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CLINICAL STUDY |
1 Serviços de Endocrinologia, 2 Neurocirurgia, 3 Anatomia Patológica, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, Brazil, 4 Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil, 5 Serviço de Neurocirurgia do Hospital da Santa Casa de Misericórdia do Rio de Janeiro, Pontifícia Universidade Católica, Rio de Janeiro, Brazil, 6 Laboratório Diagnósticos da América, Rio de Janeiro, Brazil, 7 Instituto Estadual de Diabetes e Endocrinologia Luis Capriglione, Rio de Janeiro, Brazil and 8 Section of Endocrinology and Metabolism, Department of Medicine, University of Illinois at Chicago and Jesse Brown VA Medical Center, Chicago, Illinois, USA
(Correspondence should be addressed to M R Gadelha at Rua Nascimento Silva, 555/101 Ipanema, 22421-020 Rio de Janeiro, Brazil; Email: mgadelha{at}hucff.ufrj.br)
Objective: It is believed that the variable effectiveness of somatostatin analogs in post-surgical management of somatotropinomas and non-functioning pituitary adenomas (NFPA) may be due in part to variable expression of somatostatin receptor isoforms (SSTR1–5), within and between pituitary tumor types.
Design and methods: Quantitative real-time RT-PCR was used to compare absolute mRNA copy numbers for all five SSTR isoforms in 23 somatotropinomas and 19 NFPA.
Results: Somatostatin receptor subtype 5 mRNA was present at the highest level in somatotropinomas, followed by SSTR2>SSTR3>>SSTR1
SSTR4. In contrast, SSTR3 mRNA was present at the highest level in NFPA, followed by SSTR2, while SSTR1, SSTR4, and SSTR5 transcripts were only detectable in select tumors. Among somatotropinomas, a positive correlation was found between SSTR2 mRNA levels and the percent decrease of GH (%GH) after 3 and 6 months of therapy with octreotide long acting repeatable (LAR) (r=0.51 and r=0.66; P=0.05 and P=0.008). Also the percent decrease of IGF-I (%IGF-I) after 3 months of octreotide LAR was negatively correlated with SSTR5 and %IGF-I after 6 months of octreotide LAR was positively correlated with SSTR2.
Conclusions: The present report is a large series examining SSTR mRNA levels in somatotropinomas and NFPA. These initial findings suggest that detailed knowledge of the SSTR mRNA expression profile in somatotropinomas can help to predict the hormonal response to therapy with LAR. Also, it appears that SSTR3 in NFPA may be a potential target for SSTR3 preferential or universal ligands such as pasireotide.
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