Skip to main content
SpringerLink
Log in

Adult Pituitary Stem Cells

  • Chapter
  • First Online:
Book cover Adult Stem Cells

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

Abstract

Underlying mechanisms leading to pituitary plasticity by which the gland adapts the number of hormone-producing cell to the continuously changing physiological requirements are still poorly understood. Adult stem cells were shown to direct homeostatic cell maintenance, regeneration, and functional plasticity in several organs and tissues. Only recently potential stem cells were identified and phenotypically characterized in adult pituitary. Multiple possible stem/progenitor cell candidates were proposed, but different studies have been only partially reconciled. Here, we critically analyzed the reports addressing the identification of adult pituitary stem cells, trying, when possible, to reunite the results of the different studies. Nonetheless, in light of the still non-complete characterization of these cells, some discrepancies among the published studies are still apparent. Importantly, long-term in vitro self-renewal, a defining feature of stem cells, remains to be unequivocally demonstrated. Finally, the potential role of adult pituitary stem (or progenitor) cells in pituitary adenoma development will be discussed.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

CSC:

Cancer stem cells

FCS:

Fetal calf serum

FS cells:

Folliculo-stellate cells

GPS cells:

GFRα2-PROP1-STEM cells

HMG:

High mobility group

MP:

Main population

PASCs:

Pituitary adenoma stem-like cells

Sca1:

Stem cell antigen 1

SMA:

Smooth muscle actin

SP:

Side population

TIC:

Tumor-initiating cells

References

  1. Yoshimura F, Harumiya K, Ishikawa H, Otsuka Y (1969) Differentiation of isolated chromophobes into acidophils or basophils when transplanted into the hypophysiotrophic area of hypothalamus. Endocrinol Jpn 16:531–540

    Article  PubMed  CAS  Google Scholar 

  2. Kawamura K, Kouki T, Kawahara G, Kikuyama S (2002) Hypophyseal development in vertebrates from amphibians to mammals. Gen Comp Endocrinol 126:130–135

    Article  PubMed  CAS  Google Scholar 

  3. Castinetti F, Davis SW, Brue T, Camper SA (2011) Pituitary stem cell update and potential implications for treating hypopituitarism. Endocr Rev 32:453–471

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  4. Bilodeau S, Roussel-Gervais A, Drouin J (2009) Distinct developmental roles of cell cycle inhibitors p57Kip2 and p27Kip1 distinguish pituitary progenitor cell cycle exit from cell cycle reentry of differentiated cells. Mol Cell Biol 29:1895–1908

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  5. Vankelecom H (2010) Pituitary stem/progenitor cells: embryonic players in the adult gland? Eur J Neurosci 32:2063–2081

    Article  PubMed  Google Scholar 

  6. Carbajo-Perez E, Watanabe YG (1990) Cellular proliferation in the anterior pituitary of the rat during the postnatal period. Cell Tissue Res 261:333–338

    Article  PubMed  CAS  Google Scholar 

  7. Levy A (2008) Molecular and trophic mechanisms of tumorigenesis. Endocrinol Metab Clin North Am 37:23–50, vii

    Article  PubMed  CAS  Google Scholar 

  8. Levy A (2002) Physiological implications of pituitary trophic activity. J Endocrinol 174:147–155

    Article  PubMed  CAS  Google Scholar 

  9. Levy A (2008) Stem cells, hormones and pituitary adenomas. J Neuroendocrinol 20:139–140

    Article  PubMed  CAS  Google Scholar 

  10. Nolan LA, Kavanagh E, Lightman SL, Levy A (1998) Anterior pituitary cell population control: basal cell turnover and the effects of adrenalectomy and dexamethasone treatment. J Neuroendocrinol 10:207–215

    Article  PubMed  CAS  Google Scholar 

  11. Nolan LA, Levy A (2006) The effects of testosterone and oestrogen on gonadectomised and intact male rat anterior pituitary mitotic and apoptotic activity. J Endocrinol 188:387–396

    Article  PubMed  CAS  Google Scholar 

  12. Nolan LA, Levy A (2009) The trophic effects of oestrogen on male rat anterior pituitary lactotrophs. J Neuroendocrinol 21:457–464

    Article  PubMed  CAS  Google Scholar 

  13. Kominami R, Yasutaka S, Taniguchi Y, Shinohara H (2003) Proliferating cells in the rat anterior pituitary during the postnatal period: immunoelectron microscopic observations using monoclonal anti-bromodeoxyuridine antibody. Histochem Cell Biol 120:223–233

    Article  PubMed  CAS  Google Scholar 

  14. Frawley LS, Boockfor FR (1991) Mammosomatotropes: presence and functions in normal and neoplastic pituitary tissue. Endocr Rev 12:337–355

    Article  PubMed  CAS  Google Scholar 

  15. Vankelecom H (2007) Stem cells in the postnatal pituitary? Neuroendocrinology 85:110–130

    Article  PubMed  CAS  Google Scholar 

  16. McNicol AM, Carbajo-Perez E (1999) Aspects of anterior pituitary growth, with special reference to corticotrophs. Pituitary 1:257–268

    Article  PubMed  CAS  Google Scholar 

  17. Rizzoti K (2010) Adult pituitary progenitors/stem cells: from in vitro characterization to in vivo function. Eur J Neurosci 32:2053–2062

    Article  PubMed  Google Scholar 

  18. Castrique E, Fernandez-Fuente M, Le Tissier P, Herman A, Levy A (2010) Use of a prolactin-Cre/ROSA-YFP transgenic mouse provides no evidence for lactotroph transdifferentiation after weaning, or increase in lactotroph/somatotroph proportion in lactation. J Endocrinol 205:49–60

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  19. Kelberman D, Rizzoti K, Lovell-Badge R, Robinson IC, Dattani MT (2009) Genetic regulation of pituitary gland development in human and mouse. Endocr Rev 30:790–829

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  20. Florio T (2011) Adult pituitary stem cells: from pituitary plasticity to adenoma development. Neuroendocrinology 94:265–277

    Article  PubMed  CAS  Google Scholar 

  21. Furusawa C, Kaneko K (2012) A dynamical-systems view of stem cell biology. Science 338:215–217

    Article  PubMed  CAS  Google Scholar 

  22. Kim M, Morshead CM (2003) Distinct populations of forebrain neural stem and progenitor cells can be isolated using side-population analysis. J Neurosci 23:10703–10709

    PubMed  CAS  Google Scholar 

  23. Challen GA, Little MH (2006) A side order of stem cells: the SP phenotype. Stem Cells 24:3–12

    Article  PubMed  Google Scholar 

  24. Chen J, Hersmus N, Van Duppen V, Caesens P, Denef C, Vankelecom H (2005) The adult pituitary contains a cell population displaying stem/progenitor cell and early embryonic characteristics. Endocrinology 146:3985–3998

    Article  PubMed  CAS  Google Scholar 

  25. van Rijn SJ, Gremeaux L, Riemers FM, Brinkhof B, Vankelecom H, Penning LC, Meij BP (2012) Identification and characterisation of side population cells in the canine pituitary gland. Vet J 192:476–482

    Article  PubMed  CAS  Google Scholar 

  26. Chen J, Crabbe A, Van Duppen V, Vankelecom H (2006) The notch signaling system is present in the postnatal pituitary: marked expression and regulatory activity in the newly discovered side population. Mol Endocrinol 20:3293–3307

    Article  PubMed  CAS  Google Scholar 

  27. Dontu G, Abdallah WM, Foley JM, Jackson KW, Clarke MF, Kawamura MJ, Wicha MS (2003) In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev 17:1253–1270

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  28. Seaberg RM, Smukler SR, Kieffer TJ, Enikolopov G, Asghar Z, Wheeler MB, Korbutt G, van der Kooy D (2004) Clonal identification of multipotent precursors from adult mouse pancreas that generate neural and pancreatic lineages. Nat Biotechnol 22:1115–1124

    Article  PubMed  CAS  Google Scholar 

  29. Chen J, Gremeaux L, Fu Q, Liekens D, Van Laere S, Vankelecom H (2009) Pituitary progenitor cells tracked down by side population dissection. Stem Cells 27:1182–1195

    Article  PubMed  CAS  Google Scholar 

  30. Fauquier T, Rizzoti K, Dattani M, Lovell-Badge R, Robinson IC (2008) SOX2-expressing progenitor cells generate all of the major cell types in the adult mouse pituitary gland. Proc Natl Acad Sci USA 105:2907–2912

    Article  PubMed Central  PubMed  Google Scholar 

  31. Garcia-Lavandeira M, Quereda V, Flores I, Saez C, Diaz-Rodriguez E, Japon MA, Ryan AK, Blasco MA, Dieguez C, Malumbres M, Alvarez CV (2009) A GRFa2/Prop1/stem (GPS) cell niche in the pituitary. PLoS One 4:e4815

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  32. Gremeaux, L, Fu QV, Van Duppen V, Van den broeck A, Wouters J, van Loon J, Bex M, and Vankelecom H (2009) Cancer stem cells in human pituitary adenoma: identification and characterization of a tumor ‘side population’. In: Abstract, Oncoforum 2009. Leuven, Belgium

    Google Scholar 

  33. Cherqui S, Kurian SM, Schussler O, Hewel JA, Yates JR 3rd, Salomon DR (2006) Isolation and angiogenesis by endothelial progenitors in the fetal liver. Stem Cells 24:44–54

    Article  PubMed  CAS  Google Scholar 

  34. Pevny LH, Nicolis SK (2010) Sox2 roles in neural stem cells. Int J Biochem Cell Biol 42:421–424

    Article  PubMed  CAS  Google Scholar 

  35. Alatzoglou KS, Kelberman D, Dattani MT (2009) The role of SOX proteins in normal pituitary development. J Endocrinol 200:245–258

    Article  PubMed  CAS  Google Scholar 

  36. Yoshida S, Kato T, Yako H, Susa T, Cai LY, Osuna M, Inoue K, Kato Y (2011) Significant quantitative and qualitative transition in pituitary stem / progenitor cells occurs during the postnatal development of the rat anterior pituitary. J Neuroendocrinol 23:933–943

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  37. Kawakami Y, Rodriguez-Leon J, Izpisua Belmonte JC (2006) The role of TGFbetas and Sox9 during limb chondrogenesis. Curr Opin Cell Biol 18:723–729

    Article  PubMed  CAS  Google Scholar 

  38. Sekido R (2010) SRY: a transcriptional activator of mammalian testis determination. Int J Biochem Cell Biol 42:417–420

    Article  PubMed  CAS  Google Scholar 

  39. Taranova OV, Magness ST, Fagan BM, Wu Y, Surzenko N, Hutton SR, Pevny LH (2006) SOX2 is a dose-dependent regulator of retinal neural progenitor competence. Genes Dev 20:1187–1202

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  40. Fu Q, Gremeaux L, Luque RM, Liekens D, Chen J, Buch T, Waisman A, Kineman R, Vankelecom H (2012) The adult pituitary shows stem/progenitor cell activation in response to injury and is capable of regeneration. Endocrinology 153:3224–3235

    Article  PubMed  CAS  Google Scholar 

  41. Fu Q, Vankelecom H (2012) Regenerative capacity of the adult pituitary: multiple mechanisms of lactotrope restoration after transgenic ablation. Stem Cells Dev 21(18):3245–3257

    Article  PubMed  CAS  Google Scholar 

  42. Krylyshkina O, Chen J, Mebis L, Denef C, Vankelecom H (2005) Nestin-immunoreactive cells in rat pituitary are neither hormonal nor typical folliculo-stellate cells. Endocrinology 146:2376–2387

    Article  PubMed  CAS  Google Scholar 

  43. Gleiberman AS, Michurina T, Encinas JM, Roig JL, Krasnov P, Balordi F, Fishell G, Rosenfeld MG, Enikolopov G (2008) Genetic approaches identify adult pituitary stem cells. Proc Natl Acad Sci USA 105:6332–6337

    Article  PubMed Central  PubMed  Google Scholar 

  44. Weiss S, Siebzehnrubl FA, Kreutzer J, Blumcke I, Buslei R (2009) Evidence for a progenitor cell population in the human pituitary. Clin Neuropathol 28:309–318

    Article  PubMed  CAS  Google Scholar 

  45. Galichet C, Lovell-Badge R, Rizzoti K (2010) Nestin-Cre mice are affected by hypopituitarism, which is not due to significant activity of the transgene in the pituitary gland. PLoS One 5:e11443

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  46. Ward RD, Raetzman LT, Suh H, Stone BM, Nasonkin IO, Camper SA (2005) Role of PROP1 in pituitary gland growth. Mol Endocrinol 19:698–710

    Article  PubMed  CAS  Google Scholar 

  47. Yoshida S, Kato T, Susa T, Cai LY, Nakayama M, Kato Y (2009) PROP1 coexists with SOX2 and induces PIT1-commitment cells. Biochem Biophys Res Commun 385:11–15

    Article  PubMed  CAS  Google Scholar 

  48. Garcia-Lavandeira M, Saez C, Diaz-Rodriguez E, Perez-Romero S, Senra A, Dieguez C, Japon MA, Alvarez CV (2012) Craniopharyngiomas express embryonic stem cell markers (SOX2, OCT4, KLF4, and SOX9) as pituitary stem cells but do not coexpress RET/GFRA3 receptors. J Clin Endocrinol Metab 97:E80–E87

    Article  PubMed  CAS  Google Scholar 

  49. Lepore DA, Roeszler K, Wagner J, Ross SA, Bauer K, Thomas PQ (2005) Identification and enrichment of colony-forming cells from the adult murine pituitary. Exp Cell Res 308:166–176

    Article  PubMed  CAS  Google Scholar 

  50. Bowie EP, Ishikawa H, Shiino M, Rennels EG (1978) An immunocytochemical study of a rat pituitary multipotential clone. J Histochem Cytochem 26:94–97

    Article  PubMed  CAS  Google Scholar 

  51. Shiino M, Ishikawa H, Rennels EG (1977) In vitro and in vivo studies on cytodifferentiation of pituitary clonal cells derived from the epithelium of Rathke’s pouch. Cell Tissue Res 181:473–485

    Article  PubMed  CAS  Google Scholar 

  52. Otto C, tom Dieck S, Bauer K (1996) Dipeptide uptake by adenohypophysial folliculostellate cells. Am J Physiol 271:C210–C217

    PubMed  CAS  Google Scholar 

  53. Lepore DA, Thomas GP, Knight KR, Hussey AJ, Callahan T, Wagner J, Morrison WA, Thomas PQ (2007) Survival and differentiation of pituitary colony-forming cells in vivo. Stem Cells 25:1730–1736

    Article  PubMed  CAS  Google Scholar 

  54. Osuna M, Yako H, Yoshida S, Sonobe Y, Inoue K, Kato T, Kato Y (2011) S100b-expressing folliculo-stellate cells are found in SOX2-positive population in the anterior pituitary lobe and show multiple differentiation capacities in the defined culture conditions. Endocr Rev 32:P1–P386

    Article  Google Scholar 

  55. Lepore DA, Jokubaitis VJ, Simmons PJ, Roeszler KN, Rossi R, Bauer K, Thomas PQ (2006) A role for angiotensin-converting enzyme in the characterization, enrichment, and proliferation potential of adult murine pituitary colony-forming cells. Stem Cells 24:2382–2390

    Article  PubMed  CAS  Google Scholar 

  56. Reya T, Morrison SJ, Clarke MF, Weissman IL (2001) Stem cells, cancer, and cancer stem cells. Nature 414:105–111

    Article  PubMed  CAS  Google Scholar 

  57. Soltysova A, Altanerova V, Altaner C (2005) Cancer stem cells. Neoplasma 52:435–440

    PubMed  CAS  Google Scholar 

  58. Cerdan C, Bhatia M (2010) Novel roles for Notch, Wnt and Hedgehog in hematopoesis derived from human pluripotent stem cells. Int J Dev Biol 54:955–963

    Article  PubMed  CAS  Google Scholar 

  59. Krupkova O Jr, Loja T, Zambo I, Veselska R (2010) Nestin expression in human tumors and tumor cell lines. Neoplasma 57:291–298

    Article  PubMed  Google Scholar 

  60. Zhou BB, Zhang H, Damelin M, Geles KG, Grindley JC, Dirks PB (2009) Tumour-initiating cells: challenges and opportunities for anticancer drug discovery. Nat Rev Drug Discov 8:806–823

    Article  PubMed  CAS  Google Scholar 

  61. Gaston-Massuet C, Andoniadou CL, Signore M, Jayakody SA, Charolidi N, Kyeyune R, Vernay B, Jacques TS, Taketo MM, Le Tissier P, Dattani MT, Martinez-Barbera JP (2011) Increased Wingless (Wnt) signaling in pituitary progenitor/stem cells gives rise to pituitary tumors in mice and humans. Proc Natl Acad Sci USA 108:11482–11487

    Article  PubMed Central  PubMed  Google Scholar 

  62. Alatzoglou KS, Andoniadou CL, Kelberman D, Kim HG, Botse-Baidoo E, Pedersen-White JR, Layman LC, Martinez-Barbera JP, Dattani MT (2011) Clinical manifestations of a novel SOX2 mutation may result from failure to repress β-catenin-mediated target activation: suggestion for a new mechanism for the interaction between SOX2 and β-catenin. Endocr Rev 32:P3–P758

    Article  CAS  Google Scholar 

  63. Camper SA (2011) Beta-catenin stimulates pituitary stem cells to form aggressive tumors. Proc Natl Acad Sci USA 108:11303–11304

    Article  PubMed Central  PubMed  Google Scholar 

  64. Hosoyama T, Nishijo K, Garcia MM, Schaffer BS, Ohshima-Hosoyama S, Prajapati SI, Davis MD, Grant WF, Scheithauer BW, Marks DL, Rubin BP, Keller C (2010) A postnatal Pax7 progenitor gives rise to pituitary adenomas. Genes Cancer 1:388–402

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  65. Melmed S (2011) Pathogenesis of pituitary tumors. Nat Rev Endocrinol 7:257–266

    Article  PubMed  CAS  Google Scholar 

  66. Miller RJ, Banisadr G, Bhattacharyya BJ (2008) CXCR4 signaling in the regulation of stem cell migration and development. J Neuroimmunol 198:31–38

    Article  PubMed  CAS  Google Scholar 

  67. Barbieri F, Bajetto A, Stumm R, Pattarozzi A, Porcile C, Zona G, Dorcaratto A, Ravetti JL, Minuto F, Spaziante R, Schettini G, Ferone D, Florio T (2008) Overexpression of stromal cell-derived factor 1 and its receptor CXCR4 induces autocrine/paracrine cell proliferation in human pituitary adenomas. Clin Cancer Res 14:5022–5032

    Article  PubMed  CAS  Google Scholar 

  68. Barbieri F, Bajetto A, Pattarozzi A, Gatti M, Würth R, Porcile C, Thellung S, Corsaro A, Villa V, Nizzari M, Florio T (2011) The chemokine SDF1/CXCL12: a novel autocrine/paracrine factor involved in pituitary adenoma development. Open Neuroendocrinol J 4:64–76

    Article  CAS  Google Scholar 

  69. Xu Q, Yuan X, Tunici P, Liu G, Fan X, Xu M, Hu J, Hwang JY, Farkas DL, Black KL, Yu JS (2009) Isolation of tumour stem-like cells from benign tumours. Br J Cancer 101:303–311

    Article  PubMed Central  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by a grant from the Italian association for Cancer Research (AIRC).

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Section of Pharmacology, and Center of Excellence for Biomedical Research, University of Genova, Genova, Italy

    Tullio Florio

Authors
  1. Tullio Florio
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tullio Florio .

Editor information

Editors and Affiliations

  1. Regenerative Medicine Program, Ottawa Hospital Research Institute Sprott Centre for Stem Cell Research, Ottawa, Ontario, Canada

    Kursad Turksen

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this chapter

Cite this chapter

Florio, T. (2014). Adult Pituitary Stem Cells. In: Turksen, K. (eds) Adult Stem Cells. Stem Cell Biology and Regenerative Medicine. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4614-9569-7_5

Download citation

Publish with us

Policies and ethics

Search

Navigation