Expression Analysis of Dopamine Receptor Subtypes in Normal Human Pituitaries, Nonfunctioning Pituitary Adenomas and Somatotropinomas, and the Association between Dopamine and Somatostatin Receptors with Clinical Response to Octreotide-LAR in Acromegaly
| Autor: | Rhonda D. Kineman, Raúl M. Luque, Leonardo Pereira Quintella, Leila Chimelli, Giselle F. Taboada, Leonardo Vieira Neto, Denise P. Carvalho, Paulo Niemeyer, Jorge Marcondes, Mônica R. Gadelha, Evelyn de Oliveira Machado |
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| Rok vydání: | 2009 |
| Předmět: |
Adenoma
endocrine system Pituitary gland medicine.medical_specialty Endocrinology Diabetes and Metabolism Clinical Biochemistry chemical and pharmacologic phenomena Biology Pituitary neoplasm Octreotide Biochemistry Receptors Dopamine Endocrinology Pituitary adenoma Internal medicine Acromegaly medicine Humans Protein Isoforms Pituitary Neoplasms RNA Messenger Receptors Somatostatin Somatostatin receptor Gene Expression Profiling Biochemistry (medical) medicine.disease Gene Expression Regulation Neoplastic medicine.anatomical_structure Somatostatin Dopamine receptor Delayed-Action Preparations Pituitary Gland Original Article Growth Hormone-Secreting Pituitary Adenoma hormones hormone substitutes and hormone antagonists |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 94:1931-1937 |
| ISSN: | 1945-7197 0021-972X |
| Popis: | Dopamine receptor (DR) and somatostatin receptor subtype expression in pituitary adenomas may predict the response to postsurgical therapies.Our objectives were to assess and compare the mRNA levels of DR1-5 and somatostatin receptors 1-5 in normal pituitaries (NPs), nonfunctioning pituitary adenomas (NFPAs), and somatotropinomas. In addition, we determined whether the level of DR expression correlates with the in vivo response to octreotide-LAR in acromegalic patients.Eight NPs, 30 NFPAs, and 39 somatotropinomas were analyzed for receptor mRNA levels by real-time RT-PCR. The DR2 short variant was estimated as the DR2 long/DR2 total (DR2T). The relationship between DR expression and the postsurgical response to octreotide-LAR was assessed in 19 of the acromegalic patients.DR3 was not detected. The relationship between expression levels of DR subtypes in NPs and somatotropinomas was DR2TDR4DR5DR1, whereas in NFPAs, DR2TDR4DR1DR5. The DR2 short variant was the predominant DR2 variant in the majority of samples. In acromegalics treated with octreotide-LAR, DR1 was negatively correlated with percent GH reduction (3 months: r = -0.67, P = 0.002; and 6 months: r = -0.58, P = 0.009), and DR5 was positively correlated with percent IGF-I reduction (3 months: r = 0.55, P = 0.01; and 6 months: r = 0.47, P = 0.04).DR2 is the predominant DR subtype in NPs, NFPAs, and somatotropinomas. The fact that DR1, DR4, and DR5 are also expressed in many adenomas tested suggests that these receptors might also play a role in the therapeutic impact of postsurgical medical therapies in patients with NFPA and acromegaly. This was supported by the finding that the in vivo response to octreotide-LAR was negatively associated with DR1 and positively associated with DR5. |
| Databáze: | OpenAIRE |
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