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


OBJECTIVE
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.


METHODS
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 DR2T>>>DR4>>DR5>DR1, whereas in NFPAs, DR2T>>>DR4>>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.
Neto
Leonardo Vieira
LV
Endocrinology Section, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-913, Brazil.
Machado
Evelyn de O
Ede O
Luque
Raul M
RM
Taboada
Giselle F
GF
Marcondes
Jorge B
JB
Chimelli
Leila M C
LM
Quintella
Leonardo Pereira
LP
Niemeyer
Paulo
P
de Carvalho
Denise P
DP
Kineman
Rhonda D
RD
Gadelha
Mônica R
MR
D000172:Acromegaly / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D000236:Adenoma / Q000235:genetics* / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015282:Octreotide / Q000008:administration & dosage / Q000627:therapeutic use*; D010902:Pituitary Gland / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011954:Receptors, Dopamine / Q000235:genetics* / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000235:genetics* / Q000378:metabolism / Q000502:physiology
D003692:Delayed-Action Preparations; D020033:Protein Isoforms; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D017481:Receptors, Somatostatin; D015282:Octreotide