Somatostatin receptor expression in adrenocortical tumors and effect of a new somatostatin analog SOM230 on hormone secretion in vitro and in ex vivo adrenal cells.
BACKGROUND
Somatostatin is a widely distributed polypeptide that modulates endocrine and exocrine secretion, cell proliferation, and apoptosis by 5 somatostatin receptors (SSTR1-5). The inhibitory effects of somatostatin on tumor growth may be the result of its suppressing the synthesis and/or secretion of growth factors and growth-promoting hormones.


OBJECTIVE
Very little information is available on the effect of somatostatin analogs on adrenal tumors, so we examined SSTR expression in adrenocortical tumors and studied the effect of a somatostatin analog (SOM230) on hormone secretion and cell viability in adrenal cells.


METHODS
SSTR expression was analyzed by real-time PCR in 13 adrenocortical carcinomas (ACC), 24 aldosterone-producing adenomas (APA), 11 cortisol-producing adenomas (CPA), and 7 normal adrenals (NA), and verified by immunohistochemistry (IHC) in 14 samples. The effect of SOM230 on cortisol or aldosterone secretion in H295R and primary cell cultures was determined by radioimmunoassay, and its effect on viability in H295R and SW13 using the MTT test.


RESULTS
SSTR1 and SSTR2 mRNA was expressed in 100% of adrenal tumors. Compared to NA, ACC revealed an increase in almost all SSTR, while only some APA over-expressed SSTR3 and SSTR1. CPA expressed SSTR similar to NA. IHC confirmed the mRNA expression data. At nanomolar concentrations, SOM230 inhibited hormone secretion in primary adrenal cultures and H295R cells, but had no evident effect on cell viability.


CONCLUSIONS
The evidence of SSTR over-expression (particularly in ACC) and of hormone secretion being inhibited by SOM230 suggests a potential therapeutic role for this broad-spectrum somatostatin analog in adrenal tumors.
Endocrinology Division, University of Padua, Via Ospedale 105, 35128 Padua, Italy. barbara.mariniello@unipd.it
B
B
Mariniello
I
I
Finco
P
P
Sartorato
A
A
Patalano
M
M
Iacobone
V
V
Guzzardo
A
A
Fassina
F
F
Mantero
D000236:Adenoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D000306:Adrenal Cortex Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000450:Aldosterone / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D010911:Pituitary Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D017481:Receptors, Somatostatin; D000450:Aldosterone; D013004:Somatostatin; C517782:pasireotide; D006854:Hydrocortisone