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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

Endocrinology (L.V.N., E.d.O.M., G.F.T., M.R.G.), Neurosurgery (J.B.M.), and Pathology (L.M.C.C.) Sections, Hospital Universitário Clementino Fraga Filho, Instituto de Biofísica Carlos Chagas Filho (D.P.d.C.), Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-913, Brazil; Pathology Section (L.P.Q.), Instituto de Pesquisa Clínica Evandro Chagas, Fiocruz, Rio de Janeiro 21040-360, Brazil; Neurosurgery Section (P.N.), Hospital Santa Casa de Misericórdia do Rio de Janeiro, Rio de Janeiro 20021-230, Brazil; Instituto Estadual de Diabetes e Endocrinologia Luis Capriglione (M.R.G.), Rio de Janeiro 20211-340, Brazil; Department of Cell Biology Physiology and Immunology (R.M.L.), University of Cordoba, 14004 Córdoba, Spain; and Section of Endocrinology, Diabetes and Metabolism (R.M.L., R.D.K.), Department of Medicine, University of Illinois at Chicago and Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois 60612

Address all correspondence and requests for reprints to: Mônica R. Gadelha, M.D., Ph.D., Rua Nascimento Silva, 555/101, Ipanema, Rio de Janeiro 22421-020, Brazil. E-mail: mgadelha{at}hucff.ufrj.br.

Context: Dopamine receptor (DR) and somatostatin receptor subtype expression in pituitary adenomas may predict the response to postsurgical therapies.

Objectives: 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.

Design and 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.

Results: DR3 was not detected. The relationship between expression levels of DR subtypes in NPs and somatotropinomas was DR2TDR4>>DR5>DR1, whereas in NFPAs, DR2TDR4>>DR1>DR5. 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).

Conclusions: 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.