Skip to main content
SpringerLink
Log in

Basic fibroblast growth factor expression by two prolactin and thyrotropin-producing pituitary adenomas

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

Abstract

We investigated the expression of basic fibroblast growth factor (bFGF) in an aggressive type of PRL and TSH-producing pituitary adenoma. Immunocytochemistry and electron microscopy were used to characterize the tumors removed from two patients. Immunoassays were used to measure hormone and bFGF levels in vitro and in vivo. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect bFGF mRNA expression by these tumors. Morphologically, these tumors were characterized by an unusual plurihornal pattern with expression of PRL and TSH and the ultrastructural characteristics of the silent subtype 3 adenoma; in addition, both adenomas displayed marked interstitial fibrosis. bFGF was measurable in the circulation of these patients ranging from 7.5–20.5 pg/mL (normal<1 pg/mL). bFGF concentrations were reduced following surgical adenomectomy. bFGF in culture media was present in concentrations of 197–387 pg/24h/105 cells. bFGF mRNA expression was identified in both adenomas examined. bFGF levels were unaltered in the culture media and in the serum of patients following GnRH and TRH treatment. In conclusion, the expression of bFGF by these plurihormonal pituitary adenomas suggests the possiblity that it may play a role in the development of fibrosis and tumor cell proliferation of this unusual type of pituitary neoplasm.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Kovacs K, Horvath E. Tumors of the pituitary gland. Atlas of tumor pathology. Fascicle 21, 2nd ser. Washington, DC: Armed Forces Institute of Pathology, 1986.

    Google Scholar 

  2. Kovacs K, Horvath E, Asa SL, Stefaneanu L, Sano T. Pituitary cells producing more than one hormone. Human pituitary adenomas. Trends Endocrinol Metab 1:104–107, 1989.

    Article  PubMed  CAS  Google Scholar 

  3. Horvath E, Kovacs K. The adenohypophysis. In: Kovacs K, Asa SL, eds. Functional endocrine pathology. Boston, MA: Blackwell Scientific Publications, 1991; 245–281.

    Google Scholar 

  4. Ingraham HA, Albert VR, Chen R, Crenshaw EB III, Elsholtz HP, He X, Kapiloff MS, Mangalam HJ, Swanson LW, Treacy MN, Rosenfeld MG. A family of POU-domain and Pit-1 tissue-specific transcription factors in pituitary and neuroendocrine development. Annu Rev Physiol 52:773–791, 1990.

    Article  PubMed  CAS  Google Scholar 

  5. Horvath E, Kovacs K, Smyth HS, Killinger DW, Scheithauer BW, Randall R, Laws ER Jr, Singer W. A novel type of pituitary adenoma: morphological feature and clinical correlations. J Clin Endocrinol Metab 66:1111–1118, 1988.

    PubMed  CAS  Google Scholar 

  6. Abraham JA, Whang JL, Tumolo A, Mergia A, Friedman J, Gospodarowicz D, Fiddes JC. Human basic fibroblast growth factor: nucleotide sequence and genomic organization. EMBO J 5:2523–2528, 1986.

    PubMed  CAS  Google Scholar 

  7. Ng S-Y, Gunning P, Eddy R, Ponte P, Leavitt J, Shows T, Kedes L. Evolution of the functional human β-actin gene and its multipseudogene family: conservation of noncoding regions and chromosomal dispersion of pseudogenes. Mol Cell Biol 5:2720–2732, 1985.

    PubMed  CAS  Google Scholar 

  8. Reichlin S. Pathogenesis of pituitary tumors. In: Faglia G, Beck-Peccoz P, Ambrosi B, Travaglini P, Spada A, eds. Pituitary adenomas: new trends in basic and clinical research. Amsterdam: Elsevier, 1991; 113–121.

    Google Scholar 

  9. Ezzat S, Melmed S. The role of growth factors in the pituitary. J Endocrinol Invest 13:691–698, 1990.

    PubMed  CAS  Google Scholar 

  10. Gospodarowicz D, Ferrara N, Schweigerer L, Neufeld G. Structural characterization and biological functions of fibroblast growth factor. Endocr Rev 8:95–114, 1987.

    PubMed  CAS  Google Scholar 

  11. Gospodarowicz D, Cheng J, Lui G-M, Baird A, Böhlent P. Isolation of brain fibroblast growth factor by heparin-Sepharose affinity chromatography: identity with pituitary fibroblast growth factor. Proc Natl Acad Sci USA 81:6963–6967, 1984.

    Article  PubMed  CAS  Google Scholar 

  12. Silverlight JJ, Prysor-Jones RA, Jenkins JS. Basic fibroblast growth factor in human pituitary tumours. Clin Endocrinol 32:669–676, 1990.

    CAS  Google Scholar 

  13. Li Y, Koga M, Kasayama S, Matsumoto K, Arita N, Hayakawa T, Sato B. Identification and characterization of high molecular weight forms of basic fibroblast growth factor in human pituitary adenomas. J Clin Endocrinol Metab 75:1436–1441, 1992.

    Article  PubMed  CAS  Google Scholar 

  14. Hughes SE, Hall PA. Immunolocalization of fibroblast growth factor receptor 1 and its ligands in human tissues. Lab Invest 69:173–182, 1993.

    PubMed  CAS  Google Scholar 

  15. Biswas SB, Hammond RW, Anderson LD. Fibroblast growth factors from bovine pituitary and human placenta and their functions in the maturation of porcine granulosa cellsin vitro. Endocrinology 123:559–566, 1988.

    PubMed  CAS  Google Scholar 

  16. Grothe C, Unsicker K. Immunocytochemical localization of basic fibroblast growth factor in bovine adrenal gland, ovary, and pituitary. J Histochem Cytochem 37:1877–1883, 1989.

    PubMed  CAS  Google Scholar 

  17. Baird A, Morméde P, Ying S-Y, Wehrenberg WB, Ueno N, Ling N, Guillemin R. A nonmitogenic pituitary function of fibroblast growth factor: regulation of thyrotropin and prolactin secretion. Proc Natl Acad Sci USA 82:5545–5549, 1985.

    Article  PubMed  CAS  Google Scholar 

  18. Larson GH, Koos RD, Sortino MA, Wise PM. Acute effect of basic fibroblast growth factor on secretion of prolactin as assessed by the reverse hemolytic plaque assay. Endocrinology 126:927–932, 1990.

    Article  PubMed  CAS  Google Scholar 

  19. Atkin SL, Landolt AM, Jeffreys RV, Diver M, Radcliffe J, White MC. Basic fibroblastic growth factor stimulates prolactin secretion from human anterior pituitary adenomas without affecting adenoma cell proliferation. J Clin Endocrinol Metab 77:831–837, 1993.

    Article  PubMed  CAS  Google Scholar 

  20. Prysor-Jones RA, Silverlight JJ, Jenkins JS. Oestradiol, vasoactive intestinal peptide and fibroblast growth factor in the growth of human pituitary tumour cellsin vitro. J Endocrinol 120:171–177, 1989.

    PubMed  CAS  Google Scholar 

  21. Elias KA, Weiner RI. Direct arterial vascularization of estrogen-induced prolactin-secreting anterior pituitary tumors. Proc Natl Acad Sci USA 81:4549–4553, 1984.

    Article  PubMed  CAS  Google Scholar 

  22. Gonsky R, Herman V, Melmed S, Fagin J. Transforming DNA sequences present in human prolactin-secreting pituitary tumors. Mol Endocrinol 5:1687–1695, 1991.

    PubMed  CAS  Google Scholar 

  23. Zimering MB, Katsumata N, Sato Y, Brandi ML, Aurbach GD, Marx SJ, Friesen HG. Increased basic fibroblast growth factor in plasma from multiple endocrine neoplasia type 1: relation to pituitary tumor. J Clin Endocrinol Metab 76:1182–1187, 1993.

    Article  PubMed  CAS  Google Scholar 

  24. Weiner RI, Windle J, Mellon P, Schechter J. Role of FGF in tumorigenesis of the anterior pituitary. J Endocrinol Invest 14(Suppl.):S13, 1991.

    Google Scholar 

  25. Inoue K, Sakai T, Hattori M. The cell-adhesive effect of basic fibroblast growth factor on pituitary cellsin vitro. J Endocrinol 130:381–386, 1991.

    Article  PubMed  CAS  Google Scholar 

  26. Ezzat S, Smyth HS, Ramyar L, Asa SL. Heterogenous in vivo and in vitro expression of basic fibroblast growth factor in human sporadic pituitary adenomas. J Clin Endocrinol Metab 1995; in press.

  27. Asa SL, Scheithauer BW, Bilbao JM, Horvath E, Ryan N, Kovacs K, Randall RV, Laws ER Jr, Singer W, Linfoot JA, Thorner MO, Vale W. A case for hypothalamic acromegaly: a clinicopathological study of six patients with hypothalamic gangliocytomas producing growth hormone-releasing factor. J Clin Endocrinol Metab 58:796–803, 1984.

    PubMed  CAS  Google Scholar 

  28. Zimmerman D, Young WF Jr, Ebersold MJ, Scheithauer BW, Kovacs K, Horvath E, Whitaker MD, Eberhardt NL, Downs TR, Frohman LA. Congenital gigantism due to growth hormone-releasing hormone excess and pituitary hyperplasia with adenomatous transformation. J Clin Endocrinol Metab 76:216–222, 1993.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Endocrinology & Metabolism, University of Toronto, Toronto, Ontario

    Shereen Ezzat MD & William Singer MD

  2. Department of Pathology, University of Toronto, Toronto, Ontario

    Eva Horvath PhD, Kalman Kovacs MD, PhD & Sylvia L. Asa MD, PhD

  3. Department of Neurosurgery, University of Toronto, Toronto, Ontario

    Harley S. Smyth MD

Authors
  1. Shereen Ezzat MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eva Horvath PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kalman Kovacs MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Harley S. Smyth MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. William Singer MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sylvia L. Asa MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ezzat, S., Horvath, E., Kovacs, K. et al. Basic fibroblast growth factor expression by two prolactin and thyrotropin-producing pituitary adenomas. Endocr Pathol 6, 125–134 (1995). https://doi.org/10.1007/BF02739875

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02739875

Key Words

Search

Navigation