The effects of SOM230 on cell proliferation and adrenocorticotropin secretion in human corticotroph pituitary adenomas.
BACKGROUND
There is no tumor-directed medical therapy available for Cushing's disease.


OBJECTIVE
The objective was to determine the in vitro effect of the somatostatin analog pasireotide (SOM230) on cell proliferation in human corticotroph tumors.


METHODS
Expression of somatostatin receptors (SSTR 1-5) was determined by quantitative RT-PCR in 13 human corticotroph tumors and by immunohistochemistry (IHC) in 12 of the 13 tumors. SOM230 effects on cell proliferation and ACTH release were evaluated in vitro using primary cultures of six of the 13 human corticotroph adenomas.


RESULTS
In our series, we found expression of SSTR subtypes 1, 2, 4, and 5 in human corticotroph tumors by quantitative RT-PCR. All receptor subtypes were detected by IHC, with SSTR subtype 5 having the highest IHC score in 83% (10 of 12) of the cases. Significant suppression of cell proliferation was observed in all tumors cultured (percent suppression range: 10-70%; P = 0.045-0.001). SOM230 inhibited ACTH secretion in five of the six tumors cultured (percent suppression range: 23-56%; P = 0.042-0.001).


CONCLUSIONS
Corticotroph tumors express multiple SSTR subtypes. SOM230 significantly suppressed cell proliferation and ACTH secretion in primary cultures of human corticotroph tumors. These in vitro results support the hypothesis that SOM230 may have a role in the medical therapy of corticotroph tumors.
Batista
Dalia L
DL
Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
Zhang
Xun
X
Gejman
Roger
R
Ansell
Peter J
PJ
Zhou
Yunli
Y
Johnson
Sarah A
SA
Swearingen
Brooke
B
Hedley-Whyte
E Tessa
ET
Stratakis
Constantine A
CA
Klibanski
Anne
A
D049913:ACTH-Secreting Pituitary Adenoma / Q000188:drug therapy*; D000236:Adenoma / Q000188:drug therapy*; D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000328:Adult; D049109:Cell Proliferation / Q000187:drug effects*; D002648:Child; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D047748:Pituitary ACTH Hypersecretion / Q000188:drug therapy; D012333:RNA, Messenger / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000378:metabolism; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D017481:Receptors, Somatostatin; D013004:Somatostatin; D000324:Adrenocorticotropic Hormone; C517782:pasireotide