The enzyme succinate dehydrogenase (SDH) and its role in hereditary pituitary adenomas
https://doi.org/10.14341/omet2013410-15
Abstract
Despite active research involving familial pituitary adenomas and characterization of five hereditary syndromes, the genetic defects in more than 80 - 95% of patients remain not found. Besides, there is more than 25 cases of coexistence of pheochromocytomas and pituitary adenomas described in literature that up to date is not integrated in any syndrome; genetic defects of such coexistence also aren't defined. However it is supposed that in pituitary tumorigenesis, germline mutations of SDH can take part that is obviously important aspect of further investigation. Germline mutations of SDH were found in patients with different phenotypes of pituitary adenomas. Studying of mutations in genes SDHD, SDHB, SDHC, SDHA and their prevalence in patients with familial pituitary adenomas or with phenotypes of multiple endocrine neoplasia without mutations in MEN1, CDKN1B, PRKAR1A, AIP genes can provide clarity in a role of mutations in SDH in endocrine and in particular pituitary tumorigenesis.
Keywords
About the Authors
Iu Pankratovaaspirant otdeleniya neyroendokrinologiy i osteopatiy
E Przhiyalkovskaya
nauchnyy sotrudnik otdeleniya neyroendokrinologiy i osteopatiy
E Pigarova
starshiy nauchnyy sotrudnik otdeleniya neyroendokrinologiy i osteopatiy
L Dzeranova
glavnyy nauchnyy sotrudnik, d.m.n. otdeleniya neyroendokrinologiy i osteopatiy
References
1. Далантаева Н.С., Дедов И.И. Генетические и обменные особенности семейных изолированных аденом гипофиза. Ожирение и метаболизм. 2013; 2(35): 3–10.
2. Amar L, Baudin E, Burnichon N, Peyrard S, Silvera S, Bertherat J, Bertagna X, Schlumberger M, Jeunemaitre X, Gimenez-Roqueplo AP, Pierre-François Plouin. Succinate Dehydrogenase B Gene Mutations Predict Survival in Patients with Malignant Pheochromocytomas or Paragangliomas. JCEM. 2007; 92: 3822–3828.
3. Astuti D, Latif F, Dallol A, Dahia PL, Douglas F, George E, Skoldberg F, Husebye ES, Eng C, Maher ER. Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma. Am J Hum Genet. 2001; 69: 49–54.
4. Amar L, Bertherat J, Baudin E, Ajzenberg C, Bressac-de Paillerets B, Chabre O, Chamontin B, Delemer B, Giraud S, Murat A, Niccoli-Sire P, Richard S, Rohmer V, Sadoul JL, Strompf L, Schlumberger M, Bertagna X, Plouin PF, Jeunemaitre X, Gimenez-Roqueplo AP. Genetictesting in pheochromocytoma or functional paraganglioma. J Clin Oncol. 2005; 23: 8812–8818.
5. Burnichon N, Brière JJ, Libé R, Vescovo L, Rivière J, Tissier F, Jouanno E, Jeunemaitre X, Bénit P, Tzagoloff A, Rustin P, Bertherat J, Favier J, Gimenez-Roqueplo AP. SDHA is a tumor suppressor gene causing paraganglioma. Hum Mol Genet. 2010 August 1; 19(15): 3011–3020.
6. Brouwers FM, Eisenhofer G, Tao JJ, Kant JA, Adams KT, Linehan WM, Pacak K. High Frequency of SDHB Germline Mutations in Patients with Malignant Catecholamine-Producing Paragangliomas: Implications for Genetic Testing. JCEM. 2006; 91: 4505–4509.
7. Baysal BE, Ferrell RE, Willett-Brozick JE, Lawrence EC, Myssiorek D, Bosch A, van der May A, Taschner PEM, Rubinstein WS, Myers EN, Richard 3rd CW, Cornelisse CJ, Devilee P, Devlin B. Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. Science. 2000; 287: 848–851.
8. Breckenridge SM, Hamrahian AH, Faiman C, Suh J, Prayson R, Mayberg M. Coexistence of a pituitary macroadenoma and pheochromocytoma: a case report and review of the literature. Pituitary. 2003; 6: 221–225.
9. Benn DE, Gimenez-Roquepolo AP, Reilly JR, Bertherat J, Burgess J, Byth K, Croxson M, Dahia PL, Elston M, Gimm O et al. Clinical presentation and penetrance of pheochromocytomaparaganglioma syndromes. JCEM 2006; 91: 827–836.
10. Collins MT, Singer FR, Eugster E. McCune-Albright syndrome and the extraskeletal manifestations of fibrous dysplasia Orphanet. J Rare Dis. 2012; 7(Suppl 1): S4.
11. Chahal HS, Chapple JP, Frohman LA, Grossman AB, Korbonits M. Trends Clinical, genetic and molecular characterization of patients with familial isolated pituitary adenomas (FIPA). Endocrinol Metab. 2010 Jul; 21(7): 419–27.
12. Dwight T., Mann K., Benn DE., Robinson B G., McKelvie P, Gill AJ., Winship I, and CliftonBlighRJ.Familial SDHA Mutation Associated With Pituitary Adenoma andPheochromocytoma/Paraganglioma. JCEM. 2013; 98: E1103–E1108.
13. Douwes Dekker PB, Hogendoorn PC, Kuipers-Dijkshoorn N, Prins FA, van Duinen SG, Taschner PE, van der Mey AG, Cornelisse CJ. SDHD mutations in head and neck paragangliomas result in destabilization of complex II in the mitochondrial respiratory chain with loss of enzymatic activity and abnormal mitochondrial morphology. J Pathol. 2003; 201: 480–486.
14. Ezzat S, Asa SL, Couldwell WT, Barr CE, Dodge WE, Vance ML, McCutcheon IE. The prevalence of pituitary adenomas: a systematic review. Cancer. 2004; 101: 613–619.
15. Eng C, Kiuru M, Fernandez MJ, Aaltonen LA. A role for mitochondrial enzymes in inherited neoplasia and beyond. Nat Rev Cancer. 2003 Mar; 3(3): 193–202.
16. Fogg VC., Lanning NJ, MacKeiganJP Mitochondria in cancer: at the crossroads of life and deathChin. J Cancer. 2011 August; 30(8): 526–539.
17. Brouwers FM, Eisenhofer G, Tao JJ., Kant JA, Adams KT, Linehan WM, Pacak K. High Frequency of SDHB Germline Mutations in Patients with Malignant Catecholamine-Producing Paragangliomas: Implications for Genetic Testing. JCEM. 2006; 91: 4505–4509.
18. Gatenby RA, Gillies RJ. Why do cancers have high aerobic glycolysis? Nat Rev Cancer. 2004. Nov; 4(11): 891–9.
19. Gimenez-Roqueplo AP, Favier J, Rustin P, Mourad JJ, Plouin PF, Corvol P, Rotig A, Jeunemaitre X. The R22X mutation of the SDHD gene in hereditary paraganglioma abolishes the enzymatic activity of the complex II in the mitochondrial respiratory chain and activates the hypoxia pathway. Am J Hum Genet. 2001; 69:1186–1197.
20. Gimenez-Roquepolo AP, Favier J, Rustin P, Rieubland C, Crespin M, Nau V, Khau Van Kien P, Corvol P, Plouin PF, Jeunemaitre X. Mutations in the SDHB gene are associated with extra-adrenal andor malignant pheochromocytomas. Cancer Res. 2003; 63: 5615–5621.
21. Gimenez-Roquepolo AP, Favier J, Rustin P, Rieubland C, Kerlan V, Plouin PF, Rotig A, Jeunemaitre X. Functional consequences of a SDHB gene mutation in an apparently sporadic pheochromocytoma. J Clin Endocrinol Metab. 2002; 87: 4771–4774.
22. Granchi C, Minutolo F. Anti-cancer agents counteracting tumor glycolysis. ChemMedChem. 2012 August; 7(8): 1318–1350.
23. Hirawake H, Taniwaki M, Tamura A, Kojima S, Kita K. Cytochrome b in human complex II (succinate-ubiquinone oxidoreductase): cDNA cloning of the components in liver mitochondria and chromosome assignment of the genes for the large (SDHC) and small (SDHD) subunits to 1q21 and 11q23. Cytogenet. Cell Genet. 1997; 79 (1–2): 132–8.
24. Hirawake H, Wang H, Kuramochi T, Kojima S, Kita K. Human complex II (succinate-ubiquinone oxidoreductase: cDNA cloning of the flavoprotein (Fp) subunit of liver mitochondria. J. Biochem. July 1994; 116 (1): 221–7.
25. Igreja S, Chahal HS, King P, Bolger GB, Srirangalingam U, Guasti L, J Chapple P, Trivellin G, Gueorguiev M, Guegan K, Stals K, Khoo B, Kumar AV, Ellard S, Grossman AB, Korbonits M. Characterization of Aryl Hydrocarbon Receptor Interacting Protein (AIP) Mutations in Familial Isolated Pituitary Adenoma Families Human Mutation. 2010 August; 31(8): 950–960.
26. Kita K, Oya H, Gennis RB, Ackrell BA, Kasahara M. Human complex II (succinate-ubiquinone oxidoreductase): cDNA cloning of iron sulfur (Ip) subunit of liver mitochondria. Biochem. Biophys. Res. Commun. January 1990; 166 (1): 101–8.
27. King A, Selak M A and Gottlieb E. Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer. Oncogene. 2006; 25: 4675–4682.
28. Korpershoek E, Favier J, Gaal J, Burnichon N, Bram van Gessel, Oudijk L, Badoual C, Gadessaud N, Venisse A, Bayley Jean-Pierre, Marieke F. van Dooren, Wouter W. de Herder, Tissier F, Pierre-François Plouin, Francien H. van Nederveen, Winand NM Dinjens, Anne-Paule Gimenez-Roqueplo, Ronald R. de Krijger. SDHA Immunohistochemistry Detects Germline SDHA Gene Mutations in Apparently Sporadic. Paragangliomas and Pheochromocytomas. JCEM. 2011; 96: E1472–E1476.
29. Loriot C, Burnichon N, Gadessaud N, Vescovo L, Amar L, Libé R, Bertherat J, Plouin PF, Xavier J, Gimenez-Roqueplo AP, Favier J. Epithelial to Mesenchymal Transition Is Activated in Metastatic Pheochromocytomas and Paragangliomas Caused by SDHB Gene Mutations. JCEM. 2012; 97: E954–E962.
30. Kirschner LS. Mol Cell Endocrinol. PRKAR1A and the evolution of pituitary tumors. 2010 September 15; 326(1–2): 3–7.
31. Madhok BM, Yeluri S, Perry SL, Hughes TA, Jayne DG. Review Targeting glucose metabolism: an emerging concept for anticancer therapy. Am J Clin Oncol. 2011 Dec; 34(6): 628–35.
32. McWhinney SR, Pasini B, Stratakis CA, International Carney Triad and Carney-Stratakis Syndrome Consortium Familial gastrointestinal stromal tumors and germ-line mutations. N Engl J Med. 2007 Sep 6; 357(10): 1054–6.
33. Neumann HP, Pawlu C, Peczkowska M, Bausch B, McWhinney SR, Muresan M, Buchta M, Franke G, Klisch J, Bley TA, Hoegerle S, Boedeker CC, Opocher G, Schipper J, Januszewicz A, Eng C, European-American Paraganglioma Study Group. Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations. JAMA 2004; 292: 943–951.
34. Neumann HP, Bausch B, McWhinney SR, Bender BU, Gimm O, Franke G, Schipper J, Klisch J et al. Germline mutations in nonsyndromic pheochromocytoma NEngl J Med 2002; 346: 1459–1466.
35. Oyedotun KS, Lemire BD The quaternary structure of the Saccharomyces cerevisiae succinate dehydrogenase. Homology modeling, cofactor docking, and molecular dynamics simulation studies. J Biol Chem. 2004 Mar 5; 279(10): 9424–31.
36. Pellegata NS. MEN X and MEN 4 Clinics (Sao Paulo). 2012 April; 67(Suppl 1): 13–18.
37. Parfait B, Chretien D, Rotig A, Marsac C,Munnich A, Rustin P. Compound heterozygous mutations in the flavoprotein gene of therespiratory chain complex II in a patient with Leigh syndrome. HumGenet. 2000; 106: 236 –243.
38. Pasini B, Constantine A. Stratakis SDH mutations in tumourigenesis and inherited endocrine tumours. J Intern Med. 2009 July; 266(1): 19–42.
39. Robey RB, Hay N. Mitochondrial hexokinases: guardians of the mitochondria. Cell Cycle. 2005 May; 4(5): 654–8.
40. Rutter J, Winge DR, Schiffman JD. Succinate Dehydrogenase—Assembly, Regulation and Role in Human Disease. Mitochondrion. 2010 June; 10(4): 393–401.
41. Ricketts C, Woodward ER, Killick P, Morris MR, Astuti D, Latif F, Maher ER Germline SDHB mutations and familial renal cell carcinoma. J Natl Cancer Inst. 2008 Sep 3; 100(17): 1260–2.
42. Thakker R.V. Multiple endocrine neoplasia type 1 (MEN1) Best Pract Res Clin Endocrinol Metab. 2010; 24(3): 355–70.
43. Vandeva S, Jaffrain-Rea ML, Daly AF, Tichomirowa M, Zacharieva S, Beckers A. The genetics of pituitary adenomas. Best Pract Res Clin Endocrinol Metab. 2010 Jun; 24(3): 461–76.
44. Vanharanta S, Buchta M, McWhinney SR, Virta SK, Peçzkowska M, Morrison CD, Lehtonen R, Januszewicz A, Järvinen H, Juhola M, Mecklin JP, Pukkala E, Herva R, Kiuru M, Nupponen NN, Aaltonen LA, Neumann HP, Eng C. Early-onset renal cell carcinoma as a novel extraparaganglial component of SDHB-associated heritable paraganglioma. Am J Hum Genet. 2004 Jan; 74(1): 153–9.
45. Yankovskaya V, Horsefield R, et al. Architecture of succinate dehydrogenase and reactive oxygen species generation. Science. 2003; 299(5607): 700–704.
46. Zhang J, Frerman FE, et al. Structure of electron transfer flavoprotein-ubiquinone oxidoreductase and electron transfer to the mitochondrial ubiquinone pool. Proc Natl Acad Sci U S A. 2006; 103(44): 16212–16217.
47. Xekouki P, Pacak K, Almeida M, Christopher A. Wassif, Rustin P, Nesterova M, de la Luz Sierra M, Matro J, Ball E, Azevedo M, Horvath A, Lyssikatos Ch, Quezado M, Patronas N, Ferrando B, Pasini B, Lytras A, Tolis G, and Stratakis CA Succinate Dehydrogenase (SDH) D Subunit (SDHD) Inactivation in a Growth-Hormone-Producing Pituitary Tumor: A New Association for SDH? JCEM. 2012; 97: E357–E366.
Review
For citations:
, , , The enzyme succinate dehydrogenase (SDH) and its role in hereditary pituitary adenomas. Obesity and metabolism. 2013;10(4):10-15. (In Russ.) https://doi.org/10.14341/omet2013410-15
Views:
783
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0).
Email this article 
