Skip to main content

Advertisement

SpringerLink
Log in

Apoptosis: its role in pituitary development and neoplastic pituitary tissue

  • Published:
Pituitary Aims and scope Submit manuscript

Abstract

Apoptosis, also known as programmed cell death, is a phenomenon in which different stimuli trigger cellular mechanisms that culminate in death, in the absence of inflammatory cell response. Two different activation pathways are known, the intrinsic pathway (or mitochondrial) and extrinsic (or death-receptor pathway), both pathways trigger enzymatic reactions that lead cells to break up and be phagocytized by neighboring cells. This process is a common occurrence in physiological and pathological states, participating in the control of cell proliferation, differentiation and remodeling of organs. In the early steps of pituitary gland formation, numerous apoptotic cells are detected in the separation of Rathke’s pouch from the roof of oral ectoderm. In the distal part of the gland, which will form the adenohypophysis, the ratio of apoptosis was significantly lower. However, there is evidence that neoplastic pituitary cells undergo unbalance in genes that control apoptosis leading to uncontrolled cell growth. No direct evidence of apoptosis was found in the drugs used for tumors producing prolactin and growth hormone. In conclusion, an unbalancing in the apoptosis process is the boundary between development and tumor growth.

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

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Jin Z, El-deiry WS (2005) Overview of cell death signaling pathways. Cancer Biol Therapy 4(2):139–163

    Article  CAS  Google Scholar 

  2. Hotchkiss R, Strasser A, McDunn J, Swanson P (2009) Cell death. N Engl J Med 361(16):1570–1583

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Grivicich I, Regner A, Rocha AB (2007) Morte celular por apoptose. Revista Brasileira de Cancerologia 53(3):335–343

    Google Scholar 

  4. Sambaziotis D, Kapranos N, Kontogeorgos G (2003) Correlation of Bcl-2 and bax with apoptosis in human pituitary adenomas. Pituitary 5:127–133

    Article  Google Scholar 

  5. Saraga-babic M, Bazina M, Vukojevic K, Bocina I, Stefanovic V (2008) Involvement of pro-apoptotic and anti-apoptotic factors in the early development of the human pituitary gland. Histol Histopathol 23:1259–1268

    CAS  PubMed  Google Scholar 

  6. Davis SW, Castinetti F, Carvalho LR, Ellsworth BS, Potok MA, Lyons RH et al (2010) Molecular mechanisms of pituitary organogenesis: in search of novel regulatory genes. Mol Cell Endocrinol 323(1):4–19

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Ward RD, Raetzman LT, Suh H, Stone BM, Nasonkin IO, Camper SA (2005) Role of PROP1 in pituitary gland growth. Mol Endocrinol 19(3):698–710

    Article  CAS  PubMed  Google Scholar 

  8. Ward RD, Stone BM, Raetzman LT, Camper SA (2006) Cell proliferation and vascularization in mouse models of pituitary hormone deficiency. Mol Endocrinol 20(6):1378–1390

    Article  CAS  PubMed  Google Scholar 

  9. Melmed S (2003) Mechanisms for pituitary tumorigenesis: the plastic pituitary. J Clin Invest 112(11):1603–1618

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Chen L, Zhuang G, Li W, Liu Y, Zhang J, Tian X (2008) RGD-FasL induces apoptosis of pituitary adenoma cells. Cell Mol Immunol 5(1):61–68

    Article  CAS  PubMed  Google Scholar 

  11. Kontogeorgos G (2006) Predictive markers of pituitary adenoma behavior. Neuroendocrinology 83:179–188

    Article  CAS  PubMed  Google Scholar 

  12. Messini I, Kontogeorgos G, Kovacs K, Horvath E, Smyth HS (2002) Pituitary corticotroph adenoma containing many apoptotic cells: a histologic, immunohistochemical. Ultrastructural and molecular study. Ultrastruct Pathol 26:27–32

    Article  PubMed  Google Scholar 

  13. Kontogeorgos G, Horvath E, Kovacs K, Coire C, Lloyd RV, Scheithauer BW et al (2006) Morphologic changes of prolactin-producing pituitary adenomas after short treatment with dopamine agonists. Acta Neuropathol 111(1):46–52

    Article  PubMed  Google Scholar 

  14. Kulig E, Jin L, Qian X, Horvath E, Kovacs K, Stefaneanu L et al (1999) Apoptosis in nontumorous and neoplastic human pituitaries. Am J Pathol 154:3767–3774

    Article  Google Scholar 

  15. Ahlbom E, Grandison L, Zhivotovsky B, Ceccatelli S (1998) Termination of lactation induces apoptosis and alters the expression of the Bcl-2 family members in the rat anterior pituitary. Endocrinology 139(5):2465–2471

    CAS  PubMed  Google Scholar 

  16. Bronstein MD, Melmed S (2005) Tumorigênese Hipofisária. Arq Bras Endocrinol Metab 49(5):615–625

    Article  Google Scholar 

  17. Pinto EM, Bronstein MD (2008) Aspectos Moleculares da Tumorigênese Hipofisária. Arq Bras Endocrinol Metab 52(4):599–610

    Article  Google Scholar 

  18. Bronstein MD (2006) Acromegaly: molecular expression of somatostatin receptor subtypes and treatment outcome. Front Horm Res 35:129–135

    Article  CAS  PubMed  Google Scholar 

  19. Resmini E, Dadati P, Ravetti J-L, Zona G, Spaziante R, Saveanu A et al (2007) Rapid pituitary tumor shrinkage with dissociation between antiproliferative and antisecretory effects of a long-acting octreotide in an acromegalic patient. J Clin Endocrinol Metab 92(5):1592–1599

    Article  CAS  PubMed  Google Scholar 

  20. Sharma K, Patel YC, Srikant CB (1996) Subtype-selective induction of wild-type p53 and apoptosis, but not cell cycle arrest, by human somatostatin receptor 3. Mol Endocrinol 10(12):1688–1696

    CAS  PubMed  Google Scholar 

  21. Casarini APM, Pinto EM, Jallad RS, Giorgi RR, Giannella_Neto D, Bronstein MD (2006) Dissociation between tumor shrinkage and hormonal response during somatostatin analog treatment in an acromegalic patient: preferential expression of somatostatin receptor subtype 3. J Endocrinol Invest 29:826–830

    CAS  PubMed  Google Scholar 

  22. Losa M, Ciccarelli E, Mortini P, Barzaghi R, Gaia D, Faccani G et al (2001) Effects of octreotide treatment on the proliferation and apoptotic index of GH-secreting pituitary adenomas. J Clin Endocrinol Metab 86:5194–5200

    Article  CAS  PubMed  Google Scholar 

  23. Ferrante E, Pelegrini C, Bondioni S, Peverelli E, Locatelli M, Gelmini P et al (2006) Octreotide promotes apoptosis in human somatotroph tumor cells by activating somatostatin receptor type 2. Endocr Relat Cancer 13:955–962

    Article  CAS  PubMed  Google Scholar 

  24. Drewett N, Jacobi J, Willgoss D, Lloyd H (1993) Apoptosis in the anterior pituitary gland of the rat: studies with estrogen and bromocriptine. Neuroendocrinology 57(1):89–95

    Article  CAS  PubMed  Google Scholar 

  25. Yonezawa K, Tamaki N, Kokunai T (1997) Effects of bromocriptine and terguride on cell proliferation and apoptosis in the estrogen-stimulated anterior pituitary gland of the rat. Neurol Med Chir 37(12):901–906

    Article  CAS  Google Scholar 

  26. Stefaneanu L, Kovacs K, Scheithauer BW, Kontogeorgos G, Riehle DL, Sebo TJ et al (2000) Effect of dopamine agonists on lactotroph adenomas of the human pituitary. Endocr Pathol 11(04):341–352

    Article  CAS  PubMed  Google Scholar 

  27. Gruszka A, Kunert-radek J, Pawlikowski M (2004) The effect of octreotide and bromocriptine on expression of a pro-apoptotic Bax protein in rat prolactinoma. Folia Histochem Cytobiol 42(1):35–39

    CAS  PubMed  Google Scholar 

  28. Zatelli MC, Minoia M, Filieri C, Tagliati F, Buratto M, Ambrosio MR et al (2010) Effect of everolimus on cell viability in nonfunctioning pituitary adenomas. J Clin Endocrinol Metab 95(2):968–976

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

All authors stated no conflicts of interest.

Author information

Authors and Affiliations

  1. Neuroendocrine Unit, Division of Endocrinology and Metabolism, Hospital das Clínicas, University of Sao Paulo Medical School, São Paulo, Brazil

    M. F. Guzzo, L. R. S. Carvalho & M. D. Bronstein

  2. Av. Dr. Eneas de Carvalho, 255, 7ºandar, sala 7037, Instituto Central, Cerqueira Cesar, São Paulo, CEP 05403-000, Brazil

    M. D. Bronstein

Authors
  1. M. F. Guzzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L. R. S. Carvalho
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. D. Bronstein
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. D. Bronstein.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Guzzo, M.F., Carvalho, L.R.S. & Bronstein, M.D. Apoptosis: its role in pituitary development and neoplastic pituitary tissue. Pituitary 17, 157–162 (2014). https://doi.org/10.1007/s11102-013-0481-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11102-013-0481-5

Keywords

Search

Navigation