Expression and function of somatostatin receptor subtype 1 in human growth hormone secreting pituitary tumors deriving from patients partially responsive or resistant to long-term treatment with somatostatin analogs.
The role of somatostatin (SS) receptor subtype 1 (SSTR(1)) in mediating the inhibitory effect of SS on growth hormone (GH) secreting pituitary tumors has been recently demonstrated. In the present study, we evaluated the effect of the selective SSTR(1) agonist BIM-23745 on in vitro GH secretion in GH-secreting pituitary tumor cells, deriving from patients resistant or partially responsive to octreotide long-acting release (octreotide-LAR) or lanreotide therapy in vivo and expressing SSTR(1) mRNA. In addition, the inhibiting effect of BIM-23745 on the GH secretion was compared with that of octreotide. Our data demonstrate that (1) SSTR(1) receptor was present in 56.25% (9/16) of the GH-secreting adenomas examined; (2) in all GH-secreting pituitary tumors that expressed SSTR(1), BIM-23745 significantly inhibited GH secretion in vitro, and (3) when SSTR(1) subtype was present in tumors from patients resistant to octreotide-LAR or lanreotide therapy, BIM-23745 was able to inhibit the in vitro GH secretion. In conclusion, the results of the current study suggest that SS analogs selective for the SSTR(1) may represent a further useful approach for the treatment of acromegaly in patients resistant or partially responsive to octreotide-LAR or lanreotide treatment in vivo.
Matrone
C
C
Division of Pharmacology, Department of Neuroscience, Federico II University, Naples, Italy.
Pivonello
R
R
Colao
A
A
Cappabianca
P
P
Cavallo
L M
LM
Del Basso De Caro
M L
ML
Taylor
J E
JE
Culler
M D
MD
Lombardi
G
G
Di Renzo
G F
GF
Annunziato
L
L
D000172:Acromegaly / Q000188:drug therapy / Q000378:metabolism*; D000236:Adenoma / Q000188:drug therapy / Q000378:metabolism*; D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005260:Female; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000494:pharmacology / Q000627:therapeutic use; D010456:Peptides, Cyclic / Q000627:therapeutic use; D010911:Pituitary Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D017481:Receptors, Somatostatin / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D010456:Peptides, Cyclic; D017481:Receptors, Somatostatin; C101130:somatostatin receptor type 1; C060347:lanreotide; D019382:Human Growth Hormone; D013004:Somatostatin; D015282:Octreotide