Skip to main content
Log in

Immunohistochemical detection of glycoprotein hormone alpha subunit in somatoprolactinic and pure somatotroph adenomas

  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Glycoprotein hormone alpha subunit (αSU) is expressed in nearly all thyreotroph adenomas and most gonadotrophinomas, but is less well documented in plurisecreting adenomas. We therefore examined the immunohistochemical (IHC) expression of αSU in a generally accepted model of plurisecreting adenomas (somatoprolactinic type) by comparison to a series of pure monosecreting somatotroph tumors. Fifty patients (32 females, 18 males) aged 15 to 68 years with clinical and/or biological acromegaly requiring adenomectomy were studied. Forty-five had clinical acromegaly and 5 had isolated amenorrhea and/or galactorrhea syndromes. Forty-eight of the 49 patients who had baseline assessments of plasma GH had a mean concentration of 5 ng/ml or more (normal value <5). Fifteen of the 46 patients who had baseline measurements of plasma PRL had a prolactinemia value greater than 20 ng/ml (normal value <20) but below 100 ng/ml, except for one patient. All the adenomas studied were positive by GH immunohistochemistry; 21 were immunostained by an antiPRL antibody and formed the “somatoprolactinic” (GH-PRL) group. Five of these 21 patients were male. The 12 female patients younger than 50 years had amenorrhea or galactorrhea, and one male patient complained of impotence. Eleven patients (9 females, 2 males) in this GH-PRL group had hyperprolactinemia. Sixteen of these GH-PRL adenomas were immunolabeled by aSU antiserum. The remaining 29 adenomas, which were immunonegative with the PRL antibody and formed the “somatotroph adenoma” (GH) group, were more frequent in male patients (13/29; 45%) compared to GH-PRL group. Eight amenorrhea or galactorrhea syndromes occurred among the 14 women younger than 50 years, 3 of whom had hyperprolactinemia. Thirteen of these 29 adenomas (45%) were immunopositive with αSU antibody. Compared to the GH group, the GH-PRL group had a significant higher frequency of amenorrhea and/or galactorrhea syndromes among women under 50 years (100% vs 57%; p<0.01), as well as hyperprolactinemia (55% vs 15%; p<0.01) and positive aSU immunoreactivity (76% vs 45%; p<0.05). The frequency of extrasellar macroadenomas was not different according to PRL or αSU immunoreactivity. Thus, in this series of somatoprolactinic adenomas, αSU immunopositivity was slightly more frequent than in a control group of pure somatotroph adenomas. Moreover, hyperprolactinemia was more frequent in patients with GH-PRL adenomas, although the size of the pure and mixed adenomas was not different. These results suggest that hyperprolactinemia and/or αSU immunopositivity are more often associated with mixed GH-PRL adenomas.

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. Scheithauer B.W., Horvath E., Kovacs K., Laws E.R., Randall R.V., Ryan N. Plurihormonal pituitary adenomas. Semin. Diagn. Pathol. 3: 69, 1986.

    PubMed  CAS  Google Scholar 

  2. Monson J.P. Multiple hormone production by pituitary tumours. Clin. Endocrinol. (Oxf.) 40: 279, 1994.

    Article  CAS  Google Scholar 

  3. Faglia G. Glycoprotein hormones and pituitary adenomas. Eur. J. Endocrinol. 133; 23, 1995.

    Article  PubMed  CAS  Google Scholar 

  4. Corenblum B., Sirek A.M.T., Horvath E., Kovacs K., Ezrin C. Human mixed somatotrophic and lactotrophic pituitary adenomas. J. Clin. Endocrinol. Metab. 42: 857, 1991.

    Article  Google Scholar 

  5. Horvath E., Kovacks K., Singer W., Ezrin C., Kerenyi N.A. Acidophil stem cell adenoma of the human pituitary. Arch. Pathol. Lab. Med. 101: 594, 1977.

    PubMed  CAS  Google Scholar 

  6. Horvath E., Kovacs K., Singer W., Smyth H.S., Killinger D.W., Ezrin C., Weiss M.H. Acidophil stem cell adenoma of the human pituitary: clinicopathologic analysis of 15 cases. Cancer 47: 761, 1981.

    Article  PubMed  CAS  Google Scholar 

  7. Horvath E., Kovacs K., Scheithauer B.W., Randall R.V., Laws E.R., Thorner M.O., Tindall G.T., Barrow D.L. Pituitary adenomas producing growth hormone, prolactin and one or more glycoprotein hormones: a histologic, immunohistochemical and ultrastructural study of four surgically removed pituitary tumours. Ultrastruct. Pathol. 5; 171, 1983.

    Article  PubMed  CAS  Google Scholar 

  8. Felix I.A., Horvath E., Kovacs K., Smyth H.S., Killinger D.W., Vale J. Mammosomatotroph adenoma of the pituitary associated with gigantism and hyperprolactinemia. A morphological study including immunoelectron microscopy. Acta Neuropathol. (Berl.) 71: 76, 1986.

    Article  CAS  Google Scholar 

  9. Landolt A.M., Heitz P.U. Alpha subunit-producing pituitary adenomas: immunocytochemical and ultrastructural studies. Virchows Arch. A. 409: 417, 1986.

    Article  CAS  Google Scholar 

  10. Zurschmiede C., Landolt A. Distribution of growth hormone and prolactin in secretory granules of the normal and neoplastic human adenohypophysis. Virchows Arch. B. Cell. Pathol. 53: 308, 1987.

    Article  CAS  Google Scholar 

  11. Beckers A., Courtoy R., Stevenaert A., Boniver J., Closset J., Frankenne F., Reznik M., Hennen G. Mammosomatotropes in human pituitary adenomas as revealed by electron microscopic double gold immunostaining method. Acta Endocrinol. (Copenh.) 118; 503, 1988.

    CAS  Google Scholar 

  12. Guyda H., Fobert F., Colle E., Hardy J. Histologic, ultrastructural, and hormonal characterization of a pituitary tumor secreting both hGH and prolactin. J. Clin. Endocrinol. Metab. 36: 531, 1973.

    Article  PubMed  CAS  Google Scholar 

  13. Kanie N., Kageyama N., Kuwayama A., Nakane T., Watanabe M., Kawaoi A. Pituitary adenomas in acromegalic patients: an immunohistochemical and endocrinological study with special reference to prolactin-secreting adenomas. J. Clin. Endocrinol. Metab. 57: 1093, 1983.

    Article  PubMed  CAS  Google Scholar 

  14. Ishibashi M., Yamaji T., Takaku F., Teramoto A., Fukushima T. Secretion of glycoprotein hormone α-subunit by pituitary tumors. J. Clin. Endocrinol. Metab. 64: 1187, 1987.

    Article  PubMed  CAS  Google Scholar 

  15. Asa S.L., Kovacs K., Horvath E., Singer W. Hormone secretion in vitro by plurihormonal pituitary adenomas of the acidophil cell line. J. Clin. Endocrinol. Metab. 75: 68, 1992.

    PubMed  CAS  Google Scholar 

  16. Thapar K., Kovacs K., Lews E.R. The classification and molecular biology of pituitary adenomas. Adv. Tech. Stand. Neurosurg. 22: 4, 1995.

    Google Scholar 

  17. Saccomanno K., Bassetti M., Lania A., Losa M., Faglia G., Spada A. Immunodetection of glycoprotein hormone subunits in nonfunctioning and glycoprotein hormone-secreting pituitary adenomas. J. Endocrinol. Invest. 20: 59, 1997.

    Article  PubMed  CAS  Google Scholar 

  18. Hardy J., Vezina J.L. Transphenoidal neurosurgery of intracranial neoplasm. In: Thompson R.A., Gree J.R. (eds.), Advances in Neurology. Raven New York, Press, 1976 p. 261.

  19. Harris P.E., Alexander J.M., Bikkal H.A., Hsu D.W., Hedley-Whyte E.T., Klibanski A., Jameson J.L. Glycoprotein hormone alpha-subunit production in somatotroph adenomas with and without Gs alpha mutations. J. Clin. Endocrinol. Metab. 75: 918, 1992.

    PubMed  CAS  Google Scholar 

  20. Tourniaire J., Trouillas J., Chalendra D., Bonneton-Emptoz A., Goutelle A., Girod C. Somatotropic adenomas manifested by galactorrhea without acromegaly. J. Clin. Endocrinol. Metab. 61: 451, 1985.

    Article  PubMed  CAS  Google Scholar 

  21. Horvath E., Kovacs K., Killinger D.W., Smyth H., Weiss M.H., Ezrin C. Mammosomatotroph cell adenoma of the human pituitary: A morphologic entity. Virchows Arch. Pathol. Anat. 398: 277, 1983.

    Article  CAS  Google Scholar 

  22. Beck-Peccoz P., Bassetti M., Spada A., Medri G., Arosio M., Giannattasio G., Faglia G. Glycoprotein hormone α-subunit response to growth hormone (GH) — releasing hormone in patients with active acromegaly. Evidence for α-subunit and GH coexistence in the same tumoral cell. J. Clin. Endocrinol. Metab. 61; 541, 1985.

    Article  PubMed  CAS  Google Scholar 

  23. Loras B., Trouillas J., Li H., Durand A., Girod C., Berrand J. Glycoprotein hormone α-Subunit secretion by human pituitary adenomas in patients with acromegaly. Adv. Biosciences 69; 207, 1988.

    Google Scholar 

  24. Kontogeorgos G., Kovacs K., Scheithauer B., Rologis D., Orphanidis G. α-Subunit immunoreactivity in plurihormonal pituitary adenomas of patients with acromegaly. Mod. Pathol. 4: 191, 1991.

    PubMed  CAS  Google Scholar 

  25. Osamura R.Y., Watanabe K. Immunohistochemical colocalization of growth hormone (GH) and α-subunit in human GH secreting pituitary adenomas. Virchows Arch. A. 411: 323, 1987.

    Article  CAS  Google Scholar 

  26. Inada K., Oda K., Utsunomiya H., Itoh J., Osamura Y. Immunohistochemical analysis of GH-producing adenomas with special emphasis on plurihormonality of individual tumor cells by double staining. Tokai J. Exp. and Clin. Med. 17: 213, 1992.

    CAS  Google Scholar 

  27. Kameya T. Plurihormonal adenomas. Pathol. Res. Pract. 187: 574, 1991.

    Article  PubMed  CAS  Google Scholar 

  28. Hietz P.U., Kasper M., Kloppel G., Polak J.M., Vaitukaitis J.L. Glycoprotein hormone alpha-chain production by pancreatic endocrine tumours: a specific marker for malignancy: immunohistochemical analysis of tumors by 155 patients. Cancer 51: 277, 1983.

    Article  Google Scholar 

  29. Russchoff J., Willemer S., Brunzel M., Trautmann M.E., Frank M., Arnold R., Kloppel G. Nucleolar organizer regions and glycoprotein hormone alpha-chain reaction as markers of malignancy in endocrine tumours of the pancreas. Histopathology 22: 51, 1993.

    Article  Google Scholar 

  30. Grossmann M., Trautmann M.E., Poertl S., Hoermann R., Berger P., Arnold R., Mann K. Alpha-subunit and human chorionic gonadotropin β immunoreactivity in patients with malignant endocrine gastroenteropancreatic tumours. Eur. J. Clin. Invest. 24: 131, 1994.

    Article  PubMed  CAS  Google Scholar 

  31. Bando H., Sano T., Ohshima T., Zhang C.Y., Yamasaki R., Matsumoto K., Saito S. Differences in pathological findings and growth hormone responses in patients with growth hormone-producing pituitary adenomas. Endocrinol. Jpn. 39: 355, 1992.

    Article  PubMed  CAS  Google Scholar 

  32. Yamada S., Aiba T., Sano T., Kovacs K., Shishiba Y., Sawano S., Takada K. Growth hormone-producing pituitary adenomas: correlations between clinical characteristics and morphology. Neurosurgery 33: 20, 1993.

    Article  PubMed  CAS  Google Scholar 

  33. Warnet A., Porsova-Dutoit I., Lahlou N., Seret-Begue D., Lajeunie E., Chanson P., Woimant F., Lot G., Guilllausseau P.J., Roger M. Glycoprotein hormone alpha-subunit secretion in prolactinomas and in non-functioning adenomas: relation with the tumour size. Clin. Endocrinol. (Oxf.) 41: 177, 1994.

    Article  CAS  Google Scholar 

  34. Foubert L., Vialatour M., Kujas M., Racadot J., Van Effenterre R., Turpin G. Caractéristiques évolutives des adénomes hypophysaires somatotropes en fonction de leurs caractères immunocytochimiques. Ann. Endocrinol. 56: 297, 1994 (abstract).

    Google Scholar 

  35. Begeot M., Hemming F.J., Dubois P.M. Induction of pituitary lactotrope differentiation by luteinizing hormone a subunit. Science 226: 566, 1984.

    Article  PubMed  CAS  Google Scholar 

  36. Blithe D.L., Richards R.G., Skarules M.C. Free alpha molecules from pregnancy stimulate secretion of prolactin from human decidual cells: a novel function for free alpha in pregnancy. Endocrinology 129: 2257, 1991.

    Article  PubMed  CAS  Google Scholar 

  37. Furuhata S., Kameya T., Tsuruta T., Naritaka H., Toya O.S. Colocalization of growth hormone (GH) and glycoprotein subunit alpha in GH-producing pituitary adenomas in acromegalic patients. Acta Neuropathol. (Berl.) 87: 568, 1994.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vantyghem, M.C., Cortet, C., Bauters, C. et al. Immunohistochemical detection of glycoprotein hormone alpha subunit in somatoprolactinic and pure somatotroph adenomas. J Endocrinol Invest 21, 434–440 (1998). https://doi.org/10.1007/BF03347322

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03347322

Key-words

Navigation