3
  • Jorge H. Donado
    • 4
  • James E. Tarara
    • 5
  • Kalman Kovacs
    • 1
  1. 1.Department of Laboratory Medicine, Division of Pathology, St. Michael’s HospitalUniversity of TorontoTorontoCanada
  2. 2.Department of PathologyMayo ClinicRochesterUSA
  3. 3.Department of NeurosurgeryHospital Pablo Tobon Uribe and Clinica MedellinMedellinColombia
  4. 4.Clinical EpidemiologyHospital Pablo Tobon Uribe and Universidad Pontificia BolivarianaMedellinColombia
  5. 5.Department of Biochemistry and Molecular BiologyMayo ClinicRochesterUSA

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