Expression of Peroxisome Proliferator-Activated Receptor alpha (PPARalpha) in somatotropinomas: Relationship with Aryl hydrocarbon receptor Interacting Protein (AIP) and in vitro effects of fenofibrate in GH cells.
[en] PURPOSE: To search for a possible role of Peroxisome Proliferator-Activated Receptor alpha (PPARalpha), a molecular partner of the Aryl hydrocarbon receptor Interacting Protein (AIP), in somatotropinomas. METHODS: Tumours from 51 acromegalic patients were characterized for PPARalpha and AIP expression by immunohistochemistry (IHC) and/or Real Time RT-PCR. Data were analysed according to tumour characteristics and pre-operative treatment with somatostatin analogues (SSA). The effects of fenofibrate were studied in GH3 cells in vitro. RESULTS: PPARalpha was expressed in most somatotropinomas. A modest relationship was found between PPARalpha and AIP expression, both being significantly higher in the presence of pre-operative SSA. However, only AIP expression was influenced by the response to treatment. Dual effects of fenofibrate were observed in GH3 cells, consisting of cell growth inhibition and an increase in GH secretion inhibited by octreotide. CONCLUSIONS: PPARalpha is a new player in somatotropinomas. Potential interactions between PPARalpha agonists and SSA may deserve further investigation.
Expression of Peroxisome Proliferator-Activated Receptor alpha (PPARalpha) in somatotropinomas: Relationship with Aryl hydrocarbon receptor Interacting Protein (AIP) and in vitro effects of fenofibrate in GH cells.
Publication date :
2016
Journal title :
Molecular and Cellular Endocrinology
ISSN :
0303-7207
eISSN :
1872-8057
Publisher :
Elsevier, Netherlands
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2016 Elsevier Ireland Ltd. All rights reserved.
Adkins J.C., Faulds D. Micronised fenofibrate: a review of its pharmacodynamic properties and clinical efficacy in the management of dyslipidaemia. Drugs 1997, 54:615-633.
Ambrosi B., Dall'Asta C., Cannavò S., Libé R., Vigo T., Epaminonda P., Chiodini I., Ferrero S., Trimarchi F., Arosio M., Beck-Peccoz P. Effects of chronic administration of PPAR-gamma ligand rosiglitazone in Cushing's disease. Eur. J. Endocrinol. 2004, 151:173-178.
Baschong W., Suetterlin R., Laeng R.H. Control of autofluorescence of archival formaldehyde-fixed, paraffin-embedded tissue in confocal laser scanning microscopy (CLSM). J. Histochem. Cytochem. 2001, 49:1565-1572.
Bastemir M., Akin F., Yaylali G.F. The PPAR-gamma activator rosiglitazone fails to lower plasma growth hormone and insulin-like growth factor-1 levels in patients with acromegaly. Neuroendocrinology 2007, 86:119-123.
Beckers A., Aaltonen L.A., Daly A.F., Karhu A. Familial isolated pituitary adenomas (FIPA) and the pituitary adenoma predisposition due to mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene. Endocr. Rev. 2013, 34:239-277. 10.1210/er.2012-1013.
Bell D.R., Poland A. Binding of aryl hydrocarbon receptor (AhR) to AhR-interacting protein. J. Biol. Chem. 2000, 275:36407-36414.
Ben-Shlomo A., Melmed S. Pituitary somatostatin receptor signaling. Trends Endocrinol. Metab. 2010, 21:123-133. 10.1016/j.tem.2009.12.003.
Binello E., Mormone E., Emdad L., Kothari H., Germano I.M. Characterization of fenofibrate-mediated anti-proliferative pro-apoptotic effects on high-grade gliomas and anti-invasive effects on glioma stem cells. J. Neurooncol 2014, 117:225-234. 10.1007/s11060-014-1385-6.
Blanquart C., Mansouri R., Fruchart J.C., Staels B., Glineur C. Different ways to regulate the PPARalpha stability. Biochem. Biophys. Res. Commun. 2004, 319:663-670.
Bogazzi F., Ultimieri F., Raggi F., Russo D., Vanacore R., Guida C., Viacava P., Cecchetti D., Acerbi G., Brogioni S., Cosci C., Gasperi M., Bartalena L., Martino E. PPARgamma inhibits GH synthesis and secretion and increases apoptosis of pituitary GH-secreting adenomas. Eur. J. Endocrinol. 2004, 150:863-875.
Chahal H.S., Trivellin G., Leontiou C.A., Alband N., Fowkes R.C., Tahir A., Igreja S.C., Chapple J.P., Jordan S., Lupp A., Schulz S., Ansorge O., Karavitaki N., Carlsen E., Wass J.A., Grossman A.B., Korbonits M. Somatostatin analogs modulate AIP in somatotroph adenomas: the role of the ZAC1 pathway. J. Clin. Endocrinol. Metab. 2012, 97:E1411-E1420. 10.1210/jc.2012-1111.
Daly A.F., Vanbellinghen J.F., Khoo S.K., Jaffrain-Rea M.L., Naves L.A., Guitelman M.A., Murat A., Emy P., Gimenez-Roqueplo A.P., Tamburrano G., Raverot G., Barlier A., De Herder W., Penfornis A., Ciccarelli E., Estour B., Lecomte P., Gatta B., Chabre O., Sabaté M.I., Bertagna X., Garcia Basavilbaso N., Stalldecker G., Colao A., Ferolla P., Wémeau J.L., Caron P., Sadoul J.L., Oneto A., Archambeaud F., Calender A., Sinilnikova O., Montañana C.F., Cavagnini F., Hana V., Solano A., Delettieres D., Luccio-Camelo D.C., Basso A., Rohmer V., Brue T., Bours V., Teh B.T., Beckers A. Aryl hydrocarbon receptor-interacting protein gene mutations in familial isolated pituitary adenomas: analysis in 73 families. J. Clin. Endocrinol. Metab. 2007, 92:1891-1896.
Dénes J., Kasuki L., Trivellin G., Colli L.M., Takiya C.M., Stiles C.E., Barry S., de Castro M., Gadelha M.R., Korbonits M. Regulation of aryl hydrocarbon receptor interacting protein (AIP) protein expression by MiR-34a in sporadic somatotropinomas. PLoS One 2015, 10:e0117107. 10.1371/journal.pone.0117107.
Formosa R., Xuereb-Anastasi A., Vassallo J. AIP regulates cAMP signalling and GH secretion in GH3 cells. Endocr. Relat. Cancer 2013, 20:495-505. 10.1530/ERC-13-0043.
Fratticci A., Grieco F.A., Spilioti C., Giangaspero F., Ventura L., Esposito V., Piccirilli M., Santoro A., Gulino A., Cantore G., Alesse E., Jaffrain-Rea M.L. Differential expression of neurogenins and NeuroD1 in human pituitary tumors. J. Endocrinol. 2007, 194:475-484.
Han X.F., Zhu Y.L., Hernandez M., Keating D.J., Chen C. Ghrelin reduces voltage-gated potassium currents in GH3 cells via cyclic GMP pathways. Endocrine 2005, 28:217-224.
Heaney A.P., Fernando M., Melmed S. PPAR-gamma receptor ligands: novel therapy for pituitary adenomas. J. Clin. Invest. 2003, 111:1381-1388.
Jaffrain-Rea M.L., Angelini M., Gargano D., Tichomirowa M.A., Daly A.F., Vanbellinghen J.F., D'Innocenzo E., Barlier A., Giangaspero F., Esposito V., Ventura L., Arcella A., Theodoropoulou M., Naves L.A., Fajardo C., Zacharieva S., Rohmer V., Brue T., Gulino A., Cantore G., Alesse E., Beckers A. Expression of aryl hydrocarbon receptor (AHR) and AHR-interacting protein in pituitary adenomas: pathological and clinical implications. Endocr. Relat. Cancer 2009, 16:1029-1043. 10.1677/ERC-09-0094.
Jaffrain-Rea M.L., Rotondi S., Turchi A., Occhi G., Barlier A., Peverelli E., Rostomyan L., Defilles C., Angelini M., Oliva M.A., Ceccato F., Maiorani O., Daly A.F., Esposito V., Buttarelli F., Figarella-Branger D., Giangaspero F., Spada A., Scaroni C., Alesse E., Beckers A. Somatostatin analogues increase AIP expression in somatotropinomas, irrespective of Gsp mutations. Endocr. Relat. Cancer 2013, 20:753-766. 10.1530/ERC-12-0322.
Kasuki Jomori de Pinho L., Vieira Neto L., Armondi Wildemberg L.E., Gasparetto E.L., Marcondes J., de Almeida Nunes B., Takiya C.M., Gadelha M.R. Low aryl hydrocarbon receptor-interacting protein expression is a better marker of invasiveness in somatotropinomas than Ki-67 and p53. Neuroendocrinology 2011, 94:39-48. 10.1159/000322787.
Katznelson L., Laws E.R., Melmed S., Molitch M.E., Murad M.H., Utz A., Wass J.A. Endocrine society. Acromegaly: an endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 2014, 99:3933-3951. 10.1210/jc.2014-2700.
Kida K., Nakajima M., Mohri T., Oda Y., Takagi S., Fukami T., Yokoi T. PPARα is regulated by miR-21 and miR-27b in human liver. Pharm. Res. 2011, 28:2467-2476. 10.1007/s11095-011-0473-y.
Koch M., Kreutz S., Böttger C., Benz A., Maronde E., Ghadban C., Korf H.W., Dehghani F. Palmitoylethanolamide protects dentate gyrus granule cells via peroxisome proliferator-activated receptor-α. Neurotox. Res. 2011, 19:330-340. 10.1007/s12640-010-9166-2.
König B., Rauer C., Rosenbaum S., Brandsch C., Eder K., Stangl G.I. Fasting upregulates PPARalpha target genes in brain and influences pituitary hormone expression in a PPARalpha dependent manner. PPAR Res. 2009, 801609. 10.1155/2009/801609.
Kota B.P., Huang T.H., Roufogalis B.D. An overview on biological mechanisms of PPARs. Pharmacol. Res. 2005, 51:85-94.
Kreutzer J., Jeske I., Hofmann B., Blumcke I., Fahlbusch R., Buchfelder M., Buslei R. No effect of the PPAR-gamma agonist rosiglitazone on ACTH or cortisol secretion in Nelson's syndrome and Cushing's disease in vitro and in vivo. Clin. Neuropathol. 2009, 28:430-443.
Leontiou C.A., Gueorguiev M., van der Spuy J., Quinton R., Lolli F., Hassan S., Chahal H.S., Igreja S.C., Jordan S., Rowe J., Stolbrink M., Christian H.C., Wray J., Bishop-Bailey D., Berney D.M., Wass J.A., Popovic V., Ribeiro-Oliveira A., Gadelha M.R., Monson J.P., Akker S.A., Davis J.R., Clayton R.N., Yoshimoto K., Iwata T., Matsuno A., Eguchi K., Musat M., Flanagan D., Peters G., Bolger G.B., Chapple J.P., Frohman L.A., Grossman A.B., Korbonits M. The role of the aryl hydrocarbon receptor-interacting protein gene in familial and sporadic pituitary adenomas. J. Clin. Endocrinol. Metab. 2008, 93:2390-2401. 10.1210/jc.2007-2611.
Li T., Zhang Q., Zhang J., Yang G., Shao Z., Luo J., Fan M., Ni C., Wu Z., Hu X. Fenofibrate induces apoptosis of triple-negative breast cancer cells via activation of NF-κB pathway. BMC Cancer 2014, 14:96. 10.1186/1471-2407-14-96.
Liu S.N., Liu Q., Li L.Y., Huan Y., Sun S.J., Shen Z.F. Long-term fenofibrate treatment impaired glucose-stimulated insulin secretion and up-regulated pancreatic NF-kappa B and iNOS expression in monosodium glutamate-induced obese rats: is that a latent disadvantage?. J. Transl. Med. 2011, 9:176. 10.1186/1479-5876-9-176.
Melmed S. Acromegaly. N. Engl. J. Med. 2006, 355:2558-2573.
Pozzi A., Capdevila J.H. PPARalpha ligands as antitumorigenic and antiangiogenic agents. PPAR Res. 2008, 2008:906542. 10.1155/2008/906542.
Pyper S.R., Viswakarma N., Yu S., Reddy J.K. PPARalpha: energy combustion, hypolipidemia, inflammation and cancer. Nucl. Recept. Signal 2010, 8:e002. 10.1621/nrs.08002.
Roberts R.A., Chevalier S., Hasmall S.C., James N.H., Cosulich S.C., Macdonald N. PPAR alpha and the regulation of cell division and apoptosis. Toxicology 2002, 181-182:167-170.
Shimomura K., Ikeda M., Ariyama Y., Proks P., Shimomura Y., Mori M., Matsumoto S. Effect of peroxisome proliferator-activated receptor alpha ligand fenofibrate on K(v) channels in the insulin-secreting cell line HIT-T15. Gen. Physiol. Biophys. 2006, 25:455-460.
Skrypnyk N., Chen X., Hu W., Su Y., Mont S., Yang S., Gangadhariah M., Wei S., Falck J.R., Jat J.L., Zent R., Capdevila J.H., Pozzi A. PPARα activation can help prevent and treat non-small cell lung cancer. Cancer Res. 2014, 74:621-631. 10.1158/0008-5472.CAN-13-1928.
Stojilkovic S. Molecular mechanisms of pituitary endocrine cell calcium handling. Cell Calcium 2012, 51:212-221. 10.1016/j.ceca.2011.11.003.
Sumanasekera W.K., Tien E.S., Turpey R., Vanden Heuvel J.P., Perdew G.H. Evidence that peroxisome proliferator-activated receptor alpha is complexed with the 90-kDa heat shock protein and the hepatitis virus B X-associated protein 2. J. Biol. Chem. 2003, 278:4467-4473.
Tong J.L., Zhang C.P., Nie F., Xu X.T., Zhu M.M., Xiao S.D., Ran Z.H. MicroRNA-506 regulates expression of PPAR alpha in hydroxycamptothecin-resistant human colon cancer cells. FEBS Lett. 2011, 58:3560-3568. 10.1016/j.febslet.2011.10.021.
Tolón R.M., Castillo A.I., Aranda A. Activation of the prolactin gene by peroxisome proliferator-activated receptor-alpha appears to be DNA binding-independent. J. Biol. Chem. 1998, 273:26652-26661.
Trivellin G., Butz H., Delhove J., Igreja S., Chahal H.S., Zivkovic V., McKay T., Patócs A., Grossman A.B., Korbonits M. MicroRNA miR-107 is overexpressed in pituitary adenomas and inhibits the expression of aryl hydrocarbon receptor-interacting protein in vitro. Am. J. Physiol. Endocrinol. Metab. 2012, 303:E708-E719. 10.1152/ajpendo.00546.2011.
Tuominen I., Heliövaara E., Raitila A., Rautiainen M.R., Mehine M., Katainen R., Donner I., Aittomäki V., Lehtonen H.J., Ahlsten M., Kivipelto L., Schalin-Jäntti C., Arola J., Hautaniemi S., Karhu A. AIP inactivation leads to pituitary tumorigenesis through defective Gα(i)-cAMP signaling. Oncogene 2015, 34:1174-1184. 10.1038/onc.2014.50.
Vierimaa O., Georgitsi M., Lehtonen R., Vahteristo P., Kokko A., Raitila A., Tuppurainen K., Ebeling T.M., Salmela P.I., Paschke R., Gündogdu S., De Menis E., Mäkinen M.J., Launonen V., Karhu A., Aaltonen L.A. Pituitary adenoma predisposition caused by germline mutations in the AIP gene. Science 2006, 312:1228-1230.
Wang W.L., Welsh J., Tenniswood M. 1,25-Dihydroxyvitamin D3 modulates lipid metabolism in prostate cancer cells through miRNA mediated regulation of PPARA. J. Steroid Biochem. Mol. Biol. 2013, 136:247-251. 10.1016/j.jsbmb.2012.09.033.
Winczyk K., Pawlikowski M. Immunohistochemical detection of PPARgamma receptors in the human pituitary adenomas: correlation with PCNA. Folia Histochem Cytobiol. 2005, 43:137-141.
Yang S.K., Parkington H.C., Blake A.D., Keating D.J., Chen C. Somatostatin increases voltage-gated K+ currents in GH3 cells through activation of multiple somatostatin receptors. Endocrinology 2005, 146:4975-4984.
Yang S.K., Steyn F., Chen C. Influence of membrane ion channel in pituitary somatotrophs by hypothalamic regulators. Cell Calcium 2012, 51:231-239. 10.1016/j.ceca.2011.12.005.