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Influence of polymorphisms of the dopamine D2 and somatostatin SST2 and SST5 genes in clinical manifestations and treatment of patients with pituitary adenomas

Grant number: 11/19932-5
Support Opportunities:Regular Research Grants
Duration: May 01, 2012 - April 30, 2014
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal Investigator:Andrea Glezer
Grantee:Andrea Glezer
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Pituitary adenomas represent 10% to 25% of all sellar lesions and can be classified according to tumor size (micro or macroadenoma) and to the profile of hormone secretion: clinically nonfunctioning adenomas (CNFA), prolactinomas, somatotrophinomas, corticotrophinomas, thyreotrophinomas and gonadotrophinomas. Clinical manifestations depend on hormonal hypersecretion and on mass effects. Surgical tumor removal is the primary treatment for corticotrophinomas, CNFA, non invasive somatotrophinomas or those with chiasmal compression, and prolactinomas resistant to medical treatment.Medical treatment can be performed with dopamine agonist (DA) and the response occurs in about 80% of prolactinomas, 10% of CNFA and 36% of corticotrophinomas. Clinical response to treatment depends on tumoral expression of dopamine D2 receptors and their subtypes (short and long). Additionally, a recent study pointed to the role of gene polymorphism of the D2 receptor in prolactinomas in response to this medical treatment. Another class of drugs available to treat somatotrophinomas and corticotrophinomas are somatostatin analogs (SA), which promote hormonal control in about 64% of somatotrofinomas and 76% of corticotrophinomas when used a multiligand analogue. Response to this treatment depends largely on tumoral expression of somatostatin receptors subtypes SSTR2 and SSTR5. There are some SSTR5 gene mutations and polymorphisms reported related to SA resistance mechanism.Our study´s main objective is to evaluate the correlation between gene polymorphism of D2, SSTR2 and SSTR5 receptor and the efficacy to treatment with dopamine agonists and somatostatin analogs in pituitary adenomas. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
BUENO, C. B. F.; TRARBACH, E. B.; BRONSTEIN, M. D.; GLEZER, A.. Cabergoline and prolactinomas: lack of association between DRD2 polymorphisms and response to treatment. Pituitary, v. 20, n. 3, p. 295-300, . (11/19932-5)

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