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Immunonegative null cell″adenomas and Gnadotropin (G) Subunit (Su) immunopositive adenomas share frequent expression of multiple transcription factors

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Abstract

The differentiation of pituitary cells and human pituitary adenomas follow three cell lineages: H-PRTSH, ACTH, and FSHH, which are regulated by a combination of various transcription factors and co-factors. We have used R-PCRand immunohistochemistry to show that immunonegative, null cell″adenomas are equipped with multiple transcription factors and co-factors. The null cell″adenomas showed similar frequencies of transcription factors as did the gonadotropin subunit (GSU)positive adenomas, with the exception that there were fewer instances of SF1 in the former. We speculate, therefore, that null cell adenomas and GSUpositive adenomas share common molecular mechanisms in functional differentiation, even though the former do not produce hormones. From the high frequency of various transcription factors, we also speculate that both null cell adenomas and GSUpositive adenomas are derived from committed″pituitary progenitor stem cells. The questions, why a certain proportion of these pituitary tumor groups lack hormone production and why they are molecularly more committed to G transcription, remain to be further investigated.

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References

  1. Andersen B, Rosenfeld MG. Pit-1 determines cell types during development of the anterior pituitary gland. A model for transcriptional regulation of cell phenotypes in mammalian organogenesis. J Biol Chem 269:29335–29338, 1994.

    PubMed  CAS  Google Scholar 

  2. Asa SL, Bamberger AM, Cao B, Wong M, Parker KL, Ezzat S. The transcription activator steroidogenic factor-1 is preferentially expressed in the human pituitary gonadotroph. J Clin Endocrinol Metab 81:2165–2170, 1996.

    Article  PubMed  CAS  Google Scholar 

  3. Aylwin SJ, Welch JP, Davey CL, et al. The relationship between steroidogenic factor 1 and DAX-1 expression and in vitro gonadotropin secretion in human pituitary adenomas. J Clin Endocrinol Metab 86:2476–2483, 2001.

    Article  PubMed  CAS  Google Scholar 

  4. Dasen JS, O’Connell SM, Flynn SE, et al. Reciprocal interactions of Pit1 and GATA2 mediate signaling gradient-induced determination of pituitary cell types. Cell 97:587–598, 1999.

    Article  PubMed  CAS  Google Scholar 

  5. Gordon DF, Woodmansee WW, Black JN, et al. Domains of Pit-1 required for transcriptional synergy with GATA-2 on the TSH beta gene. Mol Cell Endocrinol 196:53–66, 2002.

    Article  PubMed  CAS  Google Scholar 

  6. Guy JC, Hunter CS, Showalter AD, et al. Conserved amino acid sequences confer nuclear localization upon the Prophet of Pit-1 pituitary transcription factor protein. Gene 336:263–273, 2004.

    Article  PubMed  CAS  Google Scholar 

  7. Haisenleder DJ, Yasin M, Dalkin AC, Gilrain J, Marshall JC. GnRH regulates steroidogenic factor-1 (SF-1) gene expression in the rat pituitary. Endocrinology 137:5719–5722, 1996.

    Article  PubMed  CAS  Google Scholar 

  8. Horvath E, Kovacs K. Pituitary gland. Pathol Res Pract 183:129–142, 1988.

    PubMed  CAS  Google Scholar 

  9. Ikuyama S, Mu YM, Ohe K, et al. Expression of an orphan nuclear receptor DAX-1 in human pituitary adenomas. Clin Endocrinol (Oxf) 48:647–654, 1998.

    Article  CAS  Google Scholar 

  10. Ikuyama S, Ohe K, Sakai Y, et al. Follicle stimulating hormone-beta subunit gene is expressed in parallel with a transcription factor Ad4BP/SF-1 in human pituitary adenomas. Clin Endocrinol (Oxf) 45:187–193, 1996.

    Article  CAS  Google Scholar 

  11. Kovacs K, Horvath E, Ryan N, Ezrin C. Null cell adenoma of the human pituitary. Virchows Arch A Pathol Anat Histol 387:165–174, 1980.

    Article  PubMed  CAS  Google Scholar 

  12. Lamolet B, Pulichino AM, Lamonerie T, et al. A pituitary cell-restricted T box factor, Tpit, activates POMC transcription in cooperation with Pitx homeoproteins. Cell 104:849–859, 2001.

    Article  PubMed  CAS  Google Scholar 

  13. Lloyd RV, Osamura RY. Transcription factors in normal and neoplastic pituitary tissues. Microsc Res Tech 39:168–181, 1997.

    Article  PubMed  CAS  Google Scholar 

  14. Nakamura S, Ohtsuru A, Takamura N, et al. Prop-1 gene expression in human pituitary tumors. J Clin Endocrinol Metab 84:2581–2584, 1999.

    Article  PubMed  CAS  Google Scholar 

  15. Nakamura Y, Usui T, Mizuta H, et al. Characterization of Prophet of Pit-1 gene expression in normal pituitary and pituitary adenomas in humans. J Clin Endocrinol Metab 84:1414–1419, 1999.

    Article  PubMed  CAS  Google Scholar 

  16. Nogami H, Inoue K, Moriya H, et al. Regulation of growth hormone-releasing hormone receptor messenger ribonucleic acid expression by glucocorticoids in MtT-S cells and in the pituitary gland of fetal rats. Endocrinology 140:2763–2770, 1999.

    Article  PubMed  CAS  Google Scholar 

  17. Osamura RY, Tahara S, Komatsubara K, et al. Pit-1 positive alpha-subunit positive nonfunctioning human pituitary adenomas: a dedifferentiated GH cell lineage? Pituitary 1:269–271, 1999.

    Article  PubMed  CAS  Google Scholar 

  18. Osamura RY, Watanabe K. Immunohistochemical studies of human FSH producing pituitary adenomas. Virchows Arch A Pathol Anat Histopathol 413:61–68, 1988.

    Article  PubMed  CAS  Google Scholar 

  19. Oyama K, Sanno N, Teramoto A, Osamura RY. Expression of neuro D1 in human normal pituitaries and pituitary adenomas. Mod Pathol 14:892–899, 2001.

    Article  PubMed  CAS  Google Scholar 

  20. Palomino T, Sanchez Pacheco A, Pena P, Aranda A. A direct protein-protein interaction is involved in the cooperation between thyroid hormone and retinoic acid receptors and the transcription factor GHF-1. FASEB J 12:1201–1209, 1998.

    PubMed  CAS  Google Scholar 

  21. Pulichino AM, Vallette Kasic S, Tsai JP, Couture C, Gauthier Y, Drouin J. Tpit determines alternate fates during pituitary cell differentiation. Genes Dev 17:738–747, 2003.

    Article  PubMed  CAS  Google Scholar 

  22. Sanno N, Jin L, Qian X, et al. Gonadotropin-releasing hormone and gonadotropin-releasing hormone receptor messenger ribonucleic acids expression in nontumorous and neoplastic pituitaries. J Clin Endocrinol Metab 82:1974–1982, 1997.

    Article  PubMed  CAS  Google Scholar 

  23. Sanno N, Teramoto A, Matsuno A, Osamura RY. Expression of human Pit-1 product in the human pituitary and pituitary adenomas. Immunohistochemical studies using an antibody against synthetic human Pit-1 product. Arch Pathol Lab Med 120:73–77, 1996.

    PubMed  CAS  Google Scholar 

  24. Sanno N, Teramoto A, Sugiyama M, et al. Expression of Pit-1 mRNA and activin/inhibin subunits in clinically nonfunctioning pituitary adenomas. In situ hybridization and immunohistochemical analysis. Horm Res 50:11–17, 1998.

    Article  PubMed  CAS  Google Scholar 

  25. Sheng HZ, Moriyama K, Yamashita T, et al. Multistep control of pituitary organogenesis. Science 278:1809–1812, 1997.

    Article  PubMed  CAS  Google Scholar 

  26. Suh H, Gage PJ, Drouin J, Camper SA. Pitx2 is required at multiple stages of pituitary organogenesis: pituitary primordium formation and cell specification. Development 129:329–337, 2002.

    PubMed  CAS  Google Scholar 

  27. Tahara S, Kurotani R, Sanno N, et al. Expression of pituitary homeo box 1 (Ptx1) in human non-neoplastic pituitaries and pituitary adenomas. Mod Pathol 13:1097–1108, 2000.

    Article  PubMed  CAS  Google Scholar 

  28. Tremblay JJ, Goodyer CG, Drouin J. Transcriptional properties of Ptx1 and Ptx2 isoforms. Neuroendocrinology 71:277–286, 2000.

    Article  PubMed  CAS  Google Scholar 

  29. Tremblay JJ, Lanctot C, Drouin J. The panpituitary activator of transcription, Ptx1 (pituitary homeobox 1), acts in synergy with SF-1 and Pit1 and is an upstream regulator of the Lim-homeodomain gene Lim3/Lhx3. Mol Endocrinol 12:428–441, 1998.

    Article  PubMed  CAS  Google Scholar 

  30. Umeoka K, Sanno N, Osamura RY, Teramoto A. Expression of GATA-2 in human pituitary adenomas. Mod Pathol 15:11–17, 2002.

    Article  PubMed  Google Scholar 

  31. Vallette Kasic S, Figarella Branger D, Grino M, et al. Differential regulation of proopiomelanocortin and pituitary-restricted transcription factor (TPIT), a new marker of normal and adenomatous human corticotrophs. J Clin Endocrinol Metab 88:3050–3056, 2003.

    Article  PubMed  CAS  Google Scholar 

  32. West BE, Parker GE, Savage JJ, et al. Regulation of the follicle-stimulating hormone beta gene by the LHX3 LIM-homeodomain transcription factor. Endocrinology 145:4866–4879, 2004.

    Article  PubMed  CAS  Google Scholar 

  33. Zhao D, Tomono Y, Tsuboi K, Nose T. Immunohistochemical and ultrastructural study of clinically nonfunctioning pituitary adenomas. Neurol Med Chir (Tokyo) 40:453–456, discussion 456–457, 2000.

    Article  CAS  Google Scholar 

  34. DeLellis RA, Lloyd RV, Heitz PU, Eng C. WHO classification of tumors. Pathology and genetics of tumors of endocrine organs. Lyon, France: IARC, 2004.

    Google Scholar 

  35. Savage JJ, Yaden BC, Kiratipranon P, Rhodes SJ. Transcriptional control during mammalian anterior pituitary development. Gene 319:1–19, 2003.

    Article  PubMed  CAS  Google Scholar 

  36. Scully KM, Rosenfeld MG. Pituitary development: regulatory codes in mammalian organogenesis. Science 295:2231–2235, 2002.

    Article  PubMed  CAS  Google Scholar 

  37. Shupnik MA, Pitt LK, Soh AY, Anderson A, Lopes MB, Laws ER Jr. Selective expression of estrogen receptor alpha and beta isoforms in human pituitary tumors. J Clin Endocrinol Metab 83:3965–3972, 1998.

    Article  PubMed  CAS  Google Scholar 

  38. Asa SL, Puy LA, Lew AM, Sundmark VC, Elsholts HP. Cell type-specific expression of the pituitary transcription activator pit-1 in the human pituitary and pituitary adenomas. J Clin Endocrinol Metab 77:1275–1280, 1993.

    Article  PubMed  CAS  Google Scholar 

  39. Simmons DM, Voss JW, Ingraham HA, et al. Pituitary cell phenotypes involve cell-specific Pit-1 mRNA translation and synergistic interactions with other classes of transcription factors. Genes Dev 4(5):695–711, 1990.

    PubMed  CAS  Google Scholar 

  40. Ikeda Y, Lala DS, Luo X, Kim E, Moisan MP, Parker KL. Characterization of the mouse FTZ-F1 gene, which encodes a key regulator of steroid hydroxylase gene expression. Mol Endocrinol 7(7):852–860, 1993.

    Article  PubMed  CAS  Google Scholar 

  41. Morohashi K, Iida H, Nomura M, et al. Functional difference between Ad4BP and ELP, and their distributions in steroidogenic tissues. Mol Endocrinol 8(5):643–653, 1994.

    Article  PubMed  CAS  Google Scholar 

  42. Naya FJ, Stellrecht CM, Tsai Mj. Tissue-specific regulation of the insulin gene by a novel basic helix-loop-helix transcription factor. Genes Dev 9(8):1009–1019, 1995.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Neurosurgery, Nippon Medical School, Japan

    Yudo Ishii MD, Masanori Suzuki MD, Michio Yamazaki MD, Naoko Sanno MD & Akira Teramoto MD

  2. Department of Pathology, Tokai University School of Medicine, 259-1193, Boseidai Isehara-city Kanagawa, Japan

    Susumu Takekoshi MD, Noboru Egashira, Shunsuke Miyai &  Robert Yoshiyuki Osamura MD

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  1. Yudo Ishii MD
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  2. Masanori Suzuki MD
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  3. Susumu Takekoshi MD
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  9. Robert Yoshiyuki Osamura MD
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Correspondence to Robert Yoshiyuki Osamura MD.

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Ishii, Y., Suzuki, M., Takekoshi, S. et al. Immunonegative null cell″adenomas and Gnadotropin (G) Subunit (Su) immunopositive adenomas share frequent expression of multiple transcription factors. Endocr Pathol 17, 35–44 (2006). https://doi.org/10.1385/EP:17:1:35

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