Quantitative analysis of somatostatin receptor subtype (SSTR1-5) gene expression levels in somatotropinomas and non-functioning pituitary adenomas.
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.


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.
Taboada
Giselle F
GF
Serviços de Endocrinologia, Neurocirurgia, Anatomia Patológica, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, Brazil.
Luque
Raul M
RM
Bastos
Wildebranham
W
Guimarães
Renata F C
RF
Marcondes
Jorge B
JB
Chimelli
Leila M C
LM
Fontes
Rosita
R
Mata
Paulo J P
PJ
Filho
Paulo Niemeyer
PN
Carvalho
Denise P
DP
Kineman
Rhonda D
RD
Gadelha
Mônica R
MR
D000172:Acromegaly / Q000209:etiology; D000236:Adenoma / Q000378:metabolism* / Q000601:surgery; D000328:Adult; D016375:Antisense Elements (Genetics); D017931:DNA Primers; D005260:Female; D005500:Follow-Up Studies; D018628:Gene Dosage; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015282:Octreotide / Q000627:therapeutic use; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000601:surgery; D012333:RNA, Messenger / Q000096:biosynthesis; D017481:Receptors, Somatostatin / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016375:Antisense Elements (Genetics); D017931:DNA Primers; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; D019382:Human Growth Hormone; D015282:Octreotide